Proposed Changes to the Enzyme List

Accepted name: 3α-hydroxysteroid 3-dehydrogenase (A-specific)

Other name(s): 3β-hydroxy-4β-methylcholestenecarboxylate 3-dehydrogenase (decarboxylating); 3β-hydroxy-4β-methylcholestenoate dehydrogenase; sterol 4α-carboxylic decarboxylase; sterol-4 -carboxylate 3-dehydrogenase (decarboxylating) (ambiguous); ERG26 (gene name); NSDHL (gene name).

Systematic name: 3β-hydroxysteroid-4α-carboxylate:NAD(P)⁺ 3-oxidoreductase (decarboxylating)

Comments: The enzyme catalyses the decarboxylation of the C-4 carbon and the dehydrogenation of a 3β hydroxyl at the C-3 carbon of 3β-hydroxysteroid-4α-carboxylates. It is involved in zymosterol and cholesterol biosynthesis.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 71822-23-6

References:

1. Brady, D.R., Crowder, R.D. and Hayes, W.J. Mixed function oxidases in sterol metabolism. Source of reducing equivalents. J. Biol. Chem. 255 (1980) 10624-10629. [PMID: 7430141]

2. Rahimtula, A.D. and Gaylor, J.L. Partial purification of a microsomal sterol 4α-carboxylic acid decarboxylase. J. Biol. Chem. 247 (1972) 9-15. [PMID: 4401584]

3. Gachotte, D., Barbuch, R., Gaylor, J., Nickel, E. and Bard, M. Characterization of the Saccharomyces cerevisiae ERG26 gene encoding the C-3 sterol dehydrogenase (C-4 decarboxylase) involved in sterol biosynthesis. Proc. Natl. Acad. Sci. USA 95 (1998) 13794-13799. [PMID: 9811880]

4. Caldas, H. and Herman, G.E. NSDHL, an enzyme involved in cholesterol biosynthesis, traffics through the Golgi and accumulates on ER membranes and on the surface of lipid droplets. Hum. Mol. Genet. 12 (2003) 2981-2991. [PMID: 14506130]

[EC 1.1.1.170 created 1978, modified 2002, modified 2012]

*EC 1.1.1.213

Reaction: a 3α-hydroxysteroid + NAD(P)⁺ = a 3-oxosteroid + NAD(P)H + H⁺

Other name(s): 3α-hydroxysteroid dehydrogenase; AKR1C2 (gene name); Akr1c9 (gene name)

Systematic name: 3α-hydroxysteroid:NAD(P)⁺ 3-oxidoreductase (A-specific)

Comments: The enzyme acts on multiple 3α-hydroxysteroids. A-specific with respect to NAD⁺ or NADP⁺ [cf. EC 1.1.1.50, 3α-hydroxysteroid 3-dehydrogenase (B-specific)].

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9028-56-2

References:

1. Björkhem, I. and Danielsson, H. Stereochemistry of hydrogen transfer from pyridine nucleotides catalyzed by Δ⁴-3-oxosteroid 5-β-reductase and 3-α-hydroxysteroid dehydrogenase from rat liver. Eur. J. Biochem. 12 (1970) 80-84. [PMID: 4392180]

2. Tomkins, G.M. A mammalian 3α-hydroxysteroid dehydrogenase. J. Biol. Chem. 218 (1956) 437-447. [PMID: 13278351]

3. Dufort, I., Soucy, P., Labrie, F. and Luu-The, V. Molecular cloning of human type 3 3α-hydroxysteroid dehydrogenase that differs from 20α-hydroxysteroid dehydrogenase by seven amino acids. Biochem. Biophys. Res. Commun. 228 (1996) 474-479. [PMID: 8920937]

4. Nahoum, V., Gangloff, A., Legrand, P., Zhu, D.W., Cantin, L., Zhorov, B.S., Luu-The, V., Labrie, F., Breton, R. and Lin, S.X. Structure of the human 3α-hydroxysteroid dehydrogenase type 3 in complex with testosterone and NADP at 1.25-Å resolution. J. Biol. Chem. 276 (2001) 42091-42098. [PMID: 11514561]

[EC 1.1.1.213 created 1986, modified 2012]

*EC 1.1.1.239

Accepted name: 3α(17β)-hydroxysteroid dehydrogenase (NAD⁺)

Reaction: testosterone + NAD⁺ = androstenedione + NADH + H⁺

Glossary: androstenedione = androst-4-ene-3,17-dione

Other name(s): 3α,17β-hydroxy steroid dehydrogenase; 3α(17β)-HSD; 17-ketoreductase (ambiguous); 17β-HSD (ambiguous); HSD17B6 (gene name); HSD17B8 (gene name)

Systematic name: 3α(or 17β)-hydroxysteroid:NAD⁺ oxidoreductase

Comments: Also acts on other 17β-hydroxysteroids and on the 3α-hydroxy group of pregnanes and bile acids. Different from EC 1.1.1.50 3α-hydroxysteroid dehydrogenase (B-specific) or EC 1.1.1.213 3α-hydroxysteroid dehydrogenase (A-specific).

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 126469-82-7

References:

1. Sweat, M.L., Samuels, L.T. and Lumry, R. Preparation and characterisation of the enzyme which converts testosterone to androstendione. J. Biol. Chem. 185 (1950) 75-84. [PMID: 15436478]

2. Villee, C.A. and Spencer, J.M. Some properties of the pyridine nucleotide-specific 17β-hydroxy steroid dehydrogenase of guinea pig liver. J. Biol. Chem. 235 (1960) 3615-3619. [PMID: 13781425]

3. Endahl, G.L., Kochakia, C.D. and Hamm, D. Separation of a triphosphopyridine nucleotide-specific from a diphosphopyridine-specific 17β-hydroxy (testosterone) dehydrogenase of guinea pig liver. J. Biol. Chem. 235 (1960) 2792-2796. [PMID: 13696735]

4. Ohmura, M., Hara, A., Nakagawa, M. and Sawada, H. Demonstration of 3α(17β)-hydroxysteroid dehydrogenase distinct from 3α-hydroxysteroid dehydrogenase in hamster liver. Biochem. J. 266 (1990) 583-589. [PMID: 2317205]

[EC 1.1.1.239 created 1992, modified 2012 (EC 1.1.1.63 created 1965, incorporated 2012)]

*EC 1.1.1.270

Accepted name: 3β-hydroxysteroid 3-dehydrogenase

Reaction: a 3β-hydroxysteroid + NADP⁺ = a 3-oxosteroid + NADPH + H⁺

Accepted name: UDP-N-acetyl-2-amino-2-deoxyglucuronate dehydrogenase

Other name(s): 3-keto-steroid reductase; 3-KSR; HSD17B7 (gene name); ERG27 (gene name)

Systematic name: 3β-hydroxysteroid:NADP⁺ 3-oxidoreductase

Comments: The enzyme acts on multiple 3β-hydroxysteroids. Participates in the biosynthesis of zemosterol and cholesterol, where it catalyses the reaction in the opposite direction to that shown. The mammalian enzyme is bifunctional and also catalyses EC 1.1.1.62, 17β-estradiol 17-dehydrogenase [4].

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 42616-29-5

References:

1. Swindell, A.C. and Gaylor, J.L. Investigation of the component reactions of oxidative sterol demethylation. Formation and metabolism of 3-ketosteroid intermediates. J. Biol. Chem. 243 (1968) 5546-5555. [PMID: 4387005]

2. Billheimer, J.T., Alcorn, M. and Gaylor, J.L. Solubilization and partial purification of a microsomal 3-ketosteroid reductase of cholesterol biosynthesis. Purification and properties of 3β-hydroxysteroid dehydrogenase and Δ⁵-3-ketosteroid isomerase from bovine corpora lutea. Arch. Biochem. Biophys. 211 (1981) 430-438. [PMID: 6946726]

3. Gachotte, D., Sen, S.E., Eckstein, J., Barbuch, R., Krieger, M., Ray, B.D. and Bard, M. Characterization of the Saccharomyces cerevisiae ERG27 gene encoding the 3-keto reductase involved in C-4 sterol demethylation. Proc. Natl. Acad. Sci. USA 96 (1999) 12655-12660. [PMID: 10535978]

4. Marijanovic, Z., Laubner, D., Moller, G., Gege, C., Husen, B., Adamski, J. and Breitling, R. Closing the gap: identification of human 3-ketosteroid reductase, the last unknown enzyme of mammalian cholesterol biosynthesis. Mol. Endocrinol. 17 (2003) 1715-1725. [PMID: 12829805]

[EC 1.1.1.270 created 2002, modified 2012]

EC 1.1.1.335

Reaction: UDP-2-acetamido-2-deoxy-α-D-glucuronate + NAD⁺ = UDP-2-acetamido-2-deoxy-α-D-ribo-hex-3-uluronate + NADH + H⁺

Accepted name: UDP-N-acetyl-D-mannosamine dehydrogenase

Other name(s): WlbA; WbpB

Systematic name: UDP-N-acetyl-2-amino-2-deoxy-α-D-glucuronate:NAD⁺ 3-oxidoreductase

Comments: This enzyme participates in the biosynthetic pathway for UDP-α-D-ManNAc3NAcA (UDP-2,3-diacetamido-2,3-dideoxy-α-D-mannuronic acid), an important precursor of B-band lipopolysaccharide. The enzymes from Pseudomonas aeruginosa serotype O5 and Thermus thermophilus form a complex with the the enzyme catalysing the next step the pathway (EC 2.6.1.98, UDP-2-acetamido-2-deoxy-ribo-hexuluronate aminotransferase). The enzyme also possesses an EC 1.1.99.2 (2-hydroxyglutarate dehydrogenase) activity, and utilizes the 2-oxoglutarate produced by EC 2.6.1.98 to regenerate the tightly bound NAD⁺. The enzymes from Bordetella pertussis and Chromobacterium violaceum do not bind NAD⁺ as tightly and do not require 2-oxoglutarate to function.

References:

1. Westman, E.L., McNally, D.J., Charchoglyan, A., Brewer, D., Field, R.A. and Lam, J.S. Characterization of WbpB, WbpE, and WbpD and reconstitution of a pathway for the biosynthesis of UDP-2,3-diacetamido-2,3-dideoxy-D-mannuronic acid in Pseudomonas aeruginosa. J. Biol. Chem. 284 (2009) 11854-11862. [PMID: 19282284]

2. Larkin, A. and Imperiali, B. Biosynthesis of UDP-GlcNAc(3NAc)A by WbpB, WbpE, and WbpD: enzymes in the Wbp pathway responsible for O-antigen assembly in Pseudomonas aeruginosa PAO1. Biochemistry 48 (2009) 5446-5455. [PMID: 19348502]

3. Thoden, J.B. and Holden, H.M. Structural and functional studies of WlbA: A dehydrogenase involved in the biosynthesis of 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid. Biochemistry 49 (2010) 7939-7948. [PMID: 20690587]

4. Thoden, J.B. and Holden, H.M. Biochemical and structural characterization of WlbA from Bordetella pertussis and Chromobacterium violaceum: enzymes required for the biosynthesis of 2,3-diacetamido-2,3-dideoxy-D-mannuronic acid. Biochemistry 50 (2011) 1483-1491. [PMID: 21241053]

[EC 1.1.1.335 created 2012]

EC 1.1.1.336

Reaction: UDP-N-acetyl-α-D-mannosamine + 2 NAD⁺ + H₂O = UDP-N-acetyl-α-D-mannosaminuronate + 2 NADH + 2 H⁺

Other name(s): UDP-ManNAc 6-dehydrogenase; wecC (gene name)

Systematic name: UDP-N-acetyl-α-D-mannosamine:NAD⁺ 6-oxidoreductase

Comments: Part of the pathway for acetamido sugar biosynthesis in bacteria and archaea. The enzyme has no activity with NADP⁺.

1. Namboori, S.C. and Graham, D.E. Acetamido sugar biosynthesis in the Euryarchaea. J. Bacteriol. 190 (2008) 2987-2996. [PMID: 18263721]

[EC 1.1.1.336 created 2012]

EC 1.1.1.337

Accepted name: L-2-hydroxycarboxylate dehydrogenase (NAD⁺)

Reaction: a (2S)-2-hydroxycarboxylate + NAD⁺ = a 2-oxocarboxylate + NADH + H⁺

Other name(s): (R)-sulfolactate:NAD⁺ oxidoreductase; L-sulfolactate dehydrogenase; (R)-sulfolactate dehydrogenase; L-2-hydroxyacid dehydrogenase (NAD⁺); ComC

Systematic name: (2S)-2-hydroxycarboxylate:NAD⁺ oxidoreductase

Comments: The enzyme from the archaeon Methanocaldococcus jannaschii acts on multiple L-2-hydroxycarboxylates including (2R)-3-sulfolactate, (S)-malate, (S)-lactate, and (S)-2-hydroxyglutarate [3]. Note that (2R)-3-sulfolactate has the same stereo configuration as (2S)-2-hydroxycarboxylates.

1. Graupner, M., Xu, H. and White, R.H. Identification of an archaeal 2-hydroxy acid dehydrogenase catalyzing reactions involved in coenzyme biosynthesis in methanoarchaea. J. Bacteriol. 182 (2000) 3688-3692. [PMID: 10850983]

2. Graupner, M. and White, R.H. The first examples of (S)-2-hydroxyacid dehydrogenases catalyzing the transfer of the pro-4S hydrogen of NADH are found in the archaea. Biochim. Biophys. Acta 1548 (2001) 169-173. [PMID: 11451450]

3. Graham, D.E. and White, R.H. Elucidation of methanogenic coenzyme biosyntheses: from spectroscopy to genomics. Nat. Prod. Rep. 19 (2002) 133-147. [PMID: 12013276]

4. Rein, U., Gueta, R., Denger, K., Ruff, J., Hollemeyer, K. and Cook, A.M. Dissimilation of cysteate via 3-sulfolactate sulfo-lyase and a sulfate exporter in Paracoccus pantotrophus NKNCYSA. Microbiology 151 (2005) 737-747. [PMID: 15758220]

[EC 1.1.1.337 created 2012]

EC 1.1.1.338

Accepted name: (2R)-3-sulfolactate dehydrogenase (NADP⁺)

Reaction: (2R)-3-sulfolactate + NADP⁺ = 3-sulfopyruvate + NADPH + H⁺

Accepted name: dTDP-6-deoxy-L-talose 4-dehydrogenase (NAD⁺)

Other name(s): (R)-sulfolactate:NADP⁺ oxidoreductase; L-sulfolactate dehydrogenase; (R)-sulfolactate dehydrogenase; ComC

Systematic name: (2R)-3-sulfolactate:NADP⁺ oxidoreductase

Comments: The enzyme from the bacterium Chromohalobacter salexigens can only utilize NADP⁺. It functions both biosynthetically in coenzyme M biosynthesis and degradatively, in the degradation of sulfolactate. It can not use (S)-malate and (S)-lactate.

References:

1. Denger, K. and Cook, A.M. Racemase activity effected by two dehydrogenases in sulfolactate degradation by Chromohalobacter salexigens: purification of (S)-sulfolactate dehydrogenase. Microbiology 156 (2010) 967-974. [PMID: 20007648]

[EC 1.1.1.338 created 2012]

EC 1.1.1.339

Reaction: dTDP-6-deoxy-β-L-talose + NAD⁺ = dTDP-4-dehydro-6-deoxy-β-L-mannose + NADH + H⁺

Other name(s): tll (gene name)

Systematic name: dTDP-6-deoxy-β-L-talose:NAD⁺ 4-oxidoreductase

Comments: The enzyme has been characterized from the bacterium Aggregatibacter actinomycetemcomitans, in which it participates in the biosynthesis of the serotype c-specific polysaccharide antigen. Shows no activity with NADP⁺.

1. Nakano, Y., Suzuki, N., Yoshida, Y., Nezu, T., Yamashita, Y. and Koga, T. Thymidine diphosphate-6-deoxy-L-lyxo-4-hexulose reductase synthesizing dTDP-6-deoxy-L-talose from Actinobacillus actinomycetemcomitans. J. Biol. Chem. 275 (2000) 6806-6812. [PMID: 10702238]

[EC 1.1.1.339 created 2012]

EC 1.1.1.340

Accepted name: 1-deoxy-11β-hydroxypentalenate dehydrogenase

Reaction: 1-deoxy-11β-hydroxypentalenate + NAD⁺ = 1-deoxy-11-oxopentalenate + NADH + H⁺

Accepted name: CDP-abequose synthase

Glossary: 1-deoxy-11β-hydroxypentalenate = (1S,2R,3aR,5aS,8aR)-2-hydroxy-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate

Other name(s): 1-deoxy-11β-hydroxypentalenic acid dehydrogenase; ptlF (gene name); penF (gene name)

Systematic name: 1-deoxy-11β-hydroxypentalenate:NAD⁺ oxidoreductase

Comments: Isolated from the bacterium Streptomyces avermitilis and present in many other Streptomyces species. Part of the pathway for pentalenolactone biosynthesis.

References:

1. You, Z., Omura, S., Ikeda, H. and Cane, D.E. Pentalenolactone biosynthesis: Molecular cloning and assignment of biochemical function to PtlF, a short-chain dehydrogenase from Streptomyces avermitilis, and identification of a new biosynthetic intermediate. Arch. Biochem. Biophys. 459 (2007) 233-240. [PMID: 17178094]

[EC 1.1.1.340 created 2012]

EC 1.1.1.341

Reaction: CDP-α-D-abequose + NADP⁺ = CDP-4-dehydro-3,6-dideoxy-α-D-glucose + NADPH + H⁺

Accepted name: CDP-paratose synthase

Glossary: CDP-α-D-abequose = CDP-3,6-dideoxy-α-D-xylo-hexose

Other name(s): rfbJ (gene name)

Systematic name: CDP-α-D-abequose:NADP⁺ 4-oxidoreductase

Comments: Isolated from Yersinia pseudotuberculosis [1,3] and Salmonella enterica [1,2].

References:

1. Kessler, A.C., Brown, P.K., Romana, L.K. and Reeves, P.R. Molecular cloning and genetic characterization of the rfb region from Yersinia pseudotuberculosis serogroup IIA, which determines the formation of the 3,6-dideoxyhexose abequose. J. Gen. Microbiol. 137 (1991) 2689-2695. [PMID: 1724263]

2. Wyk, P. and Reeves, P. Identification and sequence of the gene for abequose synthase, which confers antigenic specificity on group B salmonellae: homology with galactose epimerase. J. Bacteriol. 171 (1989) 5687-5693. [PMID: 2793832]

3. Thorson, J.S., Lo, S.F., Ploux, O., He, X. and Liu, H.W. Studies of the biosynthesis of 3,6-dideoxyhexoses: molecular cloning and characterization of the asc (ascarylose) region from Yersinia pseudotuberculosis serogroup VA. J. Bacteriol. 176 (1994) 5483-5493. [PMID: 8071227]

[EC 1.1.1.341 created 2012]

EC 1.1.1.342

Reaction: CDP-α-D-paratose + NADP⁺ = CDP-4-dehydro-3,6-dideoxy-α-D-glucose + NADPH + H⁺

Accepted name: 2-hydroxymuconate-6-semialdehyde dehydrogenase

Glossary: CDP-α-D-paratose = CDP-3,6-dideoxy-α-D-glucose = CDP-3,6-dideoxy-α-D-ribo-hexose

Other name(s): rfbS (gene name)

Systematic name: CDP-α-D-paratose:NADP⁺ 4-oxidoreductase

Comments: The enzyme is involved in synthesis of paratose and tyvelose, unusual 3,6-dideoxyhexose sugars that form part of the O-antigen in the lipopolysaccharides of several enteric bacteria. Isolated from Salmonella enterica subsp. enterica serovar Typhi (Salmonella typhi).

References:

1. Verma, N. and Reeves, P. Identification and sequence of rfbS and rfbE, which determine antigenic specificity of group A and group D salmonellae. J. Bacteriol. 171 (1989) 5694-5701. [PMID: 2793833]

2. Hallis, T.M., Lei, Y., Que, N.L. and Liu, H. Mechanistic studies of the biosynthesis of paratose: purification and characterization of CDP-paratose synthase. Biochemistry 37 (1998) 4935-4945. [PMID: 9538012]

[EC 1.1.1.342 created 2012]

[EC 1.2.1.40 Deleted entry: 3α,7α,12α-trihydroxycholestan-26-al 26-oxidoreductase. The activity is part of EC 1.14.13.15, cholestanetriol 26-monooxygenase (EC 1.2.1.40 created 1976, deleted 2012)]

EC 1.2.1.85

Reaction: 2-hydroxymuconate-6-semialdehyde + NAD⁺ + H₂O = (2Z,4E)-2-hydroxyhexa-2,4-dienedioate + NADH + 2 H⁺

Accepted name: geranial dehydrogenase

Glossary: 2-hydroxymuconate-6-semialdehyde = (2E,4Z)-2-hydroxy-6-oxohexa-2,4-dienoate

Other name(s): xylG (gene name); praB (gene name)

Systematic name: (2Z,4E)-2-hydroxy-6-oxohexa-2,4-dienoate:NAD⁺ oxidoreductase

Comments: This substrate for this enzyme is formed by meta ring cleavage of catechol (EC 1.13.11.2, catechol 2,3-dioxygenase), and is an intermediate in the bacterial degradation of several aromatic compounds. Has lower activity with benzaldehyde [1]. Activity with NAD⁺ is more than 10-fold higher than with NADP⁺ [3]. cf. EC 1.2.1.32, aminomuconate-semialdehyde dehydrogenase.

References:

1. Inoue, J., Shaw, J.P., Rekik, M. and Harayama, S. Overlapping substrate specificities of benzaldehyde dehydrogenase (the xylC gene product) and 2-hydroxymuconic semialdehyde dehydrogenase (the xylG gene product) encoded by TOL plasmid pWW0 of Pseudomonas putida. J. Bacteriol. 177 (1995) 1196-1201. [PMID: 7868591]

2. Orii, C., Takenaka, S., Murakami, S. and Aoki, K. Metabolism of 4-amino-3-hydroxybenzoic acid by Bordetella sp. strain 10d: A different modified meta-cleavage pathway for 2-aminophenols. Biosci. Biotechnol. Biochem. 70 (2006) 2653-2661. [PMID: 17090920]

3. Kasai, D., Fujinami, T., Abe, T., Mase, K., Katayama, Y., Fukuda, M. and Masai, E. Uncovering the protocatechuate 2,3-cleavage pathway genes. J. Bacteriol. 191 (2009) 6758-6768. [PMID: 19717587]

[EC 1.2.1.85 created 2012]

EC 1.2.1.86

Reaction: geranial + H₂O + NAD⁺ = geranate + NADH + H⁺

Accepted name: 3-oxo-5α-steroid 4-dehydrogenase (NADP⁺)

Other name(s): GaDH; geoB (gene name)

Systematic name: geranial:NAD⁺ oxidoreductase

Comments: Does not act on neral.

References:

1. Wolken, W.A. and van der Werf, M.J. Geraniol biotransformation-pathway in spores of Penicillium digitatum. Appl. Microbiol. Biotechnol. 57 (2001) 731-737. [PMID: 11778886]

2. Lüddeke, F., Wülfing, A., Timke, M., Germer, F., Weber, J., Dikfidan, A., Rahnfeld, T., Linder, D., Meyerdierks, A. and Harder, J. Geraniol and geranial dehydrogenases induced in anaerobic monoterpene degradation by Castellaniella defragrans. Appl. Environ. Microbiol. 78 (2012) 2128-2136. [PMID: 22286981]

[EC 1.2.1.86 created 2012]

[EC 1.3.1.4 Transferred entry: EC 1.3.1.4, cortisone α-reductase, transferred to EC 1.3.1.22, 3-oxo-5α-steroid 4-dehydrogenase (NADP⁺) (EC 1.3.1.4 created 1965, deleted 2012)]

*EC 1.3.1.22

Reaction: a 3-oxo-5α-steroid + NADP⁺ = a 3-oxo-Δ⁴-steroid + NADPH + H⁺

Other name(s): cholestenone 5α-reductase; testosterone Δ⁴-5α-reductase; steroid 5α-reductase; 3-oxosteroid Δ⁴-dehydrogenase; 5α-reductase; steroid 5α-hydrogenase; 3-oxosteroid 5α-reductase; testosterone Δ⁴-hydrogenase; 4-ene-3-oxosteroid 5α-reductase; reduced nicotinamide adenine dinucleotide phosphate:Δ⁴-3-ketosteroid 5α-oxidoreductase; 4-ene-5α-reductase; Δ⁴-3-ketosteroid 5α-oxidoreductase; cholest-4-en-3-one 5α-reductase; testosterone 5α-reductase; 3-oxo-5α-steroid 4-dehydrogenase

Systematic name: 3-oxo-5α-steroid:NADP⁺ Δ⁴-oxidoreductase

Comments: The enzyme catalyses the conversion of assorted 3-oxo-Δ⁴ steroids into their corresponding 5α form. Substrates for the mammalian enzyme include testosterone, progesterone, and corticosterone. Substrates for the plant enzyme are brassinosteroids such as campest-4-en-3-one and (22α)-hydroxy-campest-4-en-3-one. cf. EC 1.3.99.5, 3-oxo-5α-steroid 4-dehydrogenase (acceptor).

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 37255-34-8

References:

1. Levy, H.R. and Talalay, P. Bacterial oxidation of steroids. II. Studies on the enzymatic mechanisms of ring A dehydrogenation. J. Biol. Chem. 234 (1959) 2014-2021. [PMID: 13673006]

2. Shefer, S., Hauser, S. and Mosbach, E.H. Studies on the biosynthesis of 5α-cholestan-3β-ol. I. Cholestenone 5α-reductase of rat liver. J. Biol. Chem. 241 (1966) 946-952. [PMID: 5907469]

3. Cheng, Y.-J. and Karavolas, H.J. Properties and subcellular distribution of Δ⁴-steroid (progesterone) 5α-reductase in rat anterior pituitary. Steroids 26 (1975) 57-71. [PMID: 1166484]

4. Sargent, N.S. and Habib, F.K. Partial purification of human prostatic 5α-reductase (3-oxo-5α-steroid:NADP⁺ 4-ene-oxido-reductase; EC 1.3.1.22) in a stable and active form. J. Steroid Biochem. Mol. Biol. 38 (1991) 73-77. [PMID: 1705142]

5. Quemener, E., Amet, Y., di Stefano, S., Fournier, G., Floch, H.H. and Abalain, J.H. Purification of testosterone 5α-reductase from human prostate by a four-step chromatographic procedure. Steroids 59 (1994) 712-718. [PMID: 7900170]

6. Poletti, A., Celotti, F., Rumio, C., Rabuffetti, M. and Martini, L. Identification of type 1 5α-reductase in myelin membranes of male and female rat brain. Mol. Cell. Endocrinol. 129 (1997) 181-190. [PMID: 9202401]

7. Li, J., Biswas, M.G., Chao, A., Russell, D.W. and Chory, J. Conservation of function between mammalian and plant steroid 5α-reductases. Proc. Natl. Acad. Sci. USA 94 (1997) 3554-3559. [PMID: 9108014]

8. Rosati, F., Bardazzi, I., De Blasi, P., Simi, L., Scarpi, D., Guarna, A., Serio, M., Racchi, M.L. and Danza, G. 5α-Reductase activity in Lycopersicon esculentum: cloning and functional characterization of LeDET2 and evidence of the presence of two isoenzymes. J. Steroid Biochem. Mol. Biol. 96 (2005) 287-299. [PMID: 15993049]

[EC 1.3.1.22 created 1972, modified 2012]

[EC 1.3.1.30 Transferred entry: EC 1.3.1.30, progesterone 5α-reductase, transferred to EC 1.3.1.22, 3-oxo-5α-steroid 4-dehydrogenase (NADP⁺). (EC 1.3.1.30 created 1978, deleted 2012)]

EC 1.3.1.95

Accepted name: acrylyl-CoA reductase (NADH)

Reaction: propanoyl-CoA + NAD⁺ = acrylyl-CoA + NADH + H⁺

Glossary: propanoyl-CoA = propionyl-CoA

Systematic name: propanoyl-CoA:NAD⁺ oxidoreductase

Comments: Contains FAD. The reaction is catalysed in the opposite direction to that shown. The enzyme from the bacterium Clostridium propionicum is a complex that includes an electron-transfer flavoprotein (ETF). The ETF is reduced by NADH and transfers the electrons to the active site. Catalyses a step in a pathway for L-alanine fermentation to propanoate [1]. cf. EC 1.3.1.84, acrylyl-CoA reductase (NADPH).

References:

1. Hetzel, M., Brock, M., Selmer, T., Pierik, A.J., Golding, B.T. and Buckel, W. Acryloyl-CoA reductase from Clostridium propionicum. An enzyme complex of propionyl-CoA dehydrogenase and electron-transferring flavoprotein. Eur. J. Biochem. 270 (2003) 902-910. [PMID: 12603323]

2. Kandasamy, V., Vaidyanathan, H., Djurdjevic, I., Jayamani, E., Ramachandran, K.B., Buckel, W., Jayaraman, G. and Ramalingam, S. Engineering Escherichia coli with acrylate pathway genes for propionic acid synthesis and its impact on mixed-acid fermentation. Appl. Microbiol. Biotechnol. (2012) . [PMID: 22810300]

[EC 1.3.1.95 created 2012]

EC 1.3.1.96

Accepted name: Botryococcus squalene synthase

Reaction: squalene + diphosphate + NADP⁺ = presqualene diphosphate + NADPH + H⁺

Accepted name: botryococcene synthase

Other name(s): SSL-2 (gene name)

Systematic name: squalene:NADP⁺ oxidoreductase

Comments: Isolated from the green alga Botryococcus braunii BOT22. Acts in the reverse direction. cf. EC 2.5.1.21, squalene synthase, where squalene is formed directly from farnesyl diphosphate.

References:

1. Niehaus, T.D., Okada, S., Devarenne, T.P., Watt, D.S., Sviripa, V. and Chappell, J. Identification of unique mechanisms for triterpene biosynthesis in Botryococcus braunii. Proc. Natl. Acad. Sci. USA 108 (2011) 12260-12265. [PMID: 21746901]

[EC 1.3.1.96 created 2012]

EC 1.3.1.97

Reaction: C₃₀ botryococcene + NADP⁺ + diphosphate = presqualene diphosphate + NADPH + H⁺

Accepted name: pentalenolactone synthase

Glossary: C₃₀ botryococcene = (10S,13R)-10-ethenyl-2,6,10,13,17,21-hexamethyldocosa-2,5,11,16,20-pentaene

Other name(s): SSL-3 (gene name)

Systematic name: C₃₀ botryococcene:NADP⁺ oxidoreductase

Comments: Isolated from the green alga Botryococcus braunii BOT22. Acts in the reverse direction. Involved in the production of botryococcenes, which are triterpenoid hydrocarbons of isoprenoid origin produced in large amount by this alga.

References:

[EC 1.3.1.97 created 2012]

EC 1.3.7.10

Reaction: pentalenolactone F + oxidized ferredoxin = pentalenolactone + reduced ferredoxin

Accepted name: 3-dehydroquinate synthase II

Glossary: pentalenolactone F = (1'R,4'aR,6'aS,9'aR)-8',8'-dimethyl-2'-oxo-4',4'a,6'a,8',9'-hexahydrospiro[oxirane-2,1'-pentaleno[1,6a-c]pyran]-5'-carboxylic acid
pentalenolactone = (1'R,4'aR,6'aR,7'S,9'aS)-7',8'-dimethyl-2'-oxo-4',4'a,6'a,7'-tetrahydrospiro[oxirane-2,1'-pentaleno[1,6a-c]pyran]-5'-carboxylic acid

Other name(s): penM (gene name); pntM (gene name)

Systematic name: pentalenolactone-F:oxidized-ferredoxin oxidoreductase (pentalenolactone forming)

Comments: A heme-thiolate protein (P-450). Isolated from the bacteria Streptomyces exfoliatus and Streptomyces arenae.

References:

1. Zhu, D., Seo, M.J., Ikeda, H. and Cane, D.E. Genome mining in streptomyces. Discovery of an unprecedented P450-catalyzed oxidative rearrangement that is the final step in the biosynthesis of pentalenolactone. J. Am. Chem. Soc. 133 (2011) 2128-2131. [PMID: 21284395]

[EC 1.3.7.10 created 2012]

EC 1.4.1.24

Reaction: 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate + H₂O + NAD⁺ = 3-dehydroquinate + NH₃ + NADP⁺ + H⁺

Accepted name: D-glutamate(D-aspartate) oxidase

Glossary: 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate = 2-amino-2,3,7-trideoxy-D-lyxo-hept-6-ulosonate

Other name(s): DHQ synthase II; MJ1249 (gene name); aroB' (gene name)

Systematic name: 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate:NAD⁺ oxidoreductase (deaminating)

Comments: The enzyme, which was isolated from the archaeon Methanocaldococcus jannaschii, plays a key role in an alternative pathway for the biosynthesis of 3-dehydroquinate (DHQ), an intermediate of the canonical pathway for the biosynthesis of aromatic amino acids. The enzyme catalyses a two-step reaction - an oxidative deamination, followed by cyclization.

References:

1. White, R.H. L-Aspartate semialdehyde and a 6-deoxy-5-ketohexose 1-phosphate are the precursors to the aromatic amino acids in Methanocaldococcus jannaschii. Biochemistry 43 (2004) 7618-7627. [PMID: 15182204]

[EC 1.4.1.24 created 2012]

*EC 1.4.3.15

Reaction: (1) D-glutamate + H₂O + O₂ = 2-oxoglutarate + NH₃ + H₂O₂
(2) D-aspartate + H₂O + O₂ = oxaloacetate + NH₃ + H₂O₂

Other name(s): D-glutamic-aspartic oxidase; D-monoaminodicarboxylic acid oxidase

Systematic name: D-glutamate(D-aspartate):oxygen oxidoreductase (deaminating)

Comments: A flavoprotein (FAD). D-Glutamate and D-aspartate are oxidized at the same rate. Other D-monoaminodicarboxylates, and other D- and L-amino acids, are not oxidized. cf. EC 1.4.3.7, D-glutamate oxidase and EC 1.4.3.1, D-aspartate oxidase.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 9029-20-3

References:

1. Mizushima, S. Purified D-glutamic-aspartic oxidase of Aspergillus ustus. J. Gen. Appl. Microbiol. 3 (1957) 233-239.

[EC 1.4.3.15 created 1983, modified 2012]

EC 1.5.1.43

Accepted name: carboxynorspermidine synthase

Reaction: (1) carboxynorspermidine + H₂O + NADP⁺ = L-aspartate 4-semialdehyde + propane-1,3-diamine + NADPH + H⁺
(2) carboxyspermidine + H₂O + NADP⁺ = L-aspartate 4-semialdehyde + putrescine + NADPH + H⁺

Other name(s): carboxynorspermidine dehydrogenase; carboxyspermidine dehydrogenase; CASDH; CANSDH; VC1624 (gene name)

Systematic name: carboxynorspermidine:NADP⁺ oxidoreductase

Comments: The reaction takes place in the opposite direction. Part of a bacterial polyamine biosynthesis pathway. L-aspartate 4-semialdehyde and propane-1,3-diamine/putrescine form a Schiff base that is reduced to form carboxynorspermidine/carboxyspermidine, respectively [1]. The enzyme from the bacterium Vibrio cholerae is essential for biofilm formation [2]. The enzyme from Campylobacter jejuni only produces carboxyspermidine in vivo even though it also can produce carboxynorspermidine in vitro [3].

1. Nakao, H., Shinoda, S. and Yamamoto, S. Purification and some properties of carboxynorspermidine synthase participating in a novel biosynthetic pathway for norspermidine in Vibrio alginolyticus. J. Gen. Microbiol. 137 (1991) 1737-1742. [PMID: 1955861]

2. Lee, J., Sperandio, V., Frantz, D.E., Longgood, J., Camilli, A., Phillips, M.A. and Michael, A.J. An alternative polyamine biosynthetic pathway is widespread in bacteria and essential for biofilm formation in Vibrio cholerae. J. Biol. Chem. 284 (2009) 9899-9907. [PMID: 19196710]

3. Hanfrey, C.C., Pearson, B.M., Hazeldine, S., Lee, J., Gaskin, D.J., Woster, P.M., Phillips, M.A. and Michael, A.J. Alternative spermidine biosynthetic route is critical for growth of Campylobacter jejuni and is the dominant polyamine pathway in human gut microbiota. J. Biol. Chem. 286 (2011) 43301-43312. [PMID: 22025614]

[EC 1.5.1.43 created 2012]

EC 1.5.1.44

Accepted name: festuclavine dehydrogenase

Reaction: festuclavine + NAD⁺ = 6,8-dimethyl-6,7-didehydroergoline + NADH + H⁺

Glossary: festuclavine = 6,8β-dimethylergoline

Other name(s): FgaFS; festuclavine synthase

Systematic name: festuclavine:NAD⁺ oxidoreductase

Comments: The enzyme participates in the biosynthesis of fumigaclavine C, an ergot alkaloid produced by some fungi of the Trichocomaceae family. The reaction proceeds in vivo in the opposite direction to the one shown here.

1. Wallwey, C., Matuschek, M., Xie, X.L. and Li, S.M. Ergot alkaloid biosynthesis in Aspergillus fumigatus: Conversion of chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS in the presence of the old yellow enzyme FgaOx3. Org. Biomol. Chem. 8 (2010) 3500-3508. [PMID: 20526482]

[EC 1.5.1.44 created 2012]

EC 1.5.1.45

Accepted name: FAD reductase [NAD(P)H]

Reaction: FADH₂ + NAD(P)⁺ = FAD + NAD(P)H + H⁺

Accepted name: hydroxylamine dehydrogenase

Other name(s): GTNG_3158 (gene name)

Systematic name: FADH₂:NAD(P)⁺ oxidoreductase

Comments: This enzyme, isolated from the bacterium Geobacillus thermodenitrificans, participates in the pathway of tryptophan degradation. The enzyme is part of a system that also includes a bifunctional riboflavin kinase/FMN adenylyltransferase and EC 1.14.14.8, anthranilate 3-monooxygenase (FAD). It can reduce either FAD or flavin mononucleotide (FMN) but prefers FAD. The enzyme has a slight preference for NADPH as acceptor. cf. EC 1.5.1.37, FAD reductase (NADH).

References:

1. Liu, X., Dong, Y., Li, X., Ren, Y., Li, Y., Wang, W., Wang, L. and Feng, L. Characterization of the anthranilate degradation pathway in Geobacillus thermodenitrificans NG80-2. Microbiology 156 (2010) 589-595. [PMID: 19942660]

[EC 1.5.1.45 created 2012]

EC 1.7.2.6

Reaction: (1) hydroxylamine + H₂O + 2 ferricytochrome c = nitrite + 2 ferrocytochrome c + 5 H⁺
(2) hydroxylamine + ferricytochrome c = nitric oxide + ferrocytochrome c + 3 H⁺

Other name(s): HAO (ambiguous); hydroxylamine oxidoreductase (ambiguous); hydroxylamine oxidase (misleading)

Systematic name: hydroxylamine:ferricytochrome-c oxidoreductase

Comments: The enzymes from the nitrifying bacterium Nitrosomonas europaea [1,4] and the methylotrophic bacterium Methylococcus capsulatus [5] are hemoproteins with seven c-type hemes and one specialized P-460-type heme per subunit. The enzyme converts hydroxylamine to nitrite via an enzyme-bound nitroxyl intermediate [3]. While nitrite is the main product, the enzyme from Nitrosomonas europaea can produce nitric oxide as well [2].

1. Rees, M. Studies of the hydroxylamine metabolism of Nitrosomonas europaea. I. Purification of hydroxylamine oxidase. Biochemistry 7 (1968) 353-366. [PMID: 5758552]

2. Hooper, A.B. and Terry, K.R. Hydroxylamine oxidoreductase of Nitrosomonas. Production of nitric oxide from hydroxylamine. Biochim. Biophys. Acta 571 (1979) 12-20. [PMID: 497235]

3. Hooper, A.B. and Balny, C. Reaction of oxygen with hydroxylamine oxidoreductase of Nitrosomonas: fast kinetics. FEBS Lett. 144 (1982) 299-303. [PMID: 7117545]

4. Lipscomb, J.D. and Hooper, A.B. Resolution of multiple heme centers of hydroxylamine oxidoreductase from Nitrosomonas. 1. Electron paramagnetic resonance spectroscopy. Biochemistry 21 (1982) 3965-3972. [PMID: 6289867]

5. Poret-Peterson, A.T., Graham, J.E., Gulledge, J. and Klotz, M.G. Transcription of nitrification genes by the methane-oxidizing bacterium, Methylococcus capsulatus strain Bath. ISME J. 2 (2008) 1213-1220. [PMID: 18650926]

[EC 1.7.2.6 created 1972 as EC 1.7.3.4, part transferred 2012 to EC 1.7.2.6]

*EC 1.11.1.8

Accepted name: iodide peroxidase

Reaction: (1) 2 iodide + H₂O₂ + 2 H⁺ = diiodine + 2 H₂O
(2) [thyroglobulin]-L-tyrosine + iodide + H₂O₂ = [thyroglobulin]-3-iodo-L-tyrosine + 2 H₂O
(3) [thyroglobulin]-3-iodo-L-tyrosine + iodide + H₂O₂ = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H₂O
(4) 2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H₂O₂ = [thyroglobulin]-L-thyroxine + [thyroglobulin]-aminoacrylate + 2 H₂O
(5) [thyroglobulin]-3-iodo-L-tyrosine + [thyroglobulin]-3,5-diiodo-L-tyrosine + H₂O₂ = [thyroglobulin]-3,5,3'-triiodo-L-thyronine + [thyroglobulin]-aminoacrylate + 2 H₂O

Glossary: 3,5,3'-triiodo-L-thyronine = triiodo-L-thyronine

Other name(s): thyroid peroxidase; iodotyrosine deiodase; iodinase; iodoperoxidase (heme type); iodide peroxidase-tyrosine iodinase; iodotyrosine deiodinase; monoiodotyrosine deiodinase; thyroperoxidase; tyrosine iodinase; TPO

Systematic name: iodide:hydrogen-peroxide oxidoreductase

Comments: Thyroid peroxidase catalyses the biosynthesis of the thyroid hormones L-thyroxine and triiodo-L-thyronine. It catalyses both the iodination of tyrosine residues in thyroglobulin (forming mono- and di-iodinated forms) and their coupling to form either L-thyroxine or triiodo-L-thyronine.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 9031-28-1

References:

1. Cunningham, B.A. and Kirkwood, S. Enzyme systems concerned with the synthesis of monoiodotyrosine. III. Ion requirements of the soluble system. J. Biol. Chem. 236 (1961) 485-489. [PMID: 13718859]

2. Hosoya, T., Kondo, Y. and Ui, N. Peroxidase activity in thyroid gland and partial purification of the enzyme. J. Biochem. (Tokyo) 52 (1962) 180-189. [PMID: 13964156]

3. Coval, M.L. and Taurog, A. Purification and iodinating activity of hog thyroid peroxidase. J. Biol. Chem. 242 (1967) 5510-5523. [PMID: 12325367]

4. Gavaret, J.M., Cahnmann, H.J. and Nunez, J. Thyroid hormone synthesis in thyroglobulin. The mechanism of the coupling reaction. J. Biol. Chem. 256 (1981) 9167-9173. [PMID: 7021557]

5. Ohtaki, S., Nakagawa, H., Nakamura, M. and Yamazaki, I. One- and two-electron oxidations of tyrosine, monoiodotyrosine, and diiodotyrosine catalyzed by hog thyroid peroxidase. J. Biol. Chem. 257 (1982) 13398-13403. [PMID: 7142155]

6. Magnusson, R.P., Taurog, A. and Dorris, M.L. Mechanism of iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase. J. Biol. Chem. 259 (1984) 197-205. [PMID: 6706930]

7. Virion, A., Courtin, F., Deme, D., Michot, J.L., Kaniewski, J. and Pommier, J. Spectral characteristics and catalytic properties of thyroid peroxidase-H₂O₂ compounds in the iodination and coupling reactions. Arch. Biochem. Biophys. 242 (1985) 41-47. [PMID: 2996435]

8. Rawitch, A.B., Pollock, G., Yang, S.X. and Taurog, A. Thyroid peroxidase glycosylation: the location and nature of the N-linked oligosaccharide units in porcine thyroid peroxidase. Arch. Biochem. Biophys. 297 (1992) 321-327. [PMID: 1497352]

9. Sun, W. and Dunford, H.B. Kinetics and mechanism of the peroxidase-catalyzed iodination of tyrosine. Biochemistry 32 (1993) 1324-1331. [PMID: 8448141]

10. Taurog, A., Dorris, M.L. and Doerge, D.R. Mechanism of simultaneous iodination and coupling catalyzed by thyroid peroxidase. Arch. Biochem. Biophys. 330 (1996) 24-32. [PMID: 8651700]

11. Ruf, J. and Carayon, P. Structural and functional aspects of thyroid peroxidase. Arch. Biochem. Biophys. 445 (2006) 269-277. [PMID: 16098474]

[EC 1.11.1.8 created 1961, modified 2012]

*EC 1.13.11.12

Accepted name: linoleate 13S-lipoxygenase

Reaction: (1) linoleate + O₂ = (9Z,11E,13S)-13-hydroperoxyoctadeca-9,11-dienoate
(2) α-linolenate + O₂ = (9Z,11E,13S,15Z)-13-hydroperoxyoctadeca-9,11,15-trienoate

Glossary: linoleate = (9Z,12Z)-octadeca-9,12-dienoate
α-linolenate = (9Z,12Z,15Z)-octadeca-9,12,15-trienoate

Other name(s): 13-lipoxidase; carotene oxidase; 13-lipoperoxidase; fat oxidase; 13-lipoxydase; lionoleate:O₂ 13-oxidoreductase

Systematic name: linoleate:oxygen 13-oxidoreductase

Comments: Contains nonheme iron. A common plant lipoxygenase that oxidizes linoleate and α-linolenate, the two most common polyunsaturated fatty acids in plants, by inserting molecular oxygen at the C-13 position with (S)-configuration. This enzyme produces precursors for several important compounds, including the plant hormone jasmonic acid. EC 1.13.11.58, linoleate 9S-lipoxygenase, catalyses a similar reaction at the second available position of these fatty acids.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9029-60-1

References:

1. Christopher, J., Pistorius, E. and Axelrod, B. Isolation of an enzyme of soybean lipoxidase. Biochim. Biophys. Acta 198 (1970) 12-19. [PMID: 5461103]

2. Theorell, H., Holman, R.T. and Åkesson, Å. Crystalline lipoxidase. Acta Chem. Scand. 1 (1947) 571-576. [PMID: 18907700]

3. Zimmerman, D.C. Specificity of flaxseed lipoxidase. Lipids 5 (1970) 392-397. [PMID: 5447012]

4. Royo, J., Vancanneyt, G., Perez, A.G., Sanz, C., Stormann, K., Rosahl, S. and Sanchez-Serrano, J.J. Characterization of three potato lipoxygenases with distinct enzymatic activities and different organ-specific and wound-regulated expression patterns. J. Biol. Chem. 271 (1996) 21012-21019. [PMID: 8702864]

5. Bachmann, A., Hause, B., Maucher, H., Garbe, E., Voros, K., Weichert, H., Wasternack, C. and Feussner, I. Jasmonate-induced lipid peroxidation in barley leaves initiated by distinct 13-LOX forms of chloroplasts. Biol. Chem. 383 (2002) 1645-1657. [PMID: 12452441]

[EC 1.13.11.12 created 1961 as EC 1.99.2.1, transferred 1965 to EC 1.13.1.13, transferred 1972 to EC 1.13.11.12, modified 2011, modified 2012]

*EC 1.13.11.35

Accepted name: pyrogallol 1,2-oxygenase

Reaction: 1,2,3-trihydroxybenzene + O₂ = (2Z,4E)-2-hydroxyhexa-2,4-dienedioate

Glossary: (2Z,4E)-2-hydroxyhexa-2,4-dienedioate = (2Z,4E)-2-hydroxymuconate
1,2,3-trihydroxybenzene = pyrogallol

Other name(s): pyrogallol 1,2-dioxygenase

Systematic name: 1,2,3-trihydroxybenzene:oxygen 1,2-oxidoreductase (decyclizing)

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 78310-68-6

References:

1. Groseclose, E.E. and Ribbons, D.W. Metabolism of resorcinylic compounds by bacteria: new pathway for resorcinol catabolism in Azotobacter vinelandii. J. Bacteriol. 146 (1981) 460-466. [PMID: 7217008]

[EC 1.13.11.35 created 1984, modified 2012]

EC 1.13.11.65

Accepted name: carotenoid isomerooxygenase

Reaction: zeaxanthin + O₂ = (3R)-11-cis-3-hydroxyretinal + (3R)-all-trans-3-hydroxyretinal

Accepted name: hydroquinone 1,2-dioxygenase

Other name(s): ninaB (gene name)

Systematic name: zeaxanthin:oxygen 15,15'-oxidoreductase (bond-cleaving, cis-isomerizing)

Comments: The enzyme, characterized from the moth Galleria mellonella and the fruit fly Drosophila melanogaster, is involved in the synthesis of retinal from dietary caroteoids in insects. The enzyme accepts different all-trans carotenoids, including β-carotene, α-carotene and lutein, and catalyses the symmetrical cleavage of the carotenoid and the simultaneous isomerization of only one of the products to a cis configuration. When the substrate is hydroxylated only in one side (as in cryptoxanthin), the enzyme preferentially isomerizes the hydroxylated part of the molecule.

References:

1. Oberhauser, V., Voolstra, O., Bangert, A., von Lintig, J. and Vogt, K. NinaB combines carotenoid oxygenase and retinoid isomerase activity in a single polypeptide. Proc. Natl. Acad. Sci. USA 105 (2008) 19000-19005. [PMID: 19020100]

[EC 1.13.11.65 created 2012 as EC 1.14.13.164, transferred 2012 to EC 1.13.11.65]

EC 1.13.11.66

Reaction: benzene-1,4-diol + O₂ = (2E,4Z)-4-hydroxy-6-oxohexa-2,4-dienoate

Glossary: benzene-1,4-diol = hydroquinone
(2E,4Z)-4-hydroxy-6-oxohexa-2,4-dienoate = 4-hydroxymuconic semialdehyde

Other name(s): hydroquinone dioxygenase

Systematic name: benzene-1,4-diol:oxygen 1,2-oxidoreductase (decyclizing)

Comments: The enzyme is an extradiol-type dioxygenase, and is a member of the nonheme-iron(II)-dependent dioxygenase family. It catalyses the ring cleavage of a wide range of hydroquinone substrates to produce the corresponding 4-hydroxymuconic semialdehydes.

1. Miyauchi, K., Adachi, Y., Nagata, Y. and Takagi, M. Cloning and sequencing of a novel meta-cleavage dioxygenase gene whose product is involved in degradation of γ-hexachlorocyclohexane in Sphingomonas paucimobilis. J. Bacteriol. 181 (1999) 6712-6719. [PMID: 10542173]

2. Moonen, M.J., Synowsky, S.A., van den Berg, W.A., Westphal, A.H., Heck, A.J., van den Heuvel, R.H., Fraaije, M.W. and van Berkel, W.J. Hydroquinone dioxygenase from pseudomonas fluorescens ACB: a novel member of the family of nonheme-iron(II)-dependent dioxygenases. J. Bacteriol. 190 (2008) 5199-5209. [PMID: 18502867]

3. Shen, W., Liu, W., Zhang, J., Tao, J., Deng, H., Cao, H. and Cui, Z. Cloning and characterization of a gene cluster involved in the catabolism of p-nitrophenol from Pseudomonas putida DLL-E4. Bioresour. Technol. 101 (2010) 7516-7522. [PMID: 20466541]

[EC 1.13.11.66 created 2012]

EC 1.13.11.67

Accepted name: 8'-apo-β-carotenoid 14',13'-cleaving dioxygenase

Reaction: 8'-apo-β-carotenol + O₂ = 14'-apo-β-carotenal + an uncharacterized product

Systematic name: 8'-apo-β-carotenol:O₂ oxidoreductase (14',13'-cleaving)

Comments: A thiol-dependent enzyme isolated from rat and rabbit. Unlike EC 1.14.99.36, β-carotene-15,15'-monooxygenase, it is not active towards β-carotene. The secondary product has not been characterized, but may be (3E,5E)-7-hydroxy-6-methylhepta-3,5-dien-2-one.

References:

1. Dmitrovskii, A.A., Gessler, N.N., Gomboeva, S.B., Ershov, Yu.V. and Bykhovsky, V.Ya. Enzymatic oxidation of β-apo-8'-carotenol to β-apo-14'-carotenal by an enzyme different from β-carotene-15,15'-dioxygenase. Biochemistry (Mosc) 62 (1997) 787-792. [PMID: 9331970]

[EC 1.13.11.67 created 2000 as EC 1.13.12.12, transferred 2012 to EC 1.13.11.67]

EC 1.13.11.68

Accepted name: 9-cis-β-carotene 9',10'-cleaving dioxygenase

Reaction: 9-cis-β-carotene + O₂ = 9-cis-10'-apo-β-carotenal + β-ionone

Accepted name: carlactone synthase

Glossary: β-ionone = (3E)-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one

Other name(s): CCD7 (gene name); MAX3 (gene name); NCED7 (gene name)

Systematic name: 9-cis-β-carotene:O₂ oxidoreductase (9',10'-cleaving)

References:

1. Booker, J., Auldridge, M., Wills, S., McCarty, D., Klee, H. and Leyser, O. MAX3/CCD7 is a carotenoid cleavage dioxygenase required for the synthesis of a novel plant signaling molecule. Curr. Biol. 14 (2004) 1232-1238. [PMID: 15268852]

2. Alder, A., Jamil, M., Marzorati, M., Bruno, M., Vermathen, M., Bigler, P., Ghisla, S., Bouwmeester, H., Beyer, P. and Al-Babili, S. The path from β-carotene to carlactone, a strigolactone-like plant hormone. Science 335 (2012) 1348-1351. [PMID: 22422982]

[EC 1.13.11.68 created 2012]

EC 1.13.11.69

Reaction: 9-cis-10'-apo-β-carotenal + 2 O₂ = carlactone + (2E,4E,6E)-7-hydroxy-4-methylhepta-2,4,6-trienal

For diagram of reaction click here and mechanism click here.

Glossary: carlactone = 3-methyl-5-{[(1Z,3E)-2-methyl-4-(2,6,6-trimethylcyclohex-1-en-1-yl)buta-1,3-dien-1-yl]oxy}-5H-furan-2-one

Other name(s): CCD8 (gene name); MAX4 (gene name); NCED8 (gene name)

Systematic name: 9-cis-10'-apo-β-carotenal:O₂ oxidoreductase (14,15-cleaving, carlactone-forming)

Comments: Requires Fe²⁺. The enzyme participates in a pathway leading to biosynthesis of strigolactones, plant hormones involved in promotion of symbiotic associations known as arbuscular mycorrhiza. Also catalyses EC 1.13.11.70, all-trans-10'-apo-β-carotenal 13,14-cleaving dioxygenase, but 10-fold slower. The secondary product has not been characterized, but may be (2E,4E,6E)-7-hydroxy-4-methylhepta-2,4,6-trienal or one of its tautomers. The preferred tautomeric form is not known.

References:

1. Sorefan, K., Booker, J., Haurogne, K., Goussot, M., Bainbridge, K., Foo, E., Chatfield, S., Ward, S., Beveridge, C., Rameau, C. and Leyser, O. MAX4 and RMS1 are orthologous dioxygenase-like genes that regulate shoot branching in Arabidopsis and pea. Genes Dev. 17 (2003) 1469-1474. [PMID: 12815068]

2. Schwartz, S.H., Qin, X. and Loewen, M.C. The biochemical characterization of two carotenoid cleavage enzymes from Arabidopsis indicates that a carotenoid-derived compound inhibits lateral branching. J. Biol. Chem. 279 (2004) 46940-46945. [PMID: 15342640]

3. Alder, A., Jamil, M., Marzorati, M., Bruno, M., Vermathen, M., Bigler, P., Ghisla, S., Bouwmeester, H., Beyer, P. and Al-Babili, S. The path from β-carotene to carlactone, a strigolactone-like plant hormone. Science 335 (2012) 1348-1351. [PMID: 22422982]

[EC 1.13.11.69 created 2012]

EC 1.13.11.70

Accepted name: all-trans-10'-apo-β-carotenal 13,14-cleaving dioxygenase

Reaction: all-trans-10'-apo-β-carotenal + O₂ = 13-apo-β-carotenone + (2E,4E,6E)-4-methylocta-2,4,6-trienedial

Accepted name: carotenoid-9',10'-cleaving dioxygenase

Other name(s): CCD8 (gene name); MAX4 (gene name); NCED8 (gene name)

Systematic name: all-trans-10'-apo-β-carotenal:O₂ oxidoreductase (13,14-cleaving)

Comments: Requires Fe²⁺. The enzyme from the plant Arabidopsis thaliana also catalyses EC 1.13.11.69, carlactone synthase, 10-fold faster.

References:

1. Schwartz, S.H., Qin, X. and Loewen, M.C. The biochemical characterization of two carotenoid cleavage enzymes from Arabidopsis indicates that a carotenoid-derived compound inhibits lateral branching. J. Biol. Chem. 279 (2004) 46940-46945. [PMID: 15342640]

[EC 1.13.11.70 created 2012]

EC 1.13.11.71

Reaction: all-trans-β-carotene + O₂ = all-trans-10'-apo-β-carotenal + β-ionone

Accepted name: 2-hydroxyethylphosphonate dioxygenase

Other name(s): BCO2 (gene name); β-carotene 9',10'-monooxygenase (misleading)

Systematic name: all-trans-β-carotene:O₂ oxidoreductase (9',10'-cleaving)

Comments: Requires Fe²⁺. The enzyme catalyses the asymmetric oxidative cleavage of carotenoids. The mammalian enzyme can also cleave all-trans-lycopene.

References:

1. Kiefer, C., Hessel, S., Lampert, J.M., Vogt, K., Lederer, M.O., Breithaupt, D.E. and von Lintig, J. Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A. J. Biol. Chem. 276 (2001) 14110-14116. [PMID: 11278918]

2. Lindqvist, A., He, Y.G. and Andersson, S. Cell type-specific expression of β-carotene 9',10'-monooxygenase in human tissues. J. Histochem. Cytochem. 53 (2005) 1403-1412. [PMID: 15983114]

[EC 1.13.11.71 created 2012]

EC 1.13.11.72

Reaction: 2-hydroxyethylphosphonate + O₂ = hydroxymethylphosphonate + formate

Accepted name: methylphosphonate synthase

Other name(s): HEPD; phpD (gene name)

Systematic name: 2-hydroxyethylphosphonate:O₂ 1,2-oxidoreductase (hydroxymethylphosphonate forming)

Comments: Requires non-heme-Fe(II). Isolated from some bacteria including Streptomyces hygroscopicus and Streptomyces viridochromogenes. The pro-R hydrogen at C-2 of the ethyl group is retained by the formate ion. Any stereochemistry at C-1 of the ethyl group is lost. One atom from dioxygen is present in each product. Involved in phosphinothricin biosynthesis.

References:

1. Cicchillo, R.M., Zhang, H., Blodgett, J.A., Whitteck, J.T., Li, G., Nair, S.K., van der Donk, W.A. and Metcalf, W.W. An unusual carbon-carbon bond cleavage reaction during phosphinothricin biosynthesis. Nature 459 (2009) 871-874. [PMID: 19516340]

2. Whitteck, J.T., Malova, P., Peck, S.C., Cicchillo, R.M., Hammerschmidt, F. and van der Donk, W.A. On the stereochemistry of 2-hydroxyethylphosphonate dioxygenase. J. Am. Chem. Soc. 133 (2011) 4236-4239. [PMID: 21381767]

3. Peck, S.C., Cooke, H.A., Cicchillo, R.M., Malova, P., Hammerschmidt, F., Nair, S.K. and van der Donk, W.A. Mechanism and substrate recognition of 2-hydroxyethylphosphonate dioxygenase. Biochemistry 50 (2011) 6598-6605. [PMID: 21711001]

[EC 1.13.11.72 created 2012]

EC 1.13.11.73

Reaction: 2-hydroxyethylphosphonate + O₂ = methylphosphonate + HCO₃^-

Accepted name: 1-deoxypentalenic acid 11β-hydroxylase

Other name(s): mpnS (gene name)

Systematic name: 2-hydroxyethylphosphonate:O₂ 1,2-oxidoreductase (methylphosphonate forming)

Comments: Isolated from the marine archaeon Nitrosopumilus maritimus.

References:

1. Metcalf, W.W., Griffin, B.M., Cicchillo, R.M., Gao, J., Janga, S.C., Cooke, H.A., Circello, B.T., Evans, B.S., Martens-Habbena, W., Stahl, D.A. and van der Donk, W.A. Synthesis of methylphosphonic acid by marine microbes: a source for methane in the aerobic ocean. Science 337 (2012) 1104-1107. [PMID: 22936780]

[EC 1.13.11.73 created 2012]

[EC 1.13.12.12 Transferred entry: apo-β-carotenoid-14',13'-dioxygenase. The enzyme was misclassified and has been transferred to EC 1.13.11.67, 8-apo-β-carotenoid 14',13'-cleaving dioxygenase (EC 1.13.12.12 created 2000, modified 2001, deleted 2012)]

EC 1.14.11.35

Reaction: 1-deoxypentalenate + 2-oxoglutarate + O₂ = 1-deoxy-11β-hydroxypentalenate + succinate + CO₂

Accepted name: pentalenolactone F synthase

Glossary: 1-deoxypentalenate = (1R,3aR,5aS,8aR)-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate
1-deoxy-11β-hydroxypentalenate = (1S,2R,3aR,5aS,8aR)-2-hydroxy-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate

Other name(s): ptlH (gene name); sav2991 (gene name); pntH (gene name)

Systematic name: 1-deoxypentalenic acid,2-oxoglutarate:oxygen oxidoreductase

Comments: The enzyme requires Fe(II) and ascorbate. Isolated from the bacterium Streptomyces avermitilis. Part of the pathway for pentalenolactone biosynthesis.

References:

1. You, Z., Omura, S., Ikeda, H. and Cane, D.E. Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlH, a non-heme iron dioxygenase of Streptomyces avermitilis. J. Am. Chem. Soc. 128 (2006) 6566-6567. [PMID: 16704250]

2. You, Z., Omura, S., Ikeda, H., Cane, D.E. and Jogl, G. Crystal structure of the non-heme iron dioxygenase PtlH in pentalenolactone biosynthesis. J. Biol. Chem. 282 (2007) 36552-36560. [PMID: 17942405]

[EC 1.14.11.35 created 2012]

EC 1.14.11.36

Reaction: pentalenolactone D + 2 2-oxoglutarate + 2 O₂ = pentalenolactone F + 2 succinate + 2 CO₂ + H₂O (overall reaction)
(1a) pentalenolactone D + 2-oxoglutarate + O₂ = pentalenolactone E + succinate + CO₂ + H₂O
(1b) pentalenolactone E + 2-oxoglutarate + O₂ = pentalenolactone F + succinate + CO₂

Accepted name: 2-halobenzoate 1,2-dioxygenase

Glossary: pentalenolactone D = (1S,4aR,6aS,9aR)-1,8,8-trimethyl-2-oxo-1,2,4,4a,6a,7,8,9-octahydropentaleno[1,6a-c]pyran-5-carboxylate
pentalenolactone E = (4aR,6aS,9aR)-8,8-dimethyl-1-methylene-2-oxo-1,2,4,4a,6a,7,8,9-octahydropentaleno[1,6a-c]pyran-5-carboxylate
pentalenolactone F = (1'R,4'aR,6'aS,9'aR)-8',8'-dimethyl-2'-oxo-4',4'a,6'a,8',9'-hexahydrospiro[oxirane-2,1'-pentaleno[1,6a-c]pyran]-5'-carboxylic acid

Other name(s): penD (gene name); pntD (gene name); ptlD (gene name)

Systematic name: pentalenolactone-D,2-oxoglutarate:oxygen oxidoreductase

Comments: Requires Fe(II) and ascorbate. Isolated from the bacteria Streptomyces exfoliatus, Streptomyces arenae and Streptomyces avermitilis. Part of the pentalenolactone biosynthesis pathway.

References:

1. Seo, M.J., Zhu, D., Endo, S., Ikeda, H. and Cane, D.E. Genome mining in Streptomyces. Elucidation of the role of Baeyer-Villiger monooxygenases and non-heme iron-dependent dehydrogenase/oxygenases in the final steps of the biosynthesis of pentalenolactone and neopentalenolactone. Biochemistry 50 (2011) 1739-1754. [PMID: 21250661]

[EC 1.14.11.36 created 2012]

*EC 1.14.12.13

Reaction: a 2-halobenzoate + NADH + H⁺ + O₂ = catechol + a halide anion + NAD⁺ + CO₂

For diagram of reaction click here and mechanism click here.

Other name(s): 2-chlorobenzoate 1,2-dioxygenase

Systematic name: 2-halobenzoate,NADH:oxygen oxidoreductase (1,2-hydroxylating, dehalogenating, decarboxylating)

Comments: A multicomponent enzyme system composed of a dioxygenase component and an electron transfer component. The latter contains FAD. The enzyme, characterized from the bacterium Burkholderia cepacia 2CBS, has a broad substrate specificity. Substrates include 2-fluorobenzoate, 2-chlorobenzoate, 2-bromobenzoate, and 2-iodobenzoate, which are processed in this order of preference.

Links to other databases: BRENDA, EXPASY, KEGG, UM-BBD, CAS registry number: 125268-83-9

References:

1. Fetzner, S., Mueller, R. and Lingens, F. Degradation of 2-chlorobenzoate by Pseudomonas cepacia 2CBS. Biol. Chem. Hoppe-Seyler 370 (1989) 1173-1182. [PMID: 2610934]

2. Fetzner, S., Muller, R. and Lingens, F. Purification and some properties of 2-halobenzoate 1,2-dioxygenase, a two-component enzyme system from Pseudomonas cepacia 2CBS. J. Bacteriol. 174 (1992) 279-290. [PMID: 1370284]

3. Haak, B., Fetzner, S. and Lingens, F. Cloning, nucleotide sequence, and expression of the plasmid-encoded genes for the two-component 2-halobenzoate 1,2-dioxygenase from Pseudomonas cepacia 2CBS. J. Bacteriol. 177 (1995) 667-675. [PMID: 7530709]

[EC 1.14.12.13 created 1992, modified 2012]

*EC 1.14.13.15

Accepted name: cholestanetriol 26-monooxygenase

Reaction: 5β-cholestane-3α,7α,12α-triol + 3 NADPH + 3 H⁺ + 3 O₂ = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + 3 NADP⁺ + 4 H₂O (overall reaction)
(1a) 5β-cholestane-3α,7α,12α-triol + NADPH + H⁺ + O₂ = (25R)-5β-cholestane-3α,7α,12α,26-tetraol + NADP⁺ + H₂O
(1b) (25R)-5β-cholestane-3α,7α,12α,26-tetraol + NADPH + H⁺ + O₂ = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + NADP⁺ + 2 H₂O
(1c) (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-al + NADPH⁺ + H⁺ + O₂ = (25R)-3α,7α,12α-trihydroxy-5β-cholestan-26-oate + NADP⁺ + H₂O

Accepted name: L-lysine N⁶-monooxygenase (NADPH)

Other name(s): 5β-cholestane-3α,7α,12α-triol 26-hydroxylase; 5β-cholestane-3α,7α,12α-triol hydroxylase; cholestanetriol 26-hydroxylase; sterol 27-hydroxylase; sterol 26-hydroxylase; cholesterol 27-hydroxylase; CYP27A; CYP27A1; cytochrome P450 27A1'

Systematic name: 5β-cholestane-3α,7α,12α-triol,NADPH:oxygen oxidoreductase (26-hydroxylating)

Comments: The enzyme requires ferredoxin and ferredoxin reductase. It catalyses the first three sterol side chain oxidations in bile acid biosynthesis via the neutral (classic) pathway. Can also act on cholesterol, cholest-5-en-3β,7α-diol, 7α-hydroxycholest-4-en-3-one, and 5β-cholestane-3α,7α-diol. The enzyme can also hydroxylate cholesterol at positions 24 and 25.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 52227-77-7

References:

1. Masui, T., Herman, R. and Staple, E. The oxidation of 5β-cholestane-3α,7α,12α,26-tetraol to 5β-cholestane-3α,7α,12α-triol-26-oic acid via 5β-cholestane-3α,7α,12α-triol-26-al by rat liver. Biochim. Biophys. Acta 117 (1966) 266-268. [PMID: 5914340]

2. Okuda, K. and Hoshita, N. Oxidation of 5β-cholestane-3α,7α,12α-triol by rat-liver mitochondria. Biochim. Biophys. Acta 164 (1968) 381-388. [PMID: 4388637]

3. Wikvall, K. Hydroxylations in biosynthesis of bile acids. Isolation of a cytochrome P-450 from rabbit liver mitochondria catalyzing 26-hydroxylation of C₂₇-steroids. J. Biol. Chem. 259 (1984) 3800-3804. [PMID: 6423637]

4. Andersson, S., Davis, D.L., Dahlbäck, H., Jörnvall, H. and Russell, D.W. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J. Biol. Chem. 264 (1989) 8222-8229. [PMID: 2722778]

5. Dahlback, H. and Holmberg, I. Oxidation of 5β-cholestane-3α,7α,12α-triol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid by cytochrome P-450₂₆ from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 167 (1990) 391-395. [PMID: 2322231]

6. Holmberg-Betsholtz, I., Lund, E., Björkhem, I. and Wikvall, K. Sterol 27-hydroxylase in bile acid biosynthesis. Mechanism of oxidation of 5β-cholestane-3α,7α,12α,27-tetrol into 3α,7α,12α-trihydroxy-5β-cholestanoic acid. J. Biol. Chem. 268 (1993) 11079-11085. [PMID: 8496170]

7. Pikuleva, I.A., Babiker, A., Waterman, M.R. and Bjorkhem, I. Activities of recombinant human cytochrome P450c27 (CYP27) which produce intermediates of alternative bile acid biosynthetic pathways. J. Biol. Chem. 273 (1998) 18153-18160. [PMID: 9660774]

8. Furster, C., Bergman, T. and Wikvall, K. Biochemical characterization of a truncated form of CYP27A purified from rabbit liver mitochondria. Biochem. Biophys. Res. Commun. 263 (1999) 663-666. [PMID: 10512735]

9. Pikuleva, I.A., Puchkaev, A. and Björkhem, I. Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P₄₅₀ 27A1. Biochemistry 40 (2001) 7621-7629. [PMID: 11412116]

[EC 1.14.13.15 created 1976, modified 2005, modified 2012]

*EC 1.14.13.59

Reaction: L-lysine + NADPH + H⁺ + O₂ = N⁶-hydroxy-L-lysine + NADP⁺ + H₂O

Accepted name: 4-nitrocatechol 4-monooxygenase

Other name(s): lysine N⁶-hydroxylase; L-lysine 6-monooxygenase (NADPH) (ambiguous)

Systematic name: L-lysine,NADPH:oxygen oxidoreductase (6-hydroxylating)

Comments: A flavoprotein (FAD). The enzyme from strain EN 222 of Escherichia coli is highly specific for L-lysine; L-ornithine and L-homolysine are, for example, not substrates.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 64295-82-5

References:

1. Plattner, H.J., Pfefferle, P., Romaguera, A., Waschutza, S. and Diekmann, H. Isolation and some properties of lysine N⁶-hydroxylase from Escherichia coli strain EN222. Biol. Met. 2 (1989) 1-5. [PMID: 2518519]

2. Macheroux, P., Plattner, H.J., Romaguera, A. and Diekmann, H. FAD and substrate analogs as probes for lysine N⁶-hydroxylase from Escherichia coli EN 222. Eur. J. Biochem. 213 (1993) 995-1002. [PMID: 8504838]

3. Thariath, A.M., Fatum, K.L., Valvano, M.A. and Viswanatha, T. Physico-chemical characterization of a recombinant cytoplasmic form of lysine: N⁶-hydroxylase. Biochim. Biophys. Acta 1203 (1993) 27-35. [PMID: 8218389]

4. de Lorenzo, V., Bindereif, A., Paw, B.H. and Neilands, J.B. Aerobactin biosynthesis and transport genes of plasmid ColV-K30 in Escherichia coli K-12. J. Bacteriol. 165 (1986) 570-578. [PMID: 2935523]

5. Marrone, L., Siemann, S., Beecroft, M. and Viswanatha, T. Specificity of lysine:N-6-hydroxylase: A hypothesis for a reactive substrate intermediate in the catalytic mechanism. Bioorg. Chem. 24 (1996) 401-406.

6. Goh, C.J., Szczepan, E.W., Menhart, N. and Viswanatha, T. Studies on lysine: N⁶-hydroxylation by cell-free system of Aerobacter aerogenes 62-1. Biochim. Biophys. Acta 990 (1989) 240-245. [PMID: 2493814]

[EC 1.14.13.59 created 1999, modified 2001, modified 2012]

EC 1.14.13.166

Reaction: 4-nitrocatechol + NAD(P)H + H⁺ + O₂ = 2-hydroxy-1,4-benzoquinone + nitrite + NAD(P)⁺ + H₂O

Accepted name: 4-nitrophenol 4-monooxygenase

Systematic name: 4-nitrocatechol,NAD(P)H:oxygen 4-oxidoreductase (4-hydroxylating, nitrite-forming)

Comments: Contains FAD. The enzyme catalyses the oxidation of 4-nitrocatechol with the concomitant removal of the nitro group as nitrite. Forms a two-component system with a flavoprotein reductase [1]. The enzymes from the bacteria Lysinibacillus sphaericus JS905 and Rhodococcus sp. strain PN1 were shown to also catalyse EC 1.14.13.29, 4-nitrophenol 2-monooxygenase [1,2] while the enzyme from Pseudomonas sp. WBC-3 was shown to also catalyse EC 1.14.13.167, 4-nitrophenol 4-monooxygenase [3].

References:

1. Kadiyala, V. and Spain, J.C. A two-component monooxygenase catalyzes both the hydroxylation of p-nitrophenol and the oxidative release of nitrite from 4-nitrocatechol in Bacillus sphaericus JS905. Appl. Environ. Microbiol. 64 (1998) 2479-2484. [PMID: 9647818]

2. Kitagawa, W., Kimura, N. and Kamagata, Y. A novel p-nitrophenol degradation gene cluster from a gram-positive bacterium, Rhodococcus opacus SAO101. J. Bacteriol. 186 (2004) 4894-4902. [PMID: 15262926]

3. Zhang, J.J., Liu, H., Xiao, Y., Zhang, X.E. and Zhou, N.Y. Identification and characterization of catabolic para-nitrophenol 4-monooxygenase and para-benzoquinone reductase from Pseudomonas sp. strain WBC-3. J. Bacteriol. 191 (2009) 2703-2710. [PMID: 19218392]

[EC 1.14.13.166 created 2012]

EC 1.14.13.167

Reaction: 4-nitrophenol + NADPH + H⁺ + O₂ = 1,4-benzoquinone + nitrite + NADP⁺ + H₂O

Accepted name: indole-3-pyruvate monooxygenase

Other name(s): pnpA (gene name); pdcA (gene name)

Systematic name: 4-nitrophenol,NAD(P)H:oxygen 4-oxidoreductase (4-hydroxylating, nitrite-forming)

Comments: Contains FAD. The enzyme catalyses the first step in a degradation pathway for 4-nitrophenol, the oxidation of 4-nitrophenol at position 4 with the concomitant removal of the nitro group as nitrite. The enzyme from the bacterium Pseudomonas sp. strain WBC-3 also catalyses EC 1.14.13.166, 4-nitrocatechol 4-monooxygenase.

References:

1. Zhang, J.J., Liu, H., Xiao, Y., Zhang, X.E. and Zhou, N.Y. Identification and characterization of catabolic para-nitrophenol 4-monooxygenase and para-benzoquinone reductase from Pseudomonas sp. strain WBC-3. J. Bacteriol. 191 (2009) 2703-2710. [PMID: 19218392]

[EC 1.14.13.167 created 2012]

EC 1.14.13.168

Reaction: (indol-3-yl)pyruvate + NADPH + H⁺ + O₂ = (indol-3-yl)acetate + NADP⁺ + H₂O + CO₂

Accepted name: sphinganine C⁴-monooxygenase

Glossary: (indol-3-yl)pyruvate = 3-(1H-indol-3-yl)-2-oxopropanoate
(indol-3-yl)acetate = 2-(1H-indol-3-yl)acetate = indole-3-acetate

Other name(s): YUC2 (gene name); spi1 (gene name)

Systematic name: indole-3-pyruvate,NADPH:oxygen oxidoreductase (1-hydroxylating, decarboxylating)

Comments: This plant enzyme, along with EC 2.6.1.99 L-tryptophan—pyruvate aminotransferase, is responsible for the biosynthesis of the plant hormone indole-3-acetate from L-tryptophan.

References:

1. Mashiguchi, K., Tanaka, K., Sakai, T., Sugawara, S., Kawaide, H., Natsume, M., Hanada, A., Yaeno, T., Shirasu, K., Yao, H., McSteen, P., Zhao, Y., Hayashi, K., Kamiya, Y. and Kasahara, H. The main auxin biosynthesis pathway in Arabidopsis. Proc. Natl. Acad. Sci. USA 108 (2011) 18512-18517. [PMID: 22025724]

2. Zhao, Y. Auxin biosynthesis: a simple two-step pathway converts tryptophan to indole-3-acetic acid in plants. Mol. Plant 5 (2012) 334-338. [PMID: 22155950]

[EC 1.14.13.168 created 2012]

EC 1.14.13.169

Reaction: sphinganine + NADPH + H⁺ + O₂ = phytosphingosine + NADP⁺ + H₂O

Glossary: sphinganine = D-erythro-dihydrosphingosine
phytosphingosine = (4R)-4-hydroxysphinganine

Other name(s): sphingolipid C4-hydroxylase; SUR2 (gene name); SBH1 (gene name); SBH2 (gene name)

Systematic name: sphinganine,NADPH:oxygen oxidoreductase (C⁴-hydroxylating)

Comments: The enzyme is involved in the biosynthesis of sphingolipids in yeast and plants.

1. Haak, D., Gable, K., Beeler, T. and Dunn, T. Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p. J. Biol. Chem. 272 (1997) 29704-29710. [PMID: 9368039]

2. Grilley, M.M., Stock, S.D., Dickson, R.C., Lester, R.L. and Takemoto, J.Y. Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae. J. Biol. Chem. 273 (1998) 11062-11068. [PMID: 9556590]

3. Sperling, P., Ternes, P., Moll, H., Franke, S., Zahringer, U. and Heinz, E. Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis thaliana. FEBS Lett 494 (2001) 90-94. [PMID: 11297741]

[EC 1.14.13.169 created 2012]

EC 1.14.13.170

Accepted name: pentalenolactone D synthase

Reaction: 1-deoxy-11-oxopentalenate + NADPH + H⁺ + O₂ = pentalenolactone D + NADP⁺ + H₂O

Accepted name: neopentalenolactone D synthase

Glossary: 1-deoxy-11-oxopentalenate = (1S,3aR,5aR)-1,7,7-trimethyl-2-oxo-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylic acid
pentalenolactone D = (1S,4aR,6aS,9aR)-1,8,8-trimethyl-2-oxo-1,2,4,4a,6a,7,8,9-octahydropentaleno[1,6a-c]pyran-5-carboxylate

Other name(s): penE (gene name); pntE (gene name)

Systematic name: 1-deoxy-11-oxopentalenate,NADH:oxygen oxidoreductase (pentalenolactone-D forming)

Comments: A FAD-dependent oxygenase. Isolated from the bacteria Streptomyces exfoliatus and Streptomyces arenae. The ketone undergoes a biological Baeyer-Villiger reaction. Part of the pathway of pentalenolactone biosynthesis.

References:

[EC 1.14.13.170 created 2012]

EC 1.14.13.171

Reaction: 1-deoxy-11-oxopentalenate + NADPH + H⁺ + O₂ = neopentalenolactone D + NADP⁺ + H₂O

Accepted name: pentalenic acid synthase

Glossary: 1-deoxy-11-oxopentalenate = (1S,3aR,5aS)-1,7,7-trimethyl-2-oxo-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylic acid
neopentalenolactone D = (1S,4aR,6aS)-1,7,7-trimethyl-3-oxo-4,4a,6a,7,8,9-hexahydro-3H-pentaleno[6a,1-c]pyran-5-carboxylic acid

Other name(s): ptlE (gene name)

Systematic name: 1-deoxy-11-oxopentalenate,NADH:oxygen oxidoreductase (neopentalenolactone-D forming)

Comments: A FAD-dependent oxygenase. Isolated from the bacterium Streptomyces avermitilis. The ketone undergoes a biological Baeyer-Villiger reaction.

References:

[EC 1.14.13.171 created 2012]

EC 1.14.15.11

Reaction: 1-deoxypentalenate + reduced ferredoxin + O₂ = pentalenate + oxidized ferredoxin + H₂O

Accepted name: (+)-larreatricin hydroxylase

Glossary: 1-deoxypentalenate = (1R,3aR,5aS,8aR)-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate
pentalenate = (1R,3aR,5aS,6R,8aS)-6-hydroxy-1,7,7-trimethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene-4-carboxylate

Other name(s): CYP105D7; sav7469 (gene name)

Systematic name: 1-deoxypentalenate,reduced ferredoxin:O₂ oxidoreductase

Comments: A heme-thiolate enzyme (P-450). Isolated from the bacterium Streptomyces avermitilis. The product, pentalenate, is a co-metabolite from pentalenolactone biosynthesis.

References:

1. Takamatsu, S., Xu, L.H., Fushinobu, S., Shoun, H., Komatsu, M., Cane, D.E. and Ikeda, H. Pentalenic acid is a shunt metabolite in the biosynthesis of the pentalenolactone family of metabolites: hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis. J. Antibiot. (Tokyo) 64 (2011) 65-71. [PMID: 21081950]

[EC 1.14.15.11 created 2012]

EC 1.14.99.47

Reaction: (+)-larreatricin + O₂ + AH₂ = (+)-3'-hydroxylarreatricin + A + H₂O

Glossary: (+)-larreatricin = 4,4'-[(2R,3R,4S,5R)-3,4-dimethyltetrahydrofuran-2,5-diyl]bisphenol

Systematic name: (+)-larreatricin:oxygen 3'-hydroxylase

Comments: Isolated from the plant Larrea tridentata (creosote bush). The enzyme has a strong preference for the 3' position of (+)-larreatricin.

1. Cho, M.H., Moinuddin, S.G., Helms, G.L., Hishiyama, S., Eichinger, D., Davin, L.B. and Lewis, N.G. (+)-Larreatricin hydroxylase, an enantio-specific polyphenol oxidase from the creosote bush (Larrea tridentata). Proc. Natl. Acad. Sci. USA 100 (2003) 10641-10646. [PMID: 12960376]

[EC 1.14.99.47 created 2012]

*EC 1.18.1.2

Accepted name: ferredoxin—NADP⁺ reductase

Reaction: 2 reduced ferredoxin + NADP⁺ + H⁺ = 2 oxidized ferredoxin + NADPH

Accepted name: adrenodoxin-NADP⁺ reductase

Other name(s): ferredoxin-nicotinamide adenine dinucleotide phosphate reductase; ferredoxin-NADP⁺ reductase; TPNH-ferredoxin reductase; ferredoxin-NADP⁺ oxidoreductase; NADP⁺:ferredoxin oxidoreductase; ferredoxin-TPN reductase; reduced nicotinamide adenine dinucleotide phosphate-adrenodoxin reductase; ferredoxin-NADP⁺-oxidoreductase; NADPH:ferredoxin oxidoreductase; ferredoxin-nicotinamide-adenine dinucleotide phosphate (oxidized) reductase

Systematic name: ferredoxin:NADP⁺ oxidoreductase

Comments: A flavoprotein (FAD). In chloroplasts and cyanobacteria the enzyme acts on plant-type [2Fe-2S] ferredoxins, but in other bacteria it can also reduce bacterial 2[4Fe-4S] ferredoxins and flavodoxin.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9029-33-8

References:

1. Shin, M., Tagawa, K. and Arnon, D.I. Crystallization of ferredoxin-TPN reductase and its role in the photosynthetic apparatus of chloroplasts. Biochem. Z. 338 (1963) 84-96.

2. Knaff, D.B. and Hirasawa, M. Ferredoxin-dependent chloroplast enzymes. Biochim. Biophys. Acta 1056 (1991) 93-125. [PMID: 1671559]

3. Karplus, P.A., Daniels, M.J. and Herriott, J.R. Atomic structure of ferredoxin-NADP⁺ reductase: prototype for a structurally novel flavoenzyme family. Science 251 (1991) 60-66. [PMID: 1986412]

4. Morales, R., Charon, M.H., Kachalova, G., Serre, L., Medina, M., Gomez-Moreno, C. and Frey, M. A redox-dependent interaction between two electron-transfer partners involved in photosynthesis. EMBO Rep. 1 (2000) 271-276. [PMID: 11256611]

[EC 1.18.1.2 created 1965 as EC 1.6.99.4, transferred 1972 as EC 1.6.7.1, transferred 1978 to EC 1.18.1.2, part transferred 2012 to 1.18.1.6, modified 2012]

EC 1.18.1.6

Reaction: 2 reduced adrenodoxin + NADP⁺ = 2 oxidized adrenodoxin + NADPH + H⁺

Other name(s): adrenodoxin reductase; nicotinamide adenine dinucleotide phosphate-adrenodoxin reductase; AdR; NADPH:adrenal ferredoxin oxidoreductase

Systematic name: adrendoxin:NADP⁺ oxidoreductase

Comments: A flavoprotein (FAD). The enzyme is the first component in the mitochondrial cytochrome P-450 electron transfer systems, and is involved in the biosynthesis of all steroid hormones.

1. Omura, T., Sanders, E., Estabrook, R.W., Cooper, D.Y. and Rosenthal, O. Isolation from adrenal cortex of a nonheme iron protein and a flavoprotein functional as a reduced triphosphopyridine nucleotide-cytochrome P-450 reductase. Arch. Biochem. Biophys. 117 (1966) 660-673.

2. Chu, J.W. and Kimura, T. Studies on adrenal steroid hydroxylases. Molecular and catalytic properties of adrenodoxin reductase (a flavoprotein). J. Biol. Chem. 248 (1973) 2089-2094. [PMID: 4144106]

3. Sugiyama, T. and Yamano, T. Purification and crystallization of NADPH-adrenodoxin reductase from bovine adrenocortical mitochondria. FEBS Lett 52 (1975) 145-148. [PMID: 235468]

4. Hanukoglu, I. and Jefcoate, C.R. Mitochondrial cytochrome P-450_sec. Mechanism of electron transport by adrenodoxin. J. Biol. Chem. 255 (1980) 3057-3061. [PMID: 6766943]

5. Hanukoglu, I. and Hanukoglu, Z. Stoichiometry of mitochondrial cytochromes P-450, adrenodoxin and adrenodoxin reductase in adrenal cortex and corpus luteum. Implications for membrane organization and gene regulation. Eur. J. Biochem. 157 (1986) 27-31. [PMID: 3011431]

6. Hanukoglu, I. and Gutfinger, T. cDNA sequence of adrenodoxin reductase. Identification of NADP-binding sites in oxidoreductases. Eur. J. Biochem. 180 (1989) 479-484. [PMID: 2924777]

7. Ziegler, G.A., Vonrhein, C., Hanukoglu, I. and Schulz, G.E. The structure of adrenodoxin reductase of mitochondrial P450 systems: electron transfer for steroid biosynthesis. J. Mol. Biol. 289 (1999) 981-990. [PMID: 10369776]

[EC 1.18.1.6 created 1965 as EC 1.6.99.4, transferred 1972 as EC 1.6.7.1, transferred 1978 to EC 1.18.1.2, part transferred 2012 to 1.18.1.6]

EC 1.21.3.7

Accepted name: tetrahydrocannabinolic acid synthase

Reaction: cannabigerolate + O₂ = Δ⁹-tetrahydrocannabinolate + H₂O₂

Accepted name: cannabidiolic acid synthase

Glossary: Δ⁹-tetrahydrocannabinolate = Δ⁹-THCA = (6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromene-2-carboxylate
cannabigerolate = CBGA = 3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate
cannabinerolate = 3-[(2Z)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate

Other name(s): THCA synthase; Δ¹-tetrahydrocannabinolic acid synthase

Systematic name: cannabigerolate:oxygen oxidoreductase (cyclizing, Δ⁹-tetrahydrocannabinolate-forming)

Comments: A flavoprotein (FAD). The cofactor is covalently bound. Part of the cannabinoids biosynthetic pathway in the plant Cannabis sativa. The enzyme can also convert cannabinerolate (the (Z)-isomer of cannabigerolate) to Δ⁹-THCA with lower efficiency. The traditional numbering called Δ⁹-tetrahydrocannabinolate, Δ¹-tetrahydrocannabinolate. Systematic peripheral numbering is now recommended.

References:

1. Taura, F., Morimoto, S. Shoyama, Y. and Mechoulam, R. First direct evidence for the mechanism of Δ¹-tetrahydrocannabinolic acid biosynthesis. J. Am. Chem. Soc. 117 (1995) 9766-9767.

2. Sirikantaramas, S., Morimoto, S., Shoyama, Y., Ishikawa, Y., Wada, Y., Shoyama, Y. and Taura, F. The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of Δ¹-tetrahydrocannabinolic acid synthase from Cannabis sativa L. J. Biol. Chem. 279 (2004) 39767-39774. [PMID: 15190053]

3. Shoyama, Y., Takeuchi, A., Taura, F., Tamada, T., Adachi, M., Kuroki, R., Shoyama, Y. and Morimoto, S. Crystallization of Δ¹-tetrahydrocannabinolic acid (THCA) synthase from Cannabis sativa. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 799-801. [PMID: 16511162]

4. Shoyama, Y., Tamada, T., Kurihara, K., Takeuchi, A., Taura, F., Arai, S., Blaber, M., Shoyama, Y., Morimoto, S. and Kuroki, R. Structure and function of 1-tetrahydrocannabinolic acid (THCA) synthase, the enzyme controlling the psychoactivity of Cannabis sativa. J. Mol. Biol. (2012) . [PMID: 22766313]

[EC 1.21.3.7 created 2012]

EC 1.21.3.8

Reaction: cannabigerolate + O₂ = cannabidiolate + H₂O₂

Accepted name: tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase

Glossary: cannabigerolate = CBGA = 3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate
cannabidiolate = 2,4-dihydroxy-3-[(1R,6R)-3-methyl-6-(prop-1-en-2-yl)cyclohex-2-en-1-yl]-6-pentylbenzoate

Other name(s): CBDA synthase

Systematic name: cannabigerolate:oxygen oxidoreductase (cyclizing, cannabidiolate-forming)

Comments: Binds FAD covalently. Part of the cannabinoids biosynthetic pathway of the plant Cannabis sativa. The enzyme can also convert cannabinerolate to cannabidiolate with lower efficiency.

References:

1. Taura, F., Morimoto, S. and Shoyama, Y. Purification and characterization of cannabidiolic-acid synthase from Cannabis sativa L.. Biochemical analysis of a novel enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic acid. J. Biol. Chem. 271 (1996) 17411-17416. [PMID: 8663284]

2. Taura, F., Sirikantaramas, S., Shoyama, Y., Yoshikai, K., Shoyama, Y. and Morimoto, S. Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa. FEBS Lett 581 (2007) 2929-2934. [PMID: 17544411]

[EC 1.21.3.8 created 2012]

*EC 2.1.1.61

Reaction: S-adenosyl-L-methionine + tRNA containing 5-aminomethyl-2-thiouridine = S-adenosyl-L-homocysteine + tRNA containing 5-methylaminomethyl-2-thiouridylate

Other name(s): transfer ribonucleate 5-methylaminomethyl-2-thiouridylate 5-methyltransferase; tRNA 5-methylaminomethyl-2-thiouridylate 5'-methyltransferase

Systematic name: S-adenosyl-L-methionine:tRNA (5-methylaminomethyl-2-thio-uridylate)-methyltransferase

Comments: This enzyme is specific for the terminal methyl group of 5-methylaminomethyl-2-thiouridylate.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 39391-17-8

References:

1. Taya, Y. and Nishimura, S. Biosynthesis of 5-methylaminomethyl-2-thiouridylate. I. Isolation of a new tRNA-methylase specific for 5-methylaminomethyl-2-thiouridylate. Biochem. Biophys. Res. Commun. 51 (1973) 1062-1068. [PMID: 4703553]

2. Taya, Y. and Nishimura, S. In: Salvatore, F., Borek, E., Zappia, V., Williams-Ashman, H.G. and Schlenk, F. (Eds), The Biochemistry of Adenosylmethionine, Columbia University Press, New York, 1977, p. 251.

[EC 2.1.1.61 created 1982, modified 2012]

EC 2.1.1.260

Accepted name: rRNA small subunit pseudouridine methyltransferase Nep1

Reaction: S-adenosyl-L-methionine + pseudouridine¹¹⁹¹ in yeast 18S rRNA = S-adenosyl-L-homocysteine + N¹-methylpseudouridine¹¹⁹¹ in yeast 18S rRNA

Other name(s): Nep1; nucleolar essential protein 1

Systematic name: S-adenosyl-L-methionine:18S rRNA (pseudouridine¹¹⁹¹-N¹)-methyltransferase

Comments: This enzyme, which occurs in both prokaryotes and eukaryotes, recognizes specific pseudouridine residues (Ψ) in small subunits of ribosomal RNA based on the local RNA structure. It recognizes Ψ⁹¹⁴ in 16S rRNA from the archaeon Methanocaldococcus jannaschii, Ψ¹¹⁹¹ in yeast 18S rRNA, and Ψ¹²⁴⁸ in human 18S rRNA.

1. Taylor, A.B., Meyer, B., Leal, B.Z., Kötter, P., Schirf, V., Demeler, B., Hart, P.J., Entian, K.-D. and Wöhnert, J. The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site. Nucleic Acids Res. 36 (2008) 1542-1554. [PMID: 18208838]

2. Wurm, J.P., Meyer, B., Bahr, U., Held, M., Frolow, O., Kötter, P., Engels, J.W., Heckel, A., Karas, M., Entian, K.-D. and Wöhnert, J. The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N¹-specific methyltransferase. Nucleic Acids Res. 38 (2010) 2387-2398. [PMID: 20047967]

3. Meyer, B., Wurm, J.P., Kötter, P., Leisegang, M.S., Schilling, V., Buchhaupt, M., Held, M., Bahr, U., Karas, M., Heckel, A., Bohnsack, M.T., Wöhnert, J. and Entian, K.-D. The Bowen-Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Ψ¹¹⁹¹ in yeast 18S rRNA. Nucleic Acids Res. 39 (2011) 1526-1537. [PMID: 20972225]

[EC 2.1.1.260 created 2012]

EC 2.1.1.261

Accepted name: 4-dimethylallyltryptophan N-methyltransferase

Reaction: S-adenosyl-L-methionine + 4-dimethylallyl-L-tryptophan = S-adenosyl-L-homocysteine + 4-dimethylallyl-L-abrine

Glossary: 4-dimethylallyl-L-tryptophan = 4-(3-methylbut-2-enyl)-L-tryptophan
4-dimethylallyl-L-abrine = 4-(3-methylbut-2-enyl)-L-abrine

Other name(s): fgaMT (gene name); easE (gene name)

Systematic name: S-adenosyl-L-methionine:4-(3-methylbut-2-enyl)-L-tryptophan N-methyltransferase

Comments: The enzyme catalyses a step in the pathway leading to biosynthesis of ergot alkaloids in certain fungi.

1. Rigbers, O. and Li, S.M. Ergot alkaloid biosynthesis in Aspergillus fumigatus. Overproduction and biochemical characterization of a 4-dimethylallyltryptophan N-methyltransferase. J. Biol. Chem. 283 (2008) 26859-26868. [PMID: 18678866]

[EC 2.1.1.261 created 2012]

EC 2.1.1.262

Accepted name: squalene methyltransferase

Reaction: 2 S-adenosyl-L-methionine + squalene = 2 S-adenosyl-L-homocysteine + 3,22-dimethyl-1,2,23,24-tetradehydro-2,3,22,23-tetrahydrosqualene (overall reaction)
(1a) S-adenosyl-L-methionine + squalene = S-adenosyl-L-homocysteine + 3-methyl-1,2-didehydro-2,3-dihydrosqualene
(1b) S-adenosyl-L-methionine + 3-methyl-1,2-didehydro-2,3-dihydrosqualene = S-adenosyl-L-homocysteine + 3,22-dimethyl-1,2,23,24-tetradehydro-2,3,22,23-tetrahydrosqualene

Accepted name: botryococcene C-methyltransferase

Other name(s): TMT-1; TMT-2

Systematic name: S-adenosyl-L-methionine:squalene C-methyltransferase

Comments: Two isoforms differing in their specificity were isolated from the green alga Botryococcus braunii BOT22. TMT-1 gave more of the dimethylated form whereas TMT2 gave more of the monomethylated form.

References:

1. Niehaus, T.D., Kinison, S., Okada, S., Yeo, Y.S., Bell, S.A., Cui, P., Devarenne, T.P. and Chappell, J. Functional identification of triterpene methyltransferases from Botryococcus braunii race B. J. Biol. Chem. 287 (2012) 8163-8173. [PMID: 22241476]

[EC 2.1.1.262 created 2012]

EC 2.1.1.263

Reaction: 2 S-adenosyl-L-methionine + C₃₀ botryococcene = 2 S-adenosyl-L-homocysteine + 3,20-dimethyl-1,2,21,22-tetradehydro-2,3,20,21-tetrahydrobotryococcene (overall reaction)
(1a) S-adenosyl-L-methionine + C₃₀ botryococcene = S-adenosyl-L-homocysteine + 3-methyl-1,2-didehydro-2,3-dihydrobotryococcene
(1b) S-adenosyl-L-methionine + 3-methyl-1,2-didehydro-2,3-dihydrobotryococcene = S-adenosyl-L-homocysteine + 3,20-dimethyl-1,2,21,22-tetradehydro-2,3,20,21-tetrahydrobotryococcene
(2a) S-adenosyl-L-methionine + C₃₀ botryococcene = S-adenosyl-L-homocysteine + 20-methyl-21,22-didehydro-20,21-dihydrobotryococcene
(2b) S-adenosyl-L-methionine + 20-methyl-21,22-didehydro-20,21-dihydrobotryococcene = S-adenosyl-L-homocysteine + 3,20-dimethyl-1,2,21,22-tetradehydro-2,3,20,21-tetrahydrobotryococcene

Accepted name: 23S rRNA (guanine²⁰⁶⁹-N⁷)-methyltransferase

Glossary: C₃₀ botryococcene = (10S,13R)-10-ethenyl-2,6,10,13,17,21-hexamethyldocosa-2,5,11,16,20-pentaene
3-methyl-1,2-didehydro-2,3-dihydrobotryococcene = showacene
20-methyl-21,22-didehydro-20,21-dihydrobotryococcene = isoshowacene

Other name(s): TMT-3

Systematic name: S-adenosyl-L-methionine:botryococcene C-methyltransferase

Comments: Isolated from the green alga Botryococcus braunii BOT22. Shows a very weak activity with squalene.

References:

[EC 2.1.1.263 created 2012]

EC 2.1.1.264

Reaction: S-adenosyl-L-methionine + guanine²⁰⁶⁹ in 23S rRNA = S-adenosyl-L-homocysteine + N⁷-methylguanine²⁰⁶⁹ in 23S rRNA

Other name(s): rlmK (gene name); 23S rRNA m⁷G²⁰⁶⁹ methyltransferase

Systematic name: S-adenosyl-L-methionine:23S rRNA (guanine²⁰⁶⁹-N⁷)-methyltransferase

Comments: The enzyme specifically methylates guanine²⁰⁶⁹ at position N7 in 23S rRNA. In γ-proteobacteria the enzyme also catalyses EC 2.1.1.173, 23S rRNA (guanine²⁴⁴⁵-N²)-methyltransferase, while in β-proteobacteria the activities are carried out by separate proteins [1]. The enzyme from the γ-proteobacterium Escherichia coli has RNA unwinding activity as well [1].

References:

1. Kimura, S., Ikeuchi, Y., Kitahara, K., Sakaguchi, Y., Suzuki, T. and Suzuki, T. Base methylations in the double-stranded RNA by a fused methyltransferase bearing unwinding activity. Nucleic Acids Res. 40 (2012) 4071-4085. [PMID: 22210896]

[EC 2.1.1.264 created 2012]

EC 2.1.1.265

Accepted name: tellurite methyltransferase

Reaction: S-adenosyl-L-methionine + tellurite = S-adenosyl-L-homocysteine + methanetelluronate

Other name(s): TehB

Systematic name: S-adenosyl-L-methionine:tellurite methyltransferase

Comments: The enzyme is involved in the detoxification of tellurite. It can also methylate selenite and selenium dioxide.

1. Liu, M., Turner, R.J., Winstone, T.L., Saetre, A., Dyllick-Brenzinger, M., Jickling, G., Tari, L.W., Weiner, J.H. and Taylor, D.E. Escherichia coli TehB requires S-adenosylmethionine as a cofactor to mediate tellurite resistance. J. Bacteriol. 182 (2000) 6509-6513. [PMID: 11053398]

2. Choudhury, H.G., Cameron, A.D., Iwata, S. and Beis, K. Structure and mechanism of the chalcogen-detoxifying protein TehB from Escherichia coli. Biochem. J. 435 (2011) 85-91. [PMID: 21244361]

[EC 2.1.1.265 created 2012]

*EC 2.3.1.177

Accepted name: 3,5-dihydroxybiphenyl synthase

Reaction: 3 malonyl-CoA + benzoyl-CoA = 4 CoA + 3,5-dihydroxybiphenyl + 4 CO₂

Other name(s): BIS1; biphenyl synthase (ambiguous)

Systematic name: malonyl-CoA:benzoyl-CoA malonyltransferase

Comments: A polyketide synthase that is involved in the production of the phytoalexin aucuparin. 2-Hydroxybenzoyl-CoA can also act as substrate but it leads to the derailment product 4-hydroxycoumarin (cf. EC 2.3.1.208, 4-hydroxycoumarin synthase) [2]. This enzyme uses the same starter substrate as EC 2.3.1.151, benzophenone synthase.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 1217551-24-0

References:

1. Liu, B., Beuerle, T., Klundt, T. and Beerhues, L. Biphenyl synthase from yeast-extract-treated cell cultures of Sorbus aucuparia. Planta 218 (2004) 492-496. [PMID: 14595561]

2. Liu, B., Raeth, T., Beuerle, T. and Beerhues, L. Biphenyl synthase, a novel type III polyketide synthase. Planta 225 (2007) 1495-1503. [PMID: 17109150]

[EC 2.3.1.177 created 2006, modified 2012]

EC 2.3.1.204

Accepted name: octanoyl-[GcvH]:protein N-octanoyltransferase

Reaction: [glycine cleavage system H]-N⁶-octanoyl-L-lysine + a [lipoyl-carrier protein] = glycine cleavage system H + a [lipoyl-carrier protein]-N⁶-octanoyl-L-lysine

Glossary: GcvH = glycine cleavage system H]

Other name(s): LipL; octanoyl-[GcvH]:E2 amidotransferase; ywfL (gene name)

Systematic name: [glycine cleavage system H]-N⁶-octanoyl-L-lysine:[lipoyl-carrier protein]-N⁶-L-lysine octanoyltransferase

Comments: In the bacterium Bacillus subtilis it has been shown that the enzyme catalyses the amidotransfer of the octanoyl moiety from [glycine cleavage system H]-N⁶-octanoyl-L-lysine (i.e. octanoyl-GcvH) to the E2 subunit (dihydrolipoamide acetyltransferase) of pyruvate dehydrogenase.

1. Christensen, Q.H., Martin, N., Mansilla, M.C., de Mendoza, D. and Cronan, J.E. A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis. Mol. Microbiol. 80 (2011) 350-363. [PMID: 21338421]

2. Martin, N., Christensen, Q.H., Mansilla, M.C., Cronan, J.E. and de Mendoza, D. A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis. Mol. Microbiol. 80 (2011) 335-349. [PMID: 21338420]

[EC 2.3.1.204 created 2012]

EC 2.3.1.205

Accepted name: fumigaclavine B O-acetyltransferase

Reaction: acetyl-CoA + fumigaclavine B = CoA + fumigaclavine A

Glossary: fumigaclavine B = 6,8β-dimethylergolin-9-ol
fumigaclavine A = 6,8β-dimethylergolin-9β-yl acetate

Other name(s): FgaAT

Systematic name: acetyl-CoA:fumigaclavine B O-acetyltransferase

Comments: The enzyme participates in the biosynthesis of fumigaclavine C, an ergot alkaloid produced by some fungi of the Trichocomaceae family.

1. Liu, X., Wang, L., Steffan, N., Yin, W.B. and Li, S.M. Ergot alkaloid biosynthesis in Aspergillus fumigatus: FgaAT catalyses the acetylation of fumigaclavine B. ChemBioChem. 10 (2009) 2325-2328. [PMID: 19672909]

[EC 2.3.1.205 created 2012]

EC 2.3.1.206

Accepted name: 3,5,7-trioxododecanoyl-CoA synthase

Reaction: 3 malonyl-CoA + hexanoyl-CoA = 3 CoA + 3,5,7-trioxododecanoyl-CoA + 3 CO₂

Accepted name: β-ketodecanoyl-[acyl-carrier-protein] synthase

Other name(s): TKS (ambiguous); olivetol synthase (incorrect)

Systematic name: malonyl-CoA:hexanoyl-CoA malonyltransferase (3,5,7-trioxododecanoyl-CoA-forming)

Comments: A polyketide synthase catalysing the first committed step in the cannabinoids biosynthetic pathway of the plant Cannabis sativa. The enzyme was previously thought to also function as a cyclase, but the cyclization is now known to be catalysed by EC 4.4.1.26, olivetolic acid cyclase.

References:

1. Taura, F., Tanaka, S., Taguchi, C., Fukamizu, T., Tanaka, H., Shoyama, Y. and Morimoto, S. Characterization of olivetol synthase, a polyketide synthase putatively involved in cannabinoid biosynthetic pathway. FEBS Lett 583 (2009) 2061-2066. [PMID: 19454282]

2. Gagne, S.J., Stout, J.M., Liu, E., Boubakir, Z., Clark, S.M. and Page, J.E. Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc. Natl. Acad. Sci. USA 109 (2012) 12811-12816. [PMID: 22802619]

[EC 2.3.1.206 created 2012]

EC 2.3.1.207

Reaction: octanoyl-CoA + a malonyl-[acyl-carrier protein] = a 3-oxodecanoyl-[acyl-carrier protein] + CoA + CO₂

Glossary: [acyl-carrier protein] = [acp]

Systematic name: octanoyl-CoA:malonyl-[acyl-carrier protein] C-heptanoylltransferase (decarboxylating, CoA-forming)

Comments: This enzyme, which has been characterized from the bacterium Pseudomonas aeruginosa PAO1, catalyses the condensation of octanoyl-CoA, obtained from exogenously supplied fatty acids via β-oxidation, with malonyl-[acp], forming 3-oxodecanoyl-[acp], an intermediate of the fatty acid elongation cycle. The enzyme provides a shunt for β-oxidation degradation intermediates into de novo fatty acid biosynthesis.

1. Yuan, Y., Leeds, J.A. and Meredith, T.C. Pseudomonas aeruginosa directly shunts β-oxidation degradation intermediates into de novo fatty acid biosynthesis. J. Bacteriol. (2012) . [PMID: 22753057]

[EC 2.3.1.207 created 2012]

EC 2.3.1.208

Accepted name: 4-hydroxycoumarin synthase

Reaction: malonyl-CoA + 2-hydroxybenzoyl-CoA = 2 CoA + 4-hydroxycoumarin + CO₂

Glossary: 2-hydroxybenzoyl-CoA = salicyloyl-coA

Other name(s): BIS2; BIS3

Systematic name: malonyl-CoA:2-hydroxybenzoyl-CoA malonyltransferase

Comments: The enzyme, a polyketide synthase, can also accept benzoyl-CoA as substrate, which it condenses with 3 malonyl-CoA molecules to form 3,5-dihydroxybiphenyl (cf. EC 2.3.1.177, biphenyl synthase) [1].

References:

1. Liu, B., Raeth, T., Beuerle, T. and Beerhues, L. A novel 4-hydroxycoumarin biosynthetic pathway. Plant Mol. Biol. 72 (2010) 17-25. [PMID: 19757094]

[EC 2.3.1.208 created 2012]

EC 2.3.1.209

Accepted name: dTDP-4-amino-4,6-dideoxy-D-glucose acyltransferase

Reaction: acetyl-CoA + dTDP-4-amino-4,6-dideoxy-α-D-glucose = CoA + dTDP-4-acetamido-4,6-dideoxy-α-D-glucose

Other name(s): VioB

Systematic name: acetyl-CoA:dTDP-4-amino-4,6-dideoxy-α-D-glucose N-acetyltransferase

Comments: The non-activated product, 4-acetamido-4,6-dideoxy-α-D-glucose, is part of the O antigens of Shigella dysenteriae type 7 and Escherichia coli O7.

1. Wang, Y., Xu, Y., Perepelov, A.V., Qi, Y., Knirel, Y.A., Wang, L. and Feng, L. Biochemical characterization of dTDP-D-Qui4N and dTDP-D-Qui4NAc biosynthetic pathways in Shigella dysenteriae type 7 and Escherichia coli O7. J. Bacteriol. 189 (2007) 8626-8635. [PMID: 17905981]

[EC 2.3.1.209 created 2012]

EC 2.3.1.210

Accepted name: dTDP-4-amino-4,6-dideoxy-D-galactose acyltransferase

Reaction: acetyl-CoA + dTDP-4-amino-4,6-dideoxy-α-D-galactose = CoA + dTDP-4-acetamido-4,6-dideoxy-α-D-galactose

Glossary: dTDP-4-amino-4,6-dideoxy-α-D-galactose = dTDP-α-D-fucosamine

Other name(s): TDP-fucosamine acetyltransferase; WecD; RffC

Systematic name: acetyl-CoA:dTDP-4-amino-4,6-dideoxy-α-D-galactose N-acetyltransferase

Comments: The product, TDP-4-acetamido-4,6-dideoxy-D-galactose, is utilized in the biosynthesis of Enterobacterial Common Antigen (ECA).

1. Hung, M.N., Rangarajan, E., Munger, C., Nadeau, G., Sulea, T. and Matte, A. Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis. J. Bacteriol. 188 (2006) 5606-5617. [PMID: 16855251]

[EC 2.3.1.210 created 2012]

[EC 2.4.1.119 Transferred entry: dolichyl-diphosphooligosaccharideprotein glycotransferase. As the enzyme transfers more than one hexosyl group, it has been transferred to EC 2.4.99.18, dolichyl-diphosphooligosaccharideprotein glycotransferase (EC 2.4.1.119 created 1984, deleted 2012)]

EC 2.4.1.289

Accepted name: N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase

Reaction: dTDP-6-deoxy-β-L-mannose + N-acetyl-α-D-glucosaminyl-diphospho-trans,octacis-decaprenol = dTDP + α-L-rhamnopyranosyl-(1→3)-N-acetyl-α-D-glucosaminyl-diphospho-trans,octacis-decaprenol

Glossary: dTDP-6-deoxy-β-L-mannose = dTDP-4-β-L-rhamnose

Other name(s): WbbL

Systematic name: dTDP-6-deoxy-β-L-mannose:N-acetyl-α-D-glucosaminyl-diphospho-trans,octacis-decaprenol 3-α-L-rhamnosyltransferase

Comments: Requires Mn²⁺ or Mg²⁺. Isolated from Mycobacterium smegmatis [1] and Mycobacterium tuberculosis [2]. The enzyme catalyses the addition of a rhamnosyl unit to N-acetyl-α-D-glucosaminyl-diphospho-trans,octacis-decaprenol, completing the synthesis of the linkage unit that attaches the arabinogalactan moiety to the peptidoglycan moiety in Mycobacterial cell wall.

1. Mills, J.A., Motichka, K., Jucker, M., Wu, H.P., Uhlik, B.C., Stern, R.J., Scherman, M.S., Vissa, V.D., Pan, F., Kundu, M., Ma, Y.F. and McNeil, M. Inactivation of the mycobacterial rhamnosyltransferase, which is needed for the formation of the arabinogalactan-peptidoglycan linker, leads to irreversible loss of viability. J. Biol. Chem. 279 (2004) 43540-43546. [PMID: 15294902]

2. Grzegorzewicz, A.E., Ma, Y., Jones, V., Crick, D., Liav, A. and McNeil, M.R. Development of a microtitre plate-based assay for lipid-linked glycosyltransferase products using the mycobacterial cell wall rhamnosyltransferase WbbL. Microbiology 154 (2008) 3724-3730. [PMID: 19047740]

[EC 2.4.1.289 created 2012]

EC 2.4.1.290

Accepted name: N,N'-diacetylbacillosaminyl-diphospho-undecaprenol α-1,3-N-acetylgalactosaminyltransferase

Reaction: UDP-N-acetyl-α-D-galactosamine + N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol = UDP + N-acetyl-D-galactosaminyl-α-(1→3)-N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol

Accepted name: N-acetylgalactosamine-N,N'-diacetylbacillosaminyl-diphospho-undecaprenol 4-α-N-acetylgalactosaminyltransferase

Glossary: N,N'-diacetyl-D-bacillosamine = 2,4-diacetamido-2,4,6-trideoxy-D-glucopyranose

Other name(s): PglA

Systematic name: UDP-N-acetyl-α-D-galactosamine:N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol 3-α-N-acetyl-D-galactosaminyltransferase

Comments: Isolated from Campylobacter jejuni. Part of a bacterial N-linked glycosylation pathway.

References:

1. Glover, K.J., Weerapana, E. and Imperiali, B. In vitro assembly of the undecaprenylpyrophosphate-linked heptasaccharide for prokaryotic N-linked glycosylation. Proc. Natl. Acad. Sci. USA 102 (2005) 14255-14259. [PMID: 16186480]

[EC 2.4.1.290 created 2012]

EC 2.4.1.291

Reaction: UDP-N-acetyl-α-D-galactosamine + N-acetyl-D-galactosaminyl-α-(1→3)-N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol = UDP + N-acetyl-D-galactosaminyl-α-(1→4)-N-acetyl-D-galactosaminyl-α-(1→3)-N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol

Accepted name: GalNAc-α-(1→4)-GalNAc-α-(1→3)-diNAcBac-PP-undecaprenol α-1,4-N-acetyl-D-galactosaminyltransferase

Glossary: N,N'-diacetyl-D-bacillosamine = 2,4-diacetamido-2,4,6-trideoxy-D-glucopyranose

Other name(s): PglJ

Systematic name: UDP-N-acetyl-α-D-galactosamine:N-acetylgalactosaminyl-α-(1→3)-N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol 3-α-N-acetyl-D-galactosaminyltransferase

Comments: Isolated from Campylobacter jejuni. Part of a bacterial N-linked glycosylation pathway.

References:

2. Chen, M.M., Weerapana, E., Ciepichal, E., Stupak, J., Reid, C.W., Swiezewska, E. and Imperiali, B. Polyisoprenol specificity in the Campylobacter jejuni N-linked glycosylation pathway. Biochemistry 46 (2007) 14342-14348. [PMID: 18034500]

[EC 2.4.1.291 created 2012]

EC 2.4.1.292

Reaction: 3 UDP-N-acetyl-α-D-galactosamine + GalNAc-α-(1→4)-GalNAc-α-(1→3)-diNAcBac-PP-tritrans,heptacis-undecaprenol = 3 UDP + [GalNAc-α-(1→4)]₄-GalNAc-α-(1→3)-diNAcBac-PP-tritrans,heptacis-undecaprenol

Accepted name: GalNAc₅-diNAcBac-PP-undecaprenol β-1,3-glucosyltransferase

Glossary: diNAcBac = N,N'-diacetyl-D-bacillosamine = 2,4-diacetamido-2,4,6-trideoxy-D-glucopyranose

Other name(s): PglH

Systematic name: UDP-N-acetyl-α-D-galactosamine:GalNAc-α-(1→4)-GalNAc-α-(1→3)-diNAcBac-PP-tritrans,heptacis-undecaprenol 4-α-N-acetyl-D-galactosaminyltransferase

Comments: Isolated from Campylobacter jejuni. Part of a bacterial N-linked glycosylation pathway.

References:

2. Troutman, J.M. and Imperiali, B. Campylobacter jejuni PglH is a single active site processive polymerase that utilizes product inhibition to limit sequential glycosyl transfer reactions. Biochemistry 48 (2009) 2807-2816. [PMID: 19159314]

3. Borud, B., Viburiene, R., Hartley, M.D., Paulsen, B.S., Egge-Jacobsen, W., Imperiali, B. and Koomey, M. Genetic and molecular analyses reveal an evolutionary trajectory for glycan synthesis in a bacterial protein glycosylation system. Proc. Natl. Acad. Sci. USA 108 (2011) 9643-9648. [PMID: 21606362]

[EC 2.4.1.292 created 2012]

EC 2.4.1.293

Reaction: UDP-α-D-glucose + [GalNAc-α-(1→4)]₄-GalNAc-α-(1→3)-diNAcBac-diphospho-tritrans,heptacis-undecaprenol = UDP + [GalNAc-α-(1→4)]₂-[Glc-β-(1→3)]-[GalNAc-α-(1→4)]₂-GalNAc-α-(1→3)-diNAcBac-diphospho-tritrans,heptacis-undecaprenol

Accepted name: tRNA-guanine¹⁵ transglycosylase

Glossary: diNAcBac = N,N'-diacetyl-D-bacillosamine = 2,4-diacetamido-2,4,6-trideoxy-D-glucopyranose

Other name(s): PglI

Systematic name: UDP-α-D-glucose:[GalNAc-α-(1→4)]4-GalNAc-α-(1→3)-diNAcBac-diphospho-tritrans,heptacis-undecaprenol 3-β-D-glucosyltransferase

Comments: Isolated from the bacterium Campylobacter jejuni. Part of a bacterial N-linked glycosylation pathway.

References:

2. Kelly, J., Jarrell, H., Millar, L., Tessier, L., Fiori, L.M., Lau, P.C., Allan, B. and Szymanski, C.M. Biosynthesis of the N-linked glycan in Campylobacter jejuni and addition onto protein through block transfer. J. Bacteriol. 188 (2006) 2427-2434. [PMID: 16547029]

[EC 2.4.1.293 created 2012]

EC 2.4.2.48

Reaction: guanine¹⁵ in tRNA + 7-cyano-7-carbaguanine = 7-cyano-7-carbaguanine¹⁵ in tRNA + guanine

Glossary: 7-cyano-7-carbaguanine = preQ₀ = 7-cyano-7-deazaguanine
archaeosine = G* = 7-amidino-7-deazaguanosine

Other name(s): tRNA transglycosylase (ambiguous); transfer ribonucleate glycosyltransferase (ambiguous); tRNA guanine¹⁵ transglycosidase; TGT (ambiguous); transfer ribonucleic acid guanine¹⁵ transglycosylase

Systematic name: tRNA-guanine¹⁵:7-cyano-7-carbaguanine tRNA-D-ribosyltransferase

Comments: Archaeal tRNAs contain the modified nucleoside archaeosine at position 15. This archaeal enzyme catalyses the exchange of guanine at position 15 of tRNA with the base preQ₀, which is ultimately modified to form the nucleoside archaeosine (cf. EC 2.6.1.97) [1].

References:

1. Bai, Y., Fox, D.T., Lacy, J.A., Van Lanen, S.G. and Iwata-Reuyl, D. Hypermodification of tRNA in thermophilic archaea. Cloning, overexpression, and characterization of tRNA-guanine transglycosylase from Methanococcus jannaschii. J. Biol. Chem. 275 (2000) 28731-28738. [PMID: 10862614]

[EC 2.4.2.48 created 2012]

EC 2.4.99.18

Accepted name: dolichyl-diphosphooligosaccharide—protein glycotransferase

Reaction: dolichyl diphosphooligosaccharide + [protein]-L-asparagine = dolichyl diphosphate + a glycoprotein with the oligosaccharide chain attached by N-β-D-glycosyl linkage to a protein L-asparagine

Other name(s): dolichyldiphosphooligosaccharide-protein glycosyltransferase; asparagine N-glycosyltransferase; dolichyldiphosphooligosaccharide-protein oligosaccharyltransferase; dolichylpyrophosphodiacetylchitobiose-protein glycosyltransferase; oligomannosyltransferase; oligosaccharide transferase; dolichyldiphosphoryloligosaccharide-protein oligosaccharyltransferase; dolichyl-diphosphooligosaccharide:protein-L-asparagine oligopolysaccharidotransferase; STT3

Systematic name: dolichyl-diphosphooligosaccharide:protein-L-asparagine N-β-D-oligopolysaccharidotransferase

Comments: Occurs in eukaryotes that form a glycoprotein by the transfer of a glucosyl-mannosyl-glucosamine polysaccharide to the side-chain of an L-asparagine residue in the sequence -Asn-Xaa-Ser- or -Asn-Xaa-Thr- (Xaa not Pro) in nascent polypeptide chains. The basic oligosaccharide is the tetradecasaccharide Glc₃Man₉GlcNAc₂ (for diagram click here). However, smaller oligosaccharides derived from it and oligosaccharides with additional monosaccharide units attached may be involved. See ref [2] for a review of N-glycoproteins in eukaryotes. Man₃GlcNAc₂ seems to be common for all of the oligosaccharides involved with the terminal N-acetylglucosamine linked to the protein L-asparagine. Occurs on the cytosolic face of the endoplasmic reticulum. The dolichol involved normally has 14-21 isoprenoid units with two trans double-bonds at the ω end, and the rest of the double-bonds in cis form.

References:

1. Das, R.C. and Heath, E.C. Dolichyldiphosphoryloligosaccharide-protein oligosaccharyltransferase; solubilization, purification, and properties. Proc. Natl. Acad. Sci. USA 77 (1980) 3811-3815. [PMID: 6933437]

2. Song, W., Henquet, M.G., Mentink, R.A., van Dijk, A.J., Cordewener, J.H., Bosch, D., America, A.H. and van der Krol, A.R. N-glycoproteomics in plants: perspectives and challenges. J Proteomics 74 (2011) 1463-1474. [PMID: 21605711]

[EC 2.4.99.18 created 1984 as EC 2.4.1.119, transferred 2012 to EC 2.4.99.18]

EC 2.4.99.19

Accepted name: undecaprenyl-diphosphooligosaccharide—protein glycotransferase

Reaction: tritrans,heptacis-undecaprenyl diphosphooligosaccharide + [protein]-L-asparagine = tritrans,heptacis-undecaprenyl diphosphate + a glycoprotein with the oligosaccharide chain attached by N-β-D-glycosyl linkage to protein L-asparagine

Accepted name: squalene synthase

Other name(s): PglB

Systematic name: tritrans,heptacis-undecaprenyl-diphosphooligosaccharide:protein-L-asparagine N-β-D-oligosaccharidotransferase

Comments: A bacterial enzyme that has been isolated from Campylobacter jejuni [1] and Campylobacter lari [2]. It forms a glycoprotein by the transfer of a glucosyl-N-acetylgalactosaminyl-N,N'-diacetylbacillosamine (GalNAc₂(Glc)GalNAc₃diNAcBac) polysaccharide and related oligosaccharides to the side-chain of an L-asparagine residue in the sequence -Asp/Glu-Xaa-Asn-Xaa'-Ser/Thr- (Xaa and Xaa' not Pro) in nascent polypeptide chains. Requires Mn²⁺ or Mg²⁺. Occurs on the external face of the plasma membrane. The polyprenol involved is normally tritrans,heptacis-undecaprenol but a decaprenol is used by some species.

References:

1. Maita, N., Nyirenda, J., Igura, M., Kamishikiryo, J. and Kohda, D. Comparative structural biology of eubacterial and archaeal oligosaccharyltransferases. J. Biol. Chem. 285 (2010) 4941-4950. [PMID: 20007322]

2. Lizak, C., Gerber, S., Numao, S., Aebi, M. and Locher, K.P. X-ray structure of a bacterial oligosaccharyltransferase. Nature 474 (2011) 350-355. [PMID: 21677752]

[EC 2.4.99.19 created 2012]

*EC 2.5.1.21

Reaction: 2 (2E,6E)-farnesyl diphosphate + NAD(P)H + H⁺ = squalene + 2 diphosphate + NAD(P)⁺ (overall reaction)
(1a) 2 (2E,6E)-farnesyl diphosphate = diphosphate + presqualene diphosphate
(1b) presqualene diphosphate + NAD(P)H + H⁺ = squalene + diphosphate + NAD(P)⁺

Accepted name: 15-cis-phytoene synthase

Other name(s): farnesyltransferase; presqualene-diphosphate synthase; presqualene synthase; squalene synthetase; farnesyl-diphosphate farnesyltransferase; SQS

Systematic name: (2E,6E)-farnesyl-diphosphate:(2E,6E)-farnesyl-diphosphate farnesyltransferase

Comments: This microsomal enzyme catalyses the first committed step in the biosynthesis of sterols. The enzyme from yeast requires either Mg²⁺ or Mn²⁺ for activity. In the absence of NAD(P)H, presqualene diphosphate (PSPP) is accumulated. When NAD(P)H is present, presqualene diphosphate does not dissociate from the enzyme during the synthesis of squalene from farnesyl diphosphate (FPP) [8]. High concentrations of FPP inhibit the production of squalene but not of PSPP [8].

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9077-14-9

References:

1. Kuswick-Rabiega, G. and Rilling, H.C. Squalene synthetase. Solubilization and partial purification of squalene synthetase, copurification of presqualene pyrophosphate and squalene synthetase activities. J. Biol. Chem. 262 (1987) 1505-1509. [PMID: 3805037]

2. Ericsson, J., Appelkvist, E.L., Thelin, A., Chojnacki, T. and Dallner, G. Isoprenoid biosynthesis in rat liver peroxisomes. Characterization of cis-prenyltransferase and squalene synthetase. J. Biol. Chem. 267 (1992) 18708-18714. [PMID: 1527001]

3. Tansey, T.R. and Shechter, I. Structure and regulation of mammalian squalene synthase. Biochim. Biophys. Acta 1529 (2000) 49-62. [PMID: 11111077]

4. LoGrasso, P.V., Soltis, D.A. and Boettcher, B.R. Overexpression, purification, and kinetic characterization of a carboxyl-terminal-truncated yeast squalene synthetase. Arch. Biochem. Biophys. 307 (1993) 193-199. [PMID: 8239656]

5. Shechter, I., Klinger, E., Rucker, M.L., Engstrom, R.G., Spirito, J.A., Islam, M.A., Boettcher, B.R. and Weinstein, D.B. Solubilization, purification, and characterization of a truncated form of rat hepatic squalene synthetase. J. Biol. Chem. 267 (1992) 8628-8635. [PMID: 1569107]

6. Agnew, W.S. and Popják, G. Squalene synthetase. Stoichiometry and kinetics of presqualene pyrophosphate and squalene synthesis by yeast microsomes. J. Biol. Chem. 253 (1978) 4566-4573. [PMID: 26684]

7. Pandit, J., Danley, D.E., Schulte, G.K., Mazzalupo, S., Pauly, T.A., Hayward, C.M., Hamanaka, E.S., Thompson, J.F. and Harwood, H.J., Jr. Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis. J. Biol. Chem. 275 (2000) 30610-30617. [PMID: 10896663]

8. Radisky, E.S. and Poulter, C.D. Squalene synthase: steady-state, pre-steady-state, and isotope-trapping studies. Biochemistry 39 (2000) 1748-1760. [PMID: 10677224]

[EC 2.5.1.21 created 1976, modified 2005, modified 2012]

*EC 2.5.1.32

Reaction: 2 geranylgeranyl diphosphate = 15-cis-phytoene + 2 diphosphate (overall reaction)
(1a) 2 geranylgeranyl diphosphate = diphosphate + prephytoene diphosphate
(1b) prephytoene diphosphate = 15-cis-phytoene + diphosphate

Accepted name: all-trans-phytoene synthase

Other name(s): prephytoene-diphosphate synthase (ambiguous); phytoene synthetase (ambiguous); PSase (ambiguous); geranylgeranyl-diphosphate geranylgeranyltransferase (ambiguous)

Systematic name: geranylgeranyl-diphosphate:geranylgeranyl-diphosphate geranylgeranyltransferase (15-cis-phytoene forming)

Comments: Requires Mn²⁺ for activity. The enzyme produces 15-cis-phytoene. cf. EC 2.5.1.99, 15-trans-phytoene synthase.

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 50936-61-3

References:

1. Gregonis, D.E. and Rilling, H.C. The stereochemistry of trans-phytoene synthesis. Some observations on lycopersene as a carotene precursor and a mechanism for the synthesis of cis- and trans-phytoene. Biochemistry 13 (1974) 1538-1542. [PMID: 4819767]

2. Misawa, N., Truesdale, M.R., Sandmann, G., Fraser, P.D., Bird, C., Schuch, W. and Bramley, P.M. Expression of a tomato cDNA coding for phytoene synthase in Escherichia coli, phytoene formation in vivo and in vitro, and functional analysis of the various truncated gene products. J. Biochem. (Tokyo) 116 (1994) 980-985. [PMID: 7896759]

[EC 2.5.1.32 created 1984, modified 2005, modified 2012]

EC 2.5.1.99

Reaction: 2 geranylgeranyl diphosphate = all-trans-phytoene + 2 diphosphate (overall reaction)
(1a) 2 geranylgeranyl diphosphate = diphosphate + prephytoene diphosphate
(1b) prephytoene diphosphate = all-trans-phytoene + diphosphate

Accepted name: fumigaclavine A dimethylallyltransferase

Other name(s): prephytoene-diphosphate synthase (ambiguous); phytoene synthetase (ambiguous); PSase (ambiguous); geranylgeranyl-diphosphate geranylgeranyltransferase (ambiguous); 15-trans-phytoene synthase

Systematic name: geranylgeranyl-diphosphate:geranylgeranyl-diphosphate geranylgeranyltransferase (all-trans-phytoene forming)

Comments: Requires Mn²⁺ for activity. The enzyme from the bacterium Pantoea agglomerans (previously known as Erwinia herbicola) produces the all-trans isomer of phytoene. cf. EC 2.5.1.32, 15-cis-phytoene synthase.

References:

2. Iwata-Reuyl, D., Math, S.K., Desai, S.B. and Poulter, C.D. Bacterial phytoene synthase: molecular cloning, expression, and characterization of Erwinia herbicola phytoene synthase. Biochemistry 42 (2003) 3359-3365. [PMID: 12641468]

[EC 2.5.1.99 created 2012]

EC 2.5.1.100

Reaction: fumigaclavine A + dimethylallyl diphosphate = fumigaclavine C + diphosphate

Glossary: fumigaclavine A = 6,8β-dimethylergolin-9β-yl acetate
fumigaclavine C = 2-(2-methylbut-3-en-2-yl)-6,8β-dimethylergolin-9β-yl acetate

Other name(s): FgaPT1

Systematic name: dimethylallyl-diphosphate:fumigaclavine A dimethylallyltransferase

Comments: Fumigaclavine C is an ergot alkaloid produced by some fungi of the Trichocomaceae family. Activity does not require any metal ions.

1. Unsöld, I.A. and Li, S.M. Reverse prenyltransferase in the biosynthesis of fumigaclavine C in Aspergillus fumigatus: gene expression, purification, and characterization of fumigaclavine C synthase FGAPT1. ChemBioChem. 7 (2006) 158-164. [PMID: 16397874]

[EC 2.5.1.100 created 2012]

EC 2.5.1.101

Accepted name: N,N'-diacetyllegionaminate synthase

Reaction: 2,4-diacetamido-2,4,6-trideoxy-α-D-mannopyranose + phosphenolpyruvate + H₂O = N,N'-diacetyllegionaminate + phosphate

For diagram of reaction click here and mechanism click here.

Glossary: legionaminate = 5,7-diamino-3,5,7,9-tetradeoxy-D-glycero-D-galacto-non-2-ulosonate

Other name(s): neuB (gene name); legI (gene name)

Systematic name: phosphenolpyruvate:2,4-diacetamido-2,4,6-trideoxy-α-D-mannopyranose 1-(2-carboxy-2-oxoethyl)transferase

Comments: Requires a divalent metal such as Mn²⁺. Isolated from the bacteria Legionella pneumophila and Campylobacter jejuni, where it is involved in the biosynthesis of legionaminic acid, a virulence-associated, cell surface sialic acid-like derivative.

References:

1. Glaze, P.A., Watson, D.C., Young, N.M. and Tanner, M.E. Biosynthesis of CMP-N,N'-diacetyllegionaminic acid from UDP-N,N'-diacetylbacillosamine in Legionella pneumophila. Biochemistry 47 (2008) 3272-3282. [PMID: 18275154]

2. Schoenhofen, I.C., Vinogradov, E., Whitfield, D.M., Brisson, J.R. and Logan, S.M. The CMP-legionaminic acid pathway in Campylobacter: biosynthesis involving novel GDP-linked precursors. Glycobiology 19 (2009) 715-725. [PMID: 19282391]

[EC 2.5.1.101 created 2012]

EC 2.5.1.102

Accepted name: geranyl-pyrophosphate—olivetolic acid geranyltransferase

Reaction: geranyl diphosphate + 2,4-dihydroxy-6-pentylbenzoate = diphosphate + cannabigerolate

Accepted name: presqualene diphosphate synthase

Glossary: 2,4-dihydroxy-6-pentylbenzoate = olivetolate
cannabigerolate = CBGA = 3-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate
cannabinerolate = 3-[(2Z)-3,7-dimethylocta-2,6-dien-1-yl]-2,4-dihydroxy-6-pentylbenzoate

Other name(s): GOT (ambiguous)

Systematic name: geranyl-diphosphate:olivetolate geranyltransferase

Comments: Part of the cannabinoids biosynthetic pathway of the plant Cannabis sativa. The enzyme can also use neryl diphosphate as substrate, forming cannabinerolate.

References:

1. Fellermeier, M. and Zenk, M.H. Prenylation of olivetolate by a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEBS Lett 427 (1998) 283-285. [PMID: 9607329]

[EC 2.5.1.102 created 2012]

EC 2.5.1.103

Reaction: 2 (2E,6E)-farnesyl diphosphate = presqualene diphosphate + diphosphate

Accepted name: 4-aminobutyrate—2-oxoglutarate transaminase

Other name(s): SSL-1 (gene name)

Systematic name: (2E,6E)-farnesyl-diphosphate:(2E,6E)-farnesyl-diphosphate farnesyltransferase (presqualene diphosphate forming)

Comments: Isolated from the green alga Botryococcus braunii BOT22. Unlike EC 2.5.1.21, squalene synthase, where squalene is formed in one step from farnesyl diphosphate, in this alga the intermediate presqualene diphosphate is generated and released by this enzyme. This compound is then converted into either squalene (by EC 1.3.1.96, Botryococcus squalene synthase) or botryococcene (EC 1.3.1.97, botryococcene synthase).

References:

[EC 2.5.1.103 created 2012]

*EC 2.6.1.19

Reaction: 4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate

Accepted name: 4-aminobutyrate—pyruvate transaminase

Glossary: 4-aminobutanoate = γ-aminobutyrate = GABA

Other name(s): β-alanine-oxoglutarate transaminase; aminobutyrate aminotransferase (ambiguous); β-alanine aminotransferase; β-alanine-oxoglutarate aminotransferase; γ-aminobutyrate aminotransaminase (ambiguous); γ-aminobutyrate transaminase (ambiguous); γ-aminobutyrate-α-ketoglutarate aminotransferase; γ-aminobutyrate-α-ketoglutarate transaminase; γ-aminobutyrate:α-oxoglutarate aminotransferase; γ-aminobutyric acid aminotransferase (ambiguous); γ-aminobutyric acid transaminase (ambiguous); γ-aminobutyric acid-α-ketoglutarate transaminase; γ-aminobutyric acid-α-ketoglutaric acid aminotransferase; γ-aminobutyric acid-2-oxoglutarate transaminase; γ-aminobutyric transaminase (ambiguous); 4-aminobutyrate aminotransferase (ambiguous); 4-aminobutyrate-2-ketoglutarate aminotransferase; 4-aminobutyrate-2-oxoglutarate aminotransferase; 4-aminobutyrate-2-oxoglutarate transaminase; 4-aminobutyric acid 2-ketoglutaric acid aminotransferase; 4-aminobutyric acid aminotransferase (ambiguous); aminobutyrate transaminase (ambiguous); GABA aminotransferase (ambiguous); GABA transaminase (ambiguous); GABA transferase; GABA-α-ketoglutarate aminotransferase; GABA-α-ketoglutarate transaminase; GABA-α-ketoglutaric acid transaminase; GABA-α-oxoglutarate aminotransferase; GABA-2-oxoglutarate aminotransferase; GABA-2-oxoglutarate transaminase; GABA-oxoglutarate aminotransferase; GABA-oxoglutarate transaminase; glutamate-succinic semialdehyde transaminase; GabT

Systematic name: 4-aminobutanoate:2-oxoglutarate aminotransferase

Comments: Requires pyridoxal phosphate. Some preparations also act on β-alanine, 5-aminopentanoate and (R,S)-3-amino-2-methylpropanoate.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, PDB, CAS registry number: 9037-67-6

References:

1. Scott, E.M. and Jakoby, W.B. Soluble γ-aminobutyric-glutamic transaminase from Pseudomonas fluorescens. J. Biol. Chem. 234 (1959) 932-936. [PMID: 13654294]

2. Aurich, H. Über die β-Alanin-α-Ketoglutarat-Transaminase aus Neurospora crassa. Hoppe-Seyler's Z. Physiol. Chem. 326 (1961) 25-33. [PMID: 13863304]

3. Schausboe, A., Wu, J.-Y. and Roberts, E. Purification and characterization of the 4-aminobutyrate-2-ketoglutarate transaminase from mouse brain. Biochemistry 12 (1973) 2868-2873. [PMID: 4719123]

4. Bartsch, K., von Johnn-Marteville, A. and Schulz, A. Molecular analysis of two genes of the Escherichia coli gab cluster: nucleotide sequence of the glutamate:succinic semialdehyde transaminase gene (gabT) and characterization of the succinic semialdehyde dehydrogenase gene (gabD). J. Bacteriol. 172 (1990) 7035-7042. [PMID: 2254272]

[EC 2.6.1.19 created 1965, modified 1982, modified 2012]

EC 2.6.1.96

Reaction: (1) 4-aminobutanoate + pyruvate = succinate semialdehyde + L-alanine
(2) 4-aminobutanoate + glyoxylate = succinate semialdehyde + glycine

Other name(s): aminobutyrate aminotransferase (ambiguous); γ-aminobutyrate aminotransaminase (ambiguous); γ-aminobutyrate transaminase (ambiguous); γ-aminobutyric acid aminotransferase (ambiguous); γ-aminobutyric acid pyruvate transaminase; γ-aminobutyric acid transaminase (ambiguous); γ-aminobutyric transaminase (ambiguous); 4-aminobutyrate aminotransferase (ambiguous); 4-aminobutyric acid aminotransferase (ambiguous); aminobutyrate transaminase (ambiguous); GABA aminotransferase (ambiguous); GABA transaminase (ambiguous); GABA transferase; POP2 (gene name)

Systematic name: 4-aminobutanoate:pyruvate aminotransferase

Comments: Requires pyridoxal 5'-phosphate. The enzyme is found in plants that do not have the 2-oxoglutarate dependent enzyme (cf. EC 2.6.1.19). The reaction with pyruvate is reversible while the reaction with glyoxylate only takes place in the forward direction.

References:

1. Van Cauwenberghe, O.R. and Shelp, B.J. Biochemical characterization of partially purified gaba:pyruvate transaminase from Nicotiana tabacum. Phytochemistry 52 (1999) 575-581.

2. Palanivelu, R., Brass, L., Edlund, A.F. and Preuss, D. Pollen tube growth and guidance is regulated by POP2, an Arabidopsis gene that controls GABA levels. Cell 114 (2003) 47-59. [PMID: 12859897]

3. Clark, S.M., Di Leo, R., Dhanoa, P.K., Van Cauwenberghe, O.R., Mullen, R.T. and Shelp, B.J. Biochemical characterization, mitochondrial localization, expression, and potential functions for an Arabidopsis γ-aminobutyrate transaminase that utilizes both pyruvate and glyoxylate. J. Exp. Bot. 60 (2009) 1743-1757. [PMID: 19264755]

4. Clark, S.M., Di Leo, R., Van Cauwenberghe, O.R., Mullen, R.T. and Shelp, B.J. Subcellular localization and expression of multiple tomato γ-aminobutyrate transaminases that utilize both pyruvate and glyoxylate. J. Exp. Bot. 60 (2009) 3255-3267. [PMID: 19470656]

[EC 2.6.1.96 created 2012]

EC 2.6.1.97

Accepted name: archaeosine synthase

Reaction: L-glutamine + 7-cyano-7-carbaguanine¹⁵ in tRNA + H₂O = L-glutamate + archaeine¹⁵ in tRNA

Glossary: 7-cyano-7-carbaguanine = preQ₀ = 7-cyano-7-deazaguanine
archaeine = 7-deaza-7-carbamidoylguanine = base G*
archaeosine = G*

Other name(s): ArcS; TgtA2; MJ1022 (gene name); glutamine:preQ₀-tRNA amidinotransferase (incorrect)

Systematic name: L-glutamine:7-cyano-7-carbaguanine aminotransferase

Comments: In Euryarchaeota the reaction is catalysed by ArcS [1,2]. In Crenarchaeota, which do not have an ArcS homologue, the reaction is catalysed either by a homologue of EC 6.3.4.20, 7-cyano-7-deazaguanine synthase that includes a glutaminase domain (cf. EC 3.5.1.2), or by a homologue of EC 1.7.1.13, preQ₁ synthase [2]. The enzyme from the Euryarchaeon Methanocaldococcus jannaschii can also use arginine and ammonium as amino donors.

References:

1. Phillips, G., Chikwana, V.M., Maxwell, A., El-Yacoubi, B., Swairjo, M.A., Iwata-Reuyl, D. and de Crecy-Lagard, V. Discovery and characterization of an amidinotransferase involved in the modification of archaeal tRNA. J. Biol. Chem. 285 (2010) 12706-12713. [PMID: 20129918]

2. Phillips, G., Swairjo, M.A., Gaston, K.W., Bailly, M., Limbach, P.A., Iwata-Reuyl, D. and de Crecy-Lagard, V. Diversity of archaeosine synthesis in crenarchaeota. ACS Chem. Biol. 7 (2012) 300-305. [PMID: 22032275]

[EC 2.6.1.97 created 2012]

EC 2.6.1.98

Accepted name: UDP-2-acetamido-2-deoxy-ribo-hexuluronate aminotransferase

Reaction: UDP-2-acetamido-3-amino-2,3-dideoxy-α-D-glucuronate + 2-oxoglutarate = UDP-2-acetamido-2-deoxy-D-ribo-hex-3-uluronate + L-glutamate

Accepted name: L-tryptophan—pyruvate aminotransferase

Other name(s): WbpE; WlbC

Systematic name: UDP-2-acetamido-3-amino-2,3-dideoxy-α-D-glucuronate:2-oxoglutarate aminotransferase

Comments: A pyridoxal 5'-phosphate protein. This enzyme participates in the biosynthetic pathway for UDP-α-D-ManNAc3NAcA (UDP-2,3-diacetamido-2,3-dideoxy-α-D-mannuronic acid), an important precursor of B-band lipopolysaccharide. The enzymes from Pseudomonas aeruginosa serotype O5 and Thermus thermophilus form a complex with the previous enzyme in the pathway, EC 1.1.1.335 (UDP-N-acetyl-2-amino-2-deoxyglucuronate oxidase).

References:

3. Larkin, A., Olivier, N.B. and Imperiali, B. Structural analysis of WbpE from Pseudomonas aeruginosa PAO1: a nucleotide sugar aminotransferase involved in O-antigen assembly. Biochemistry 49 (2010) 7227-7237. [PMID: 20604544]

[EC 2.6.1.98 created 2012]

EC 2.6.1.99

Reaction: L-tryptophan + pyruvate = indole-3-pyruvate + L-alanine

Accepted name: [pyruvate, phosphate dikinase]-phosphate phosphotransferase

Other name(s): TAA1 (gene name); vt2 (gene name)

Systematic name: L-tryptophan:pyruvate aminotransferase

Comments: This plant enzyme, along with EC 1.14.13.168, indole-3-pyruvate monooxygenase, is responsible for the biosynthesis of the plant hormone indole-3-acetate from L-tryptophan.

References:

1. Tao, Y., Ferrer, J.L., Ljung, K., Pojer, F., Hong, F., Long, J.A., Li, L., Moreno, J.E., Bowman, M.E., Ivans, L.J., Cheng, Y., Lim, J., Zhao, Y., Ballare, C.L., Sandberg, G., Noel, J.P. and Chory, J. Rapid synthesis of auxin via a new tryptophan-dependent pathway is required for shade avoidance in plants. Cell 133 (2008) 164-176. [PMID: 18394996]

2. Mashiguchi, K., Tanaka, K., Sakai, T., Sugawara, S., Kawaide, H., Natsume, M., Hanada, A., Yaeno, T., Shirasu, K., Yao, H., McSteen, P., Zhao, Y., Hayashi, K., Kamiya, Y. and Kasahara, H. The main auxin biosynthesis pathway in Arabidopsis. Proc. Natl. Acad. Sci. USA 108 (2011) 18512-18517. [PMID: 22025724]

3. Phillips, K.A., Skirpan, A.L., Liu, X., Christensen, A., Slewinski, T.L., Hudson, C., Barazesh, S., Cohen, J.D., Malcomber, S. and McSteen, P. vanishing tassel2 encodes a grass-specific tryptophan aminotransferase required for vegetative and reproductive development in maize. Plant Cell 23 (2011) 550-566. [PMID: 21335375]

4. Zhao, Y. Auxin biosynthesis: a simple two-step pathway converts tryptophan to indole-3-acetic acid in plants. Mol. Plant 5 (2012) 334-338. [PMID: 22155950]

[EC 2.6.1.99 created 2012]

EC 2.7.4.27

Reaction: [pyruvate, phosphate dikinase] phosphate + phosphate = [pyruvate, phosphate dikinase] + diphosphate

Other name(s): PPDK regulatory protein (ambiguous); pyruvate, phosphate dikinase regulatory protein (ambiguous); bifunctional dikinase regulatory protein (ambiguous); PDRP1 (gene name)

Systematic name: [pyruvate, phosphate dikinase] phosphate:phosphate phosphotransferase

Comments: The enzyme from the plants maize and Arabidopsis is bifunctional and also catalyses the phosphorylation of pyruvate, phosphate dikinase (EC 2.7.9.1), cf. EC 2.7.11.32, [pyruvate, phosphate dikinase] kinase [2-5].

References:

1. Burnell, J.N. and Hatch, M.D. Regulation of C₄ photosynthesis: identification of a catalytically important histidine residue and its role in the regulation of pyruvate,P_i dikinase. Arch. Biochem. Biophys. 231 (1984) 175-182. [PMID: 6326674]

2. Burnell, J.N. and Hatch, M.D. Regulation of C₄ photosynthesis: purification and properties of the protein catalyzing ADP-mediated inactivation and P_i-mediated activation of pyruvate,P_i dikinase. Arch. Biochem. Biophys. 237 (1985) 490-503. [PMID: 2983615]

3. Chastain, C.J., Botschner, M., Harrington, G.E., Thompson, B.J., Mills, S.E., Sarath, G. and Chollet, R. Further analysis of maize C₄ pyruvate,orthophosphate dikinase phosphorylation by its bifunctional regulatory protein using selective substitutions of the regulatory Thr-456 and catalytic His-458 residues. Arch. Biochem. Biophys. 375 (2000) 165-170. [PMID: 10683263]

4. Burnell, J.N. and Chastain, C.J. Cloning and expression of maize-leaf pyruvate, P_i dikinase regulatory protein gene. Biochem. Biophys. Res. Commun. 345 (2006) 675-680. [PMID: 16696949]

5. Chastain, C.J., Xu, W., Parsley, K., Sarath, G., Hibberd, J.M. and Chollet, R. The pyruvate, orthophosphate dikinase regulatory proteins of Arabidopsis possess a novel, unprecedented Ser/Thr protein kinase primary structure. Plant J. 53 (2008) 854-863. [PMID: 17996018]

[EC 2.7.4.27 created 2012]

EC 2.7.4.28

Accepted name: [pyruvate, water dikinase]-phosphate phosphotransferase

Reaction: [pyruvate, water dikinase] phosphate + phosphate = [pyruvate, water dikinase] + diphosphate

Other name(s): PSRP (ambiguous)

Systematic name: [pyruvate, water dikinase] phosphate:phosphate phosphotransferase

References:

1. Burnell, J.N. Cloning and characterization of Escherichia coli DUF299: a bifunctional ADP-dependent kinase^--P_i-dependent pyrophosphorylase from bacteria. BMC Biochem. 11 (2010) 1. [PMID: 20044937]

[EC 2.7.4.28 created 2012]

*EC 2.7.7.23

Accepted name: UDP-N-acetylglucosamine diphosphorylase

Reaction: UTP + N-acetyl-α-D-glucosamine 1-phosphate = diphosphate + UDP-N-acetyl-α-D-glucosamine

Accepted name: CMP-N,N'-diacetyllegionaminic acid synthase

Other name(s): UDP-N-acetylglucosamine pyrophosphorylase; uridine diphosphoacetylglucosamine pyrophosphorylase; UTP:2-acetamido-2-deoxy-α-D-glucose-1-phosphate uridylyltransferase; UDP-GlcNAc pyrophosphorylase; GlmU uridylyltransferase; Acetylglucosamine 1-phosphate uridylyltransferase; UDP-acetylglucosamine pyrophosphorylase; uridine diphosphate-N-acetylglucosamine pyrophosphorylase; uridine diphosphoacetylglucosamine phosphorylase; acetylglucosamine 1-phosphate uridylyltransferase

Systematic name: UTP:N-acetyl-α-D-glucosamine-1-phosphate uridylyltransferase

Comments: Part of the pathway for acetamido sugar biosynthesis in bacteria and archaea. The enzyme from several bacteria (e.g., Escherichia coli, Bacillus subtilis and Hemophilus influenzae) has been shown to be bifunctional and also to possess the activity of EC 2.3.1.157, glucosamine-1-phosphate N-acetyltransferase [3,4,6]. The enzyme from plants and animals is also active toward N-acetyl-α-D-galactosamine 1-phosphate (cf. EC 2.7.7.83, UDP-N-acetylgalactosamine diphosphorylase) [5,7], while the bacterial enzyme shows low activity toward that substrate [4].

Links to other databases: BRENDA, EXPASY, GTD, KEGG, PDB, CAS registry number: 9023-06-7

References:

1. Pattabiramin, T.N. and Bachhawat, B.K. Purification of uridine diphosphoacetylglucosamine pyrophosphorylase from sheep brain. Biochim. Biophys. Acta 50 (1961) 129-134. [PMID: 13733356]

2. Strominger, J.L. and Smith, M.S. Uridine diphosphoacetylglucosamine pyrophosphorylase. J. Biol. Chem. 234 (1959) 1822-1827. [PMID: 13672971]

3. Mengin-Lecreulx, D. and van Heijenoort, J. Copurification of glucosamine-1-phosphate acetyltransferase and N-acetylglucosamine-1-phosphate uridyltransferase activities of Escherichia coli: characterization of the glmU gene product as a bifunctional enzyme catalyzing two subsequent steps in the pathway for UDP-N-acetylglucosamine synthesis. J. Bacteriol. 176 (1994) 5788-5795. [PMID: 8083170]

4. Gehring, A.M., Lees, W.J., Mindiola, D.J., Walsh, C.T. and Brown, E.D. Acetyltransfer precedes uridylyltransfer in the formation of UDP-N-acetylglucosamine in separable active sites of the bifunctional GlmU protein of Escherichia coli. Biochemistry 35 (1996) 579-585. [PMID: 8555230]

5. Wang-Gillam, A., Pastuszak, I. and Elbein, A.D. A 17-amino acid insert changes UDP-N-acetylhexosamine pyrophosphorylase specificity from UDP-GalNAc to UDP-GlcNAc. J. Biol. Chem. 273 (1998) 27055-27057. [PMID: 9765219]

6. Olsen, L.R. and Roderick, S.L. Structure of the Escherichia coli GlmU pyrophosphorylase and acetyltransferase active sites. Biochemistry 40 (2001) 1913-1921. [PMID: 11329257]

7. Peneff, C., Ferrari, P., Charrier, V., Taburet, Y., Monnier, C., Zamboni, V., Winter, J., Harnois, M., Fassy, F. and Bourne, Y. Crystal structures of two human pyrophosphorylase isoforms in complexes with UDPGlc(Gal)NAc: role of the alternatively spliced insert in the enzyme oligomeric assembly and active site architecture. EMBO J. 20 (2001) 6191-6202. [PMID: 11707391]

[EC 2.7.7.23 created 1965, modified 2012]

EC 2.7.7.82

Reaction: CTP + N,N'-diacetyllegionaminate = CMP-N,N'-diacetyllegionaminate + diphosphate

Accepted name: UDP-N-acetylgalactosamine diphosphorylase

Glossary: legionaminate = 5,7-diamino-3,5,7,9-tetradeoxy-D-glycero-D-galacto-non-2-ulosonate

Other name(s): CMP-N,N'-diacetyllegionaminic acid synthetase; neuA (gene name); legF (gene name)

Systematic name: CTP:N,N'-diacetyllegionaminate cytidylyltransferase

Comments: Isolated from the bacteria Legionella pneumophila and Campylobacter jejuni. Involved in biosynthesis of legionaminic acid, a sialic acid-like derivative that is incorporated into virulence-associated cell surface glycoconjugates which may include lipopolysaccharide (LPS), capsular polysaccharide, pili and flagella.

References:

[EC 2.7.7.82 created 2012]

EC 2.7.7.83

Reaction: UTP + N-acetyl-α-D-galactosamine 1-phosphate = diphosphate + UDP-N-acetyl-α-D-galactosamine

Systematic name: UTP:N-acetyl-α-D-galactosamine-1-phosphate uridylyltransferase

Comments: The enzyme from plants and animals also has activity toward N-acetyl-α-D-glucosamine 1-phosphate (cf. EC 2.7.7.23, UDP-N-acetylglucosamine diphosphorylase) [1,2].

References:

1. Wang-Gillam, A., Pastuszak, I. and Elbein, A.D. A 17-amino acid insert changes UDP-N-acetylhexosamine pyrophosphorylase specificity from UDP-GalNAc to UDP-GlcNAc. J. Biol. Chem. 273 (1998) 27055-27057. [PMID: 9765219]

2. Peneff, C., Ferrari, P., Charrier, V., Taburet, Y., Monnier, C., Zamboni, V., Winter, J., Harnois, M., Fassy, F. and Bourne, Y. Crystal structures of two human pyrophosphorylase isoforms in complexes with UDPGlc(Gal)NAc: role of the alternatively spliced insert in the enzyme oligomeric assembly and active site architecture. EMBO J. 20 (2001) 6191-6202. [PMID: 11707391]

[EC 2.7.7.83 created 2012]

EC 2.7.8.36

Accepted name: undecaprenyl phosphate N,N'-diacetylbacillosamine 1-phosphate transferase

Reaction: UDP-N,N'-diacetylbacillosamine + tritrans,heptacis-undecaprenyl phosphate = UMP + N,N'-diacetyl-α-D-bacillosaminyl-diphospho-tritrans,heptacis-undecaprenol

Accepted name: α-D-ribose 1-methylphosphonate 5-triphosphate synthase

Glossary: UDP-N,N'-diacetylbacillosamine = UDP-2,4-diacetamido-2,4,6-trideoxy-α-D-glucopyranose

Other name(s): PglC

Systematic name: UDP-N,N'-diacetylbacillosamine:tritrans,heptacis-undecaprenyl-phosphate N,N'-diacetylbacillosamine transferase

Comments: Isolated from Campylobacter jejuni. Part of a bacterial N-linked glycosylation pathway.

References:

1. Glover, K.J., Weerapana, E., Chen, M.M. and Imperiali, B. Direct biochemical evidence for the utilization of UDP-bacillosamine by PglC, an essential glycosyl-1-phosphate transferase in the Campylobacter jejuni N-linked glycosylation pathway. Biochemistry 45 (2006) 5343-5350. [PMID: 16618123]

[EC 2.7.8.36 created 2012]

EC 2.7.8.37

Reaction: ATP + methylphosphonate = α-D-ribose 1-methylphosphonate 5-triphosphate + adenine

Accepted name: [pyruvate, phosphate dikinase] kinase

Systematic name: ATP:methylphosphonate 5-triphosphoribosyltransferase

Comments: Isolated from the bacterium Escherichia coli.

References:

1. Kamat, S.S., Williams, H.J. and Raushel, F.M. Intermediates in the transformation of phosphonates to phosphate by bacteria. Nature 480 (2011) 570-573. [PMID: 22089136]

[EC 2.7.8.37 created 2012]

EC 2.7.11.32

Reaction: ADP + [pyruvate, phosphate dikinase] = AMP + [pyruvate, phosphate dikinase] phosphate

Other name(s): PPDK regulatory protein (ambiguous); pyruvate; phosphate dikinase regulatory protein (ambiguous); bifunctional dikinase regulatory protein (ambiguous)

Systematic name: ADP:[pyruvate, phosphate dikinase] phosphotransferase

Comments: The enzyme from the plants Zea mays (maize) and Arabidopsis is bifunctional and catalyses both the phosphorylation and dephosphorylation of pyruvate, phosphate dikinase (EC 2.7.9.1), cf. EC 2.7.4.27, [pyruvate, phosphate dikinase]-phosphate phosphotransferase [2-5]. The enzyme is specific for a reaction intermediate form of EC 2.7.9.1, and phosphorylates an active site histidine [3-5].

References:

4. Burnell, J.N. and Chastain, C.J. Cloning and expression of maize-leaf pyruvate, P_i dikinase regulatory protein gene. Biochem. Biophys. Res. Commun. 345 (2006) 675-680. [PMID: 16696949]

[EC 2.7.11.32 created 2012]

EC 2.7.11.33

Accepted name: [pyruvate, water dikinase] kinase

Reaction: ADP + [pyruvate, water dikinase] = AMP + [pyruvate, water dikinase] phosphate

Other name(s): PSRP (ambiguous); PEPS kinase

Systematic name: ADP:[pyruvate, water dikinase] phosphotransferase

Comments: The enzyme from the bacterium Escherichia coli is bifunctional and catalyses both the phosphorylation and dephosphorylation of EC 2.7.9.2, pyruvate, water dikinase. cf. EC 2.7.4.28, ([pyruvate, water dikinase] phosphate) phosphotransferase [1]. The enzyme is specific for a reaction intermediate form of EC 2.7.9.2, where it phosphorylates an active site histidine [1]. It has no activity toward EC 2.7.9.1 pyruvate, phosphate dikinase (cf. EC 2.7.11.32, [pyruvate, phosphate dikinase] kinase).

References:

1. Burnell, J.N. Cloning and characterization of Escherichia coli DUF299: a bifunctional ADP-dependent kinase—P_i-dependent pyrophosphorylase from bacteria. BMC Biochem. 11 (2010) 1. [PMID: 20044937]

[EC 2.7.11.33 created 2012]

EC 3.2.1.182

Accepted name: 4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl glucoside β-D-glucosidase

Reaction: (1) (2R)-4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside + H₂O = 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one + D-glucose
(2) (2R)-4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside + H₂O = 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one + D-glucose

Glossary: DIMBOA glucoside = (2R)-4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside
DIBOA glucoside = (2R)-4-hydroxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside

Other name(s): DIMBOAGlc hydrolase; DIMBOA glucosidase

Systematic name: (2R)-4-hydroxy-7-methoxy-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl β-D-glucopyranoside β-D-glucosidase

Comments: The enzyme from Triticum aestivum (wheat) has a higher affinity for DIMBOA glucoside than DIBOA glucoside. With Secale cereale (rye) the preference is reversed.

1. Sue, M., Ishihara, A. and Iwamura, H. Purification and characterization of a hydroxamic acid glucoside β-glucosidase from wheat (Triticum aestivum L.) seedlings. Planta 210 (2000) 432-438. [PMID: 10750901]

2. Sue, M., Ishihara, A. and Iwamura, H. Purification and characterization of a β-glucosidase from rye (Secale cereale L.) seedlings. Plant Sci. 155 (2000) 67-74. [PMID: 10773341]

3. Czjzek, M., Cicek, M., Zamboni, V., Bevan, D.R., Henrissat, B. and Esen, A. The mechanism of substrate (aglycone) specificity in β-glucosidases is revealed by crystal structures of mutant maize β-glucosidase-DIMBOA, -DIMBOAGlc, and -dhurrin complexes. Proc. Natl. Acad. Sci. USA 97 (2000) 13555-13560. [PMID: 11106394]

4. Nikus, J., Esen, A. and Jonsson, L.M.V. Cloning of a plastidic rye (Secale cereale) β-glucosidase cDNA and its expression in Escherichia coli. Physiol. Plantarum 118 (2003) 337-348.

5. Sue, M., Yamazaki, K., Yajima, S., Nomura, T., Matsukawa, T., Iwamura, H. and Miyamoto, T. Molecular and structural characterization of hexameric β-D-glucosidases in wheat and rye. Plant Physiol. 141 (2006) 1237-1247. [PMID: 16751439]

6. Sue, M., Nakamura, C., Miyamoto, T. and Yajima, S. Active-site architecture of benzoxazinone-glucoside β-D-glucosidases in Triticeae. Plant Sci. 180 (2011) 268-275. [PMID: 21421370]

[EC 3.2.1.182 created 2012]

EC 3.2.1.183

Accepted name: UDP-N-acetylglucosamine 2-epimerase (hydrolysing)

Reaction: UDP-N-acetyl-α-D-glucosamine + H₂O = N-acetyl-D-mannosamine + UDP

For diagram of reaction click here and mechanism click here.

Other name(s): UDP-N-acetylglucosamine 2-epimerase (ambiguous); GNE (gene name); siaA (gene name); neuC (gene name)

Systematic name: UDP-N-acetyl-α-D-glucosamine hydrolase (2-epimerising)

Comments: The enzyme is found in mammalian liver, as well as in some pathogenic bacteria including Neisseria meningitidis and Staphylococcus aureus. It catalyses the first step of sialic acid (N-acetylneuraminic acid) biosynthesis. The initial product formed is the α anomer, which rapidly mutarotates to a mixture of anomers [2]. The mammalian enzyme is bifunctional and also catalyses EC 2.7.1.60, N-acetylmannosamine kinase. cf. EC 5.1.3.14, UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing).

References:

1. Stasche, R., Hinderlich, S., Weise, C., Effertz, K., Lucka, L., Moormann, P. and Reutter, W. A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver. Molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase. J. Biol. Chem. 272 (1997) 24319-24324. [PMID: 9305888]

2. Chou, W.K., Hinderlich, S., Reutter, W. and Tanner, M.E. Sialic acid biosynthesis: stereochemistry and mechanism of the reaction catalyzed by the mammalian UDP-N-acetylglucosamine 2-epimerase. J. Am. Chem. Soc. 125 (2003) 2455-2461. [PMID: 12603133]

3. Blume, A., Ghaderi, D., Liebich, V., Hinderlich, S., Donner, P., Reutter, W. and Lucka, L. UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, functionally expressed in and purified from Escherichia coli, yeast, and insect cells. Protein Expr. Purif. 35 (2004) 387-396. [PMID: 15135418]

4. Murkin, A.S., Chou, W.K., Wakarchuk, W.W. and Tanner, M.E. Identification and mechanism of a bacterial hydrolyzing UDP-N-acetylglucosamine 2-epimerase. Biochemistry 43 (2004) 14290-14298. [PMID: 15518580]

[EC 3.2.1.183 created 2012]

EC 3.2.1.184

Accepted name: UDP-N,N'-diacetylbacillosamine 2-epimerase (hydrolysing)

Reaction: UDP-N,N'-diacetylbacillosamine + H₂O = UDP + 2,4-diacetamido-2,4,6-trideoxy-D-mannopyranose

For diagram of reaction click here and mechanism click here.

Glossary: UDP-N,N'-diacetylbacillosamine = UDP-2,4-diacetamido-2,4,6-trideoxy-α-D-glucopyranose

Other name(s): UDP-Bac2Ac₄Ac 2-epimerase; NeuC

Systematic name: UDP-N,N'-diacetylbacillosamine hydrolase (2-epimerising)

Comments: Requires Mg²⁺. Involved in biosynthesis of legionaminic acid, a nonulosonate derivative that is incorporated by some bacteria into assorted virulence-associated cell surface glycoconjugates. The initial product formed by the enzyme from Legionella pneumophila, which incorporates legionaminic acid into the O-antigen moiety of its lipopolysaccharide, is 2,4-diacetamido-2,4,6-trideoxy-α-D-mannopyranose, which rapidly mutarotates to a mixture of anomers [1]. The enzyme from Campylobacter jejuni, which incorporates legionaminic acid into flagellin, prefers GDP-N,N'-diacetylbacillosamine [2].

References:

[EC 3.2.1.184 created 2012]

EC 3.5.1.111

Accepted name: 2-oxoglutaramate amidase

Reaction: 2-oxoglutaramate + H₂O = 2-oxoglutarate + ammonia

Glossary: 2-oxoglutaramate = 2-ketoglutaramate = 5-amino-2,5-dioxopentanoate

Other name(s): ω-amidase (ambiguous)

Systematic name: 5-amino-2,5-dioxopentanoate amidohydrolase

Comments: The enzyme, which is highly specific for its substrate, participates in the nicotine degradation pathway of several Gram-positive bacteria.

1. Cobzaru, C., Ganas, P., Mihasan, M., Schleberger, P. and Brandsch, R. Homologous gene clusters of nicotine catabolism, including a new ω-amidase for α-ketoglutaramate, in species of three genera of Gram-positive bacteria. Res. Microbiol. 162 (2011) 285-291. [PMID: 21288482]

[EC 3.5.1.111 created 2012]

EC 3.5.1.112

Accepted name: 2'-N-acetylparomamine deacetylase

Reaction: 2'-N-acetylparomamine + H₂O = paromamine + acetate

Glossary: paromamine = (1R)-O₄^-(2-amino-2-deoxy^--D-glucopyranosyl)-2-deoxy-streptamine

Other name(s): btrD (gene name); neoL (gene name); kanN (gene name)

Systematic name: 2'-N-acetylparomamine hydrolase (acetate-forming)

Comments: Involved in the biosynthetic pathways of several clinically important aminocyclitol antibiotics, including kanamycin, butirosin, neomycin and ribostamycin. The enzyme from the bacterium Streptomyces fradiae can also accept 2'''-acetyl-6'''-hydroxyneomycin C as substrate, cf. EC 3.5.1.113, 2'''-acetyl-6'''-hydroxyneomycin C deacetylase [2].

References:

1. Truman, A.W., Huang, F., Llewellyn, N.M. and Spencer, J.B. Characterization of the enzyme BtrD from Bacillus circulans and revision of its functional assignment in the biosynthesis of butirosin. Angew. Chem. Int. Ed. Engl. 46 (2007) 1462-1464. [PMID: 17226887]

2. Yokoyama, K., Yamamoto, Y., Kudo, F. and Eguchi, T. Involvement of two distinct N-acetylglucosaminyltransferases and a dual-function deacetylase in neomycin biosynthesis. ChemBioChem. 9 (2008) 865-869. [PMID: 18311744]

[EC 3.5.1.112 created 2012]

EC 3.5.1.113

Accepted name: 2'''-acetyl-6'''-hydroxyneomycin C deacetylase

Reaction: 2'''-acetyl-6'''-deamino-6'''-hydroxyneomycin C + H₂O = 6'''-deamino-6'''-hydroxyneomycin C + acetate

Other name(s): neoL (gene name)

Systematic name: 2'''-acetyl-6'''-hydroxyneomycin C hydrolase (acetate-forming)

Comments: Involved in the biosynthetic pathway of aminoglycoside antibiotics of the neomycin family. The enzyme from the bacterium Streptomyces fradiae also catalyses EC 3.5.1.112, 2'-N-acetylparomamine deacetylase.

References:

1. Yokoyama, K., Yamamoto, Y., Kudo, F. and Eguchi, T. Involvement of two distinct N-acetylglucosaminyltransferases and a dual-function deacetylase in neomycin biosynthesis. ChemBioChem. 9 (2008) 865-869. [PMID: 18311744]

[EC 3.5.1.113 created 2012]

EC 3.6.1.63

Accepted name: α-D-ribose 1-methylphosphonate 5-triphosphate diphosphatase

Reaction: α-D-ribose 1-methylphosphonate 5-triphosphate + H₂O = α-D-ribose 1-methylphosphonate 5-phosphate + diphosphate

Accepted name: 3-fumarylpyruvate hydrolase

Other name(s): phnM (gene name)

Systematic name: α-D-ribose-1-methylphosphonate-5-triphosphate diphosphohydrolase

Comments: Isolated from the bacterium Escherichia coli.

References:

1. Kamat, S.S., Williams, H.J. and Raushel, F.M. Intermediates in the transformation of phosphonates to phosphate by bacteria. Nature 480 (2011) 570-573. [PMID: 22089136]

[EC 3.6.1.63 created 2012]

EC 3.7.1.20

Reaction: 3-fumarylpyruvate + H₂O = fumarate + pyruvate

Other name(s): nagK (gene name); naaD (gene name)

Systematic name: 3-fumarylpyruvate hydrolyase

Comments: The enzyme is involved in bacterial degradation of 5-substituted salicylates, including gentisate (5-hydroxysalicylate), 5-nitrosalicylate and 5-halosalicylates.

1. Zhou, N.Y., Fuenmayor, S.L. and Williams, P.A. nag genes of Ralstonia (formerly Pseudomonas) sp. strain U2 encoding enzymes for gentisate catabolism. J. Bacteriol. 183 (2001) 700-708. [PMID: 11133965]

2. Qu, Y. and Spain, J.C. Molecular and biochemical characterization of the 5-nitroanthranilic acid degradation pathway in Bradyrhizobium sp. strain JS329. J. Bacteriol. 193 (2011) 3057-3063. [PMID: 21498645]

[EC 3.7.1.20 created 2012]

[EC 4.2.1.52 Transferred entry: dihydrodipicolinate synthase. Now EC 4.3.3.7, 4-hydroxy-2,3,4,5-tetrahydrodipicolinate synthase. (EC 4.2.1.52 created 1972, transferred 2012 to EC 4.3.3.7, deleted 2012)]

*EC 4.2.1.54

Accepted name: lactoyl-CoA dehydratase

Reaction: (R)-lactoyl-CoA = acryloyl-CoA + H₂O

Other name(s): lactoyl coenzyme A dehydratase; lactyl-coenzyme A dehydrase; lactyl CoA dehydratase; acrylyl coenzyme A hydratase; lactoyl-CoA hydro-lyase

Systematic name: (R)-lactoyl-CoA hydro-lyase (acryloyl-CoA-forming)

Comments: A bacterial enzyme that is involved in propanoate fermentation (also known as the acrylate pathway).

Links to other databases: BRENDA, EXPASY, KEGG, UM-BBD, CAS registry number: 9031-12-3

References:

1. Baldwin, R.L., Wood, W.A. and Emery, R.S. Lactate metabolism by Peptostreptococcus elsdenii: evidence for lactyl coenzyme a dehydrase. Biochim. Biophys. Acta 97 (1965) 202-213. [PMID: 14292829]

2. Schweiger, G. and Buckel, W. On the dehydration of (R)-lactate in the fermentation of alanine to propionate by Clostridium propionicum. FEBS Lett 171 (1984) 79-84. [PMID: 6586495]

3. Kuchta, R.D. and Abeles, R.H. Lactate reduction in Clostridium propionicum. Purification and properties of lactyl-CoA dehydratase. J. Biol. Chem. 260 (1985) 13181-13189. [PMID: 4055736]

4. Kuchta, R.D., Hanson, G.R., Holmquist, B. and Abeles, R.H. Fe-S centers in lactyl-CoA dehydratase. Biochemistry 25 (1986) 7301-7307. [PMID: 3026450]

5. Hofmeister, A.E. and Buckel, W. (R)-lactyl-CoA dehydratase from Clostridium propionicum. Stereochemistry of the dehydration of (R)-2-hydroxybutyryl-CoA to crotonyl-CoA. Eur. J. Biochem. 206 (1992) 547-552. [PMID: 1597194]

[EC 4.2.1.54 created 1972, modified 2012]

*EC 4.2.1.93

Accepted name: ATP-dependent NAD(P)H-hydrate dehydratase

Reaction: (1) ATP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = ADP + phosphate + NADH
(2) ATP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = ADP + phosphate + NADPH

Accepted name: UDP-N-acetylglucosamine 4,6-dehydratase (configuration-retaining)

Glossary: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = (S)-NADH-hydrate = (S)-NADHX
(6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = (S)-NADPH-hydrate = (S)-NADPHX

Other name(s): reduced nicotinamide adenine dinucleotide hydrate dehydratase; ATP-dependent H₄NAD(P)⁺OH dehydratase; (6S)-β-6-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase(ATP-hydrolysing); (6S)-6-β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ATP-hydrolysing; NADH-forming)

Systematic name: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ATP-hydrolysing; NADH-forming)

Comments: Acts equally well on hydrated NADH and hydrated NADPH. NAD(P)H spontaneously hydrates to both the (6S)- and (6R)- isomers, and these are interconverted by EC 5.1.99.6, NAD(P)H-hydrate epimerase, to a 60:40 ratio [4]. Hence EC 4.2.1.93 together with EC 5.1.99.6 can restore the mixture of hydrates into NAD(P)H [3,4]. The enzyme from eukaryotes has no activity with ADP, contrary to the enzyme from bacteria (cf. EC 4.2.1.136, ADP-dependent NAD(P)H-hydrate dehydratase) [4].

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 116669-08-0

References:

1. Meinhart, J.O., Chaykin, S. and Krebs, E.G. Enzymatic conversion of a reduced diphosphopyridine nucleotide derivative to reduced diphosphopyridine nucleotide. J. Biol. Chem. 220 (1956) 821-829. [PMID: 13331940]

2. Regueiro Varela, B., Amelunxen, R. and Grisolia, S. Synthesis and degradation of monohydroxytetrahydronicotinamide adenine dinucleotide phosphate. Physiol. Chem. Phys. 2 (1970) 445-454.

3. Acheson, S.A., Kirkman, H.N. and Wolfenden, R. Equilibrium of 5,6-hydration of NADH and mechanism of ATP-dependent dehydration. Biochemistry 27 (1988) 7371-7375. [PMID: 3061454]

4. Marbaix, A.Y., Noel, G., Detroux, A.M., Vertommen, D., Van Schaftingen, E. and Linster, C.L. Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair. J. Biol. Chem. 286 (2011) 41246-41252. [PMID: 21994945]

[EC 4.2.1.93 created 1992, modified 2012]

EC 4.2.1.135

Reaction: UDP-N-acetyl-α-D-glucosamine = UDP-2-acetamido-2,6-dideoxy-α-D-xylo-hex-4-ulose + H₂O

For diagram of reaction click here and mechanism click here.

Glossary: N,N'-diacetylbacillosamine = 2,4-diacetamido-2,4,6-trideoxy-α-D-glucopyranose

Other name(s): PglF

Systematic name: UDP-N-acetyl-α-D-glucosamine hydro-lyase (configuration-retaining; UDP-2-acetamido-2,6-dideoxy-α-D-xylo-hex-4-ulose-forming)

Comments: Contains NAD⁺ as a cofactor [2]. This is the first enzyme in the biosynthetic pathway of N,N'-diacetylbacillosamine [1], the first carbohydrate in the glycoprotein N-linked heptasaccharide in Campylobacter jejuni. This enzyme belongs to the short-chain dehydrogenase/reductase family of enzymes.

References:

1. Schoenhofen, I.C., McNally, D.J., Vinogradov, E., Whitfield, D., Young, N.M., Dick, S., Wakarchuk, W.W., Brisson, J.R. and Logan, S.M. Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways. J. Biol. Chem. 281 (2006) 723-732. [PMID: 16286454]

2. Olivier, N.B., Chen, M.M., Behr, J.R. and Imperiali, B. In vitro biosynthesis of UDP-N,N'-diacetylbacillosamine by enzymes of the Campylobacter jejuni general protein glycosylation system. Biochemistry 45 (2006) 13659-13669. [PMID: 17087520]

[EC 4.2.1.135 created 2012]

EC 4.2.1.136

Accepted name: ADP-dependent NAD(P)H-hydrate dehydratase

Reaction: (1) ADP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = AMP + phosphate + NADH
(2) ADP + (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = AMP + phosphate + NADPH

Other name(s): (6S)-β-6-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase(ADP-hydrolysing); (6S)-6-β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ADP-hydrolysing; NADH-forming)

Systematic name: (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine-dinucleotide hydro-lyase (ADP-hydrolysing; NADH-forming)

Comments: Acts equally well on hydrated NADH and hydrated NADPH. NAD(P)H spontaneously hydrates to both the (6S)- and (6R)- isomers. The enzyme from bacteria consists of two domains, one of which acts as an NAD(P)H-hydrate epimerase that interconverts the two isomers to a 60:40 ratio (cf. EC 5.1.99.6), while the other catalyses the dehydration. Hence the enzyme can restore the complete mixture of isomers into NAD(P)H. The enzyme has no activity with ATP, contrary to the enzyme from eukaryotes (cf. EC 4.2.1.93, ATP-dependent NAD(P)H-hydrate dehydratase).

References:

1. Marbaix, A.Y., Noel, G., Detroux, A.M., Vertommen, D., Van Schaftingen, E. and Linster, C.L. Extremely conserved ATP- or ADP-dependent enzymatic system for nicotinamide nucleotide repair. J. Biol. Chem. 286 (2011) 41246-41252. [PMID: 21994945]

[EC 4.2.1.136 created 2012]

EC 4.2.1.137

Accepted name: sporulenol synthase

Reaction: sporulenol = tetraprenyl-β-curcumene + H₂O

Accepted name: 5-phosphonooxy-L-lysine phospho-lyase

Glossary: sporulenol = (1R,2R,4aS,4bR,6aS,10aS,10bR,12aS)-2,4b,7,7,10a,12a-hexamethyl-1-[(3R)-3-(4-methylcyclohexa-1,4-dien-1-yl)butyl]octadecahydrochrysen-2-ol

Other name(s): sqhC (gene name)

Systematic name: tetraprenyl-β-curcumene—sporulenol cyclase

Comments: The reaction occurs in the reverse direction. Isolated from Bacillus subtilis. Similar sesquarterpenoids are present in a number of Bacillus species.

References:

1. Sato, T., Yoshida, S., Hoshino, H., Tanno, M., Nakajima, M. and Hoshino, T. Sesquarterpenes (C₃₅ terpenes) biosynthesized via the cyclization of a linear C₃₅ isoprenoid by a tetraprenyl-β-curcumene synthase and a tetraprenyl-β-curcumene cyclase: identification of a new terpene cyclase. J. Am. Chem. Soc. 133 (2011) 9734-9737. [PMID: 21627333]

[EC 4.2.1.137 created 2012]

EC 4.2.3.134

Reaction: (5R)-5-phosphonooxy-L-lysine + H₂O = (S)-2-amino-6-oxohexanoate + NH₃ + phosphate

Other name(s): 5-phosphohydroxy-L-lysine ammoniophospholyase; AGXT2L2 (gene name)

Systematic name: (5R)-5-phosphonooxy-L-lysine phosphate-lyase (deaminating; (S)-2-amino-6-oxohexanoate-forming)

Comments: A pyridoxal-phosphate protein. Has no activity with phosphoethanolamine (cf. EC 4.2.3.2, ethanolamine-phosphate phospho-lyase).

References:

1. Tsai, C.H. and Henderson, L.M. Degradation of O-phosphohydroxylysine by rat liver. Purification of the phospho-lyase. J. Biol. Chem. 249 (1974) 5784-5789. [PMID: 4412716]

2. Veiga-da-Cunha, M., Hadi, F., Balligand, T., Stroobant, V. and Van Schaftingen, E. Molecular identification of hydroxylysine kinase and of ammoniophospholyases acting on 5-phosphohydroxy-L-lysine and phosphoethanolamine. J. Biol. Chem. 287 (2012) 7246-7255. [PMID: 22241472]

[EC 4.2.3.134 created 2012]

EC 4.2.3.135

Accepted name: Δ⁶-protoilludene synthase

Reaction: (2E,6E)-farnesyl diphosphate = Δ⁶-protoilludene + diphosphate

Accepted name: α-isocomene synthase

Glossary: Δ⁶-protoilludene = (4aS,7aS,7bR)-3,6,6,7b-tetramethyl-2,4,4a,5,6,7,7a,7b-octahydro-1H-cyclobuta[1,2-e]indene

Other name(s): 6-protoilludene synthase

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, Δ⁶-protoilludene-forming)

Comments: Isolated from the fungus Armillaria gallica. Δ⁶-Protoilludene is the first step in the biosynthesis of the melleolides.

References:

1. Engels, B., Heinig, U., Grothe, T., Stadler, M. and Jennewein, S. Cloning and characterization of an Armillaria gallica cDNA encoding protoilludene synthase, which catalyzes the first committed step in the synthesis of antimicrobial melleolides. J. Biol. Chem. 286 (2011) 6871-6878. [PMID: 21148562]

[EC 4.2.3.135 created 2012]

EC 4.2.3.136

Reaction: (2E,6E)-farnesyl diphosphate = (–)-α-isocomene + diphosphate

Accepted name: (E)-2-epi-β-caryophyllene synthase

Glossary: (–)-α-isocomene = (1R,3aS,5aS,8aR)-1,3a,4,5a-tetramethyl-1,2,3,3a,5a,6,7,8-octahydrocyclopenta[c]pentalene

Other name(s): MrTPS2

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (–)-α-isocomene-forming)

Comments: Isolated from the roots of the plant Matricaria chamomilla var. recutita (chamomile). The enzyme also produced traces of five other sesquiterpenoids.

References:

1. Irmisch, S., Krause, S.T., Kunert, G., Gershenzon, J., Degenhardt, J. and Kollner, T.G. The organ-specific expression of terpene synthase genes contributes to the terpene hydrocarbon composition of chamomile essential oils. BMC Plant Biol. 12 (2012) 84. [PMID: 22682202]

[EC 4.2.3.136 created 2012]

EC 4.2.3.137

Reaction: (2E,6E)-farnesyl diphosphate = (E)-2-epi-β-caryophyllene + diphosphate

Other name(s): 2-epi-(E)-β-caryophyllene synthase; SmMTPSL26

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (E)-2-epi-β-caryophyllene-forming)

Comments: Isolated from the plant Selaginella moellendorfii. The enzyme also gives two other sesquiterpenoids.

1. Li, G., Kollner, T.G., Yin, Y., Jiang, Y., Chen, H., Xu, Y., Gershenzon, J., Pichersky, E. and Chen, F. Nonseed plant Selaginella moellendorfii has both seed plant and microbial types of terpene synthases. Proc. Natl. Acad. Sci. USA 109 (2012) 14711-14715. [PMID: 22908266]

[EC 4.2.3.137 created 2012]

EC 4.2.3.138

Accepted name: (+)-epi-α-bisabolol synthase

Reaction: (2E,6E)-farnesyl diphosphate + H₂O = (+)-epi-α-bisabolol + diphosphate

Accepted name: valerena-4,7(11)-diene synthase

Glossary: (+)-epi-α-bisabolol = (2S)-6-methyl-2-[(1R)-4-methylcyclohex-3-en-1-yl]hept-5-en-2-ol

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-epi-α-bisabolol-forming)

Comments: Isolated from the plant Phyla dulcis (Aztec sweet herb). (+)-epi-α-Bisabolol is the precursor of the sweetener hernandulcin.

References:

1. Attia, M., Kim, S.U. and Ro, D.K. Molecular cloning and characterization of (+)-epi-α-bisabolol synthase, catalyzing the first step in the biosynthesis of the natural sweetener, hernandulcin, in Lippia dulcis. Arch. Biochem. Biophys. 527 (2012) 37-44. [PMID: 22867794]

[EC 4.2.3.138 created 2012]

EC 4.2.3.139

Reaction: (2E,6E)-farnesyl diphosphate = valerena-4,7(11)-diene + diphosphate

Accepted name: cis-abienol synthase

Glossary: valerena-4,7(11)-diene = (4S,7R,7aR)-3,7-dimethyl-4-(2-methylprop-1-en-1-yl)-2,4,5,6,7,7a-hexahydro-1H-indene

Other name(s): VoTPS2

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, valerena-4,7(11)-diene-forming)

Comments: Isolated from the plant Valeriana officinalis (valerian).

References:

1. Pyle, B.W., Tran, H.T., Pickel, B., Haslam, T.M., Gao, Z., Macnevin, G., Vederas, J.C., Kim, S.U. and Ro, D.K. Enzymatic synthesis of valerena-4,7(11)-diene by a unique sesquiterpene synthase from the valerian plant (Valeriana officinalis). FEBS J. 279 (2012) 3136-3146. [PMID: 22776156]

[EC 4.2.3.139 created 2012]

EC 4.2.3.140

Reaction: (13E)-8α-hydroxylabd-13-en-15-yl diphosphate = cis-abienol + diphosphate

Accepted name: L-lysine cyclodeaminase

Glossary: cis-abienol = (12Z)-labda-12,14-dien-8α-ol
(13E)-8α-hydroxylabd-13-en-15-yl diphosphate = copal-8-ol diphosphate

Other name(s): Z-abienol synthase; CAS; ABS

Systematic name: (13E)-8α-hydroxylabd-13-en-15-yl-diphosphate-lyase (cis-abienol forming)

Comments: Isolated from the plants Abies balsamea (balsam fir) [1] and Nicotiana tabacum (tobacco) [2].

References:

1. Zerbe, P., Chiang, A., Yuen, M., Hamberger, B., Hamberger, B., Draper, J.A., Britton, R. and Bohlmann, J. Bifunctional cis-abienol synthase from Abies balsamea discovered by transcriptome sequencing and its implications for diterpenoid fragrance production. J. Biol. Chem. 287 (2012) 12121-12131. [PMID: 22337889]

2. Sallaud, C., Giacalone, C., Topfer, R., Goepfert, S., Bakaher, N., Rosti, S. and Tissier, A. Characterization of two genes for the biosynthesis of the labdane diterpene Z-abienol in tobacco (Nicotiana tabacum) glandular trichomes. Plant J. 72 (2012) 1-17. [PMID: 22672125]

[EC 4.2.3.140 created 2012]

EC 4.3.1.28

Reaction: L-lysine = L-pipecolate + NH₃

Other name(s): rapL (gene name); fkbL (gene name); tubZ (gene name); visC (gene name)

Systematic name: L-lysine ammonia-lyase (cyclizing; ammonia-forming)

Comments: Requires bound NAD⁺. The enzyme produces the non-proteinogenic amino acid L-pipecolate, which is incorporated into multiple secondary metabolite products, including rapamycin, tobulysin, virginiamycin and pristinamycin.

1. Khaw, L.E., Bohm, G.A., Metcalfe, S., Staunton, J. and Leadlay, P.F. Mutational biosynthesis of novel rapamycins by a strain of Streptomyces hygroscopicus NRRL 5491 disrupted in rapL, encoding a putative lysine cyclodeaminase. J. Bacteriol. 180 (1998) 809-814. [PMID: 9473033]

2. Gatto, G.J., Jr., Boyne, M.T., 2nd, Kelleher, N.L. and Walsh, C.T. Biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase encoded in the rapamycin gene cluster. J. Am. Chem. Soc. 128 (2006) 3838-3847. [PMID: 16536560]

3. Tsotsou, G.E. and Barbirato, F. Biochemical characterisation of recombinant Streptomyces pristinaespiralis L-lysine cyclodeaminase. Biochimie 89 (2007) 591-604. [PMID: 17291665]

[EC 4.3.1.28 created 2012]

EC 4.3.3.7

Accepted name: 4-hydroxy-tetrahydrodipicolinate synthase

Reaction: pyruvate + L-aspartate-4-semialdehyde = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate + H₂O

Accepted name: olivetolic acid cyclase

Glossary: (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate = (2S,4S)-4-hydroxy-2,3,4,5-tetrahydropyridine-2,6-dicarboxylate

Other name(s): dihydrodipicolinate synthase (incorrect); dihydropicolinate synthetase (incorrect); dihydrodipicolinic acid synthase (incorrect); L-aspartate-4-semialdehyde hydro-lyase (adding pyruvate and cyclizing); dapA (gene name).

Systematic name: L-aspartate-4-semialdehyde hydro-lyase [adding pyruvate and cyclizing; (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinate-forming]

Comments: Studies of the enzyme from the bacterium Escherichia coli have shown that the reaction can be divided into three consecutive steps: Schiff base formation between pyruvate and an active-site lysine, the addition of L-aspartate-semialdehyde, and finally transimination leading to cyclization with simultaneous dissociation of the product.

References:

1. Yugari, Y. and Gilvarg, C. The condensation step in diaminopimelate synthesis. J. Biol. Chem. 240 (1965) 4710-4716. [PMID: 5321309]

2. Blickling, S., Renner, C., Laber, B., Pohlenz, H.D., Holak, T.A. and Huber, R. Reaction mechanism of Escherichia coli dihydrodipicolinate synthase investigated by X-ray crystallography and NMR spectroscopy. Biochemistry 36 (1997) 24-33. [PMID: 8993314]

3. Devenish, S.R., Blunt, J.W. and Gerrard, J.A. NMR studies uncover alternate substrates for dihydrodipicolinate synthase and suggest that dihydrodipicolinate reductase is also a dehydratase. J Med Chem 53 (2010) 4808-4812. [PMID: 20503968]

4. Soares da Costa, T.P., Muscroft-Taylor, A.C., Dobson, R.C., Devenish, S.R., Jameson, G.B. and Gerrard, J.A. How essential is the 'essential' active-site lysine in dihydrodipicolinate synthase. Biochimie 92 (2010) 837-845. [PMID: 20353808]

[EC 4.3.3.7 created 1972 as EC 4.2.1.52, transferred 2012 to EC 4.3.3.7]

EC 4.4.1.26

Reaction: 3,5,7-trioxododecanoyl-CoA = CoA + 2,4-dihydroxy-6-pentylbenzoate

Accepted name: UDP-N-acetylglucosamine 2-epimerase (non-hydrolysing)

Glossary: 2,4-dihydroxy-6-pentylbenzoate = olivetolate

Other name(s): OAC

Systematic name: 3,5,7-trioxododecanoyl-CoA CoA-lyase (olivetolate-forming)

Comments: Part of the cannabinoids biosynthetic pathway in the plant Cannabis sativa.

References:

1. Gagne, S.J., Stout, J.M., Liu, E., Boubakir, Z., Clark, S.M. and Page, J.E. Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc. Natl. Acad. Sci. USA 109 (2012) 12811-12816. [PMID: 22802619]

[EC 4.4.1.26 created 2012]

*EC 5.1.3.14

Reaction: UDP-N-acetyl-α-D-glucosamine = UDP-N-acetyl-α-D-mannosamine

Accepted name: dTDP-L-rhamnose 4-epimerase

Other name(s): UDP-N-acetylglucosamine 2'-epimerase (ambiguous); uridine diphosphoacetylglucosamine 2'-epimerase (ambiguous); uridine diphospho-N-acetylglucosamine 2'-epimerase (ambiguous); uridine diphosphate-N-acetylglucosamine-2'-epimerase (ambiguous); rffE (gene name); mnaA (gene name); UDP-N-acetyl-D-glucosamine 2-epimerase

Systematic name: UDP-N-acetyl-α-D-glucosamine 2-epimerase

Comments: This bacterial enzyme catalyses the reversible interconversion of UDP-GlcNAc and UDP-ManNAc. The latter is used in a variety of bacterial polysaccharide biosyntheses. cf. EC 3.2.1.183, UDP-N-acetylglucosamine 2-epimerase (hydrolysing).

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 9037-71-2

References:

1. Kawamura, T., Kimura, M., Yamamori, S. and Ito, E. Enzymatic formation of uridine diphosphate N-acetyl-D-mannosamine. J. Biol. Chem. 253 (1978) 3595-3601. [PMID: 418068]

2. Meier-Dieter, U., Starman, R., Barr, K., Mayer, H. and Rick, P.D. Biosynthesis of enterobacterial common antigen in Escherichia coli. Biochemical characterization of Tn10 insertion mutants defective in enterobacterial common antigen synthesis. J. Biol. Chem. 265 (1990) 13490-13497. [PMID: 2166030]

3. Morgan, P. M., Sala, R. F., and Tanner, M. E. Eliminations in the reactions catalyzed by UDP-N-acetylglucosamine 2-epimerase. J. Am. Chem. Soc. 119 (1997) 10269-10277.

4. Campbell, R.E., Mosimann, S.C., Tanner, M.E. and Strynadka, N.C. The structure of UDP-N-acetylglucosamine 2-epimerase reveals homology to phosphoglycosyl transferases. Biochemistry 39 (2000) 14993-15001. [PMID: 11106477]

5. Samuel, J. and Tanner, M.E. Active site mutants of the "non-hydrolyzing" UDP-N-acetylglucosamine 2-epimerase from Escherichia coli. Biochim. Biophys. Acta 1700 (2004) 85-91. [PMID: 15210128]

6. Soldo, B., Lazarevic, V., Pooley, H.M. and Karamata, D. Characterization of a Bacillus subtilis thermosensitive teichoic acid-deficient mutant: gene mnaA (yvyH) encodes the UDP-N-acetylglucosamine 2-epimerase. J. Bacteriol. 184 (2002) 4316-4320. [PMID: 12107153]

[EC 5.1.3.14 created 1976, modified 2012]

EC 5.1.3.25

Reaction: dTDP-6-deoxy-β-L-talose = dTDP-6-deoxy-β-L-mannose

Glossary: dTDP-6-deoxy-β-L-mannose = dTDP-4-β-L-rhamnose

Other name(s): dTDP-4-L-rhamnose 4-epimerase; wbiB (gene name)

Systematic name: dTDP-6-deoxy-β-L-talose 4-epimerase

Comments: The equilibrium is strongly towards dTDP-6-deoxy-β-L-mannose.

1. Yoo, H.G., Kwon, S.Y., Karki, S. and Kwon, H.J. A new route to dTDP-6-deoxy-L-talose and dTDP-L-rhamnose: dTDP-L-rhamnose 4-epimerase in Burkholderia thailandensis. Bioorg. Med. Chem. Lett. 21 (2011) 3914-3917. [PMID: 21640586]

[EC 5.1.3.25 created 2012]

EC 5.1.99.6

Accepted name: NAD(P)H-hydrate epimerase

Reaction: (1) (6R)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide
(2) (6R)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = (6S)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate

Glossary: 6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide = NADHX = NADH-hydrate
6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide phosphate = NADPHX = NADPH-hydrate

Other name(s): NAD(P)HX epimerase

Systematic name: (6R)-6β-hydroxy-1,4,5,6-tetrahydronicotinamide-adenine dinucleotide 6-epimerase

Comments: The enzyme can use either (R)-NADH-hydrate or (R)-NADPH-hydrate as a substrate. Its physiological role is to convert the (R) forms to the (S) forms, which could then be restored to active dinucleotides by EC 4.2.1.93, ATP-dependent NAD(P)H-hydrate dehydratase.

References:

[EC 5.1.99.6 created 2012]

EC 5.2.1.14

Accepted name: β-carotene isomerase

Reaction: all-trans-β-carotene = 9-cis-β-carotene

Accepted name: methylornithine synthase

Other name(s): DWARF27 (gene name)

Systematic name: β-carotene 9-cis-all-trans isomerase

Comments: The enzyme participates in a pathway leading to biosynthesis of strigolactones, plant hormones involved in promotion of symbiotic associations known as arbuscular mycorrhiza.

References:

1. Lin, H., Wang, R., Qian, Q., Yan, M., Meng, X., Fu, Z., Yan, C., Jiang, B., Su, Z., Li, J. and Wang, Y. DWARF27, an iron-containing protein required for the biosynthesis of strigolactones, regulates rice tiller bud outgrowth. Plant Cell 21 (2009) 1512-1525. [PMID: 19470589]

[EC 5.2.1.14 created 2012]

EC 5.4.99.58

Reaction: L-lysine = (3R)-3-methyl-D-ornithine

Glossary: (3R)-3-methyl-D-ornithine = (2R,3R)-2,5-diamino-3-methylpentanoate

Other name(s): PylB

Systematic name: L-lysine carboxy-aminomethylmutase

Comments: The enzyme is a member of the superfamily of S-adenosyl-L-methionine-dependent radical (radical AdoMet) enzymes. Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The reaction is part of the biosynthesis pathway of pyrrolysine, a naturally occurring amino acid found in some archaeal methyltransferases.