Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are proposed additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Keith Tipton, Sinèad Boyce, Gerry Moss and Hal Dixon, with occasional help from other Committee members, and were put on the web by Gerry Moss. Comments and suggestions on these draft entries should be sent to Professor K.F. Tipton and Dr S. Boyce (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland) The entries were added on the date indicated and fully approved after a month.

Many thanks to those of you who have submitted details of new or missing enzymes, or updates to existing enzymes.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


Contents

EC 1.1.1.296 dihydrocarveol dehydrogenase (21 June 2008)
EC 1.1.1.297 limonene-1,2-diol dehydrogenase (21 June 2008)
*EC 1.1.3.41 alditol oxidase (16 December 2008)
EC 1.2.1.73 sulfoacetaldehyde dehydrogenase (29 July 2008)
EC 1.3.1.81 (+)-pulegone reductase (29 July 2008)
EC 1.3.1.82 (–)-isopiperitenone reductase (17 September, 2008)
EC 1.3.99.25 carvone reductase (21 June 2008)
*EC 1.4.3.4 monoamine oxidase (29 July 2008)
EC 1.4.3.6 deleted now EC 1.4.3.21 and EC 1.4.3.22 (29 July 2008)
*EC 1.4.3.16 L-aspartate oxidase (12 November 2008)
EC 1.4.3.21 primary-amine oxidase (29 July 2008)
EC 1.4.3.22 diamine oxidase (29 July 2008)
EC 1.13.12.15 3,4-dihydroxyphenylalanine oxidative deaminase (12 November 2008)
EC 1.14.13.104 (+)-menthofuran synthase (29 July 2008)
EC 1.14.13.105 monocyclic monoterpene ketone monooxygenase (21 June 2008)
EC 1.14.13.106 epi-isozizaene 5-monooxygenase (16 December 2008)
EC 1.14.19.4 Δ8-fatty-acid desaturase (29 July 2008)
EC 1.14.19.5 Δ11-fatty-acid desaturase (13 September, 2008)
EC 1.14.19.6 Δ12-fatty-acid desaturase (13 September, 2008)
EC 1.14.21.7 biflaviolin synthase (16 December 2008)
EC 2.1.3.10 malonyl-S-ACP:biotin-protein carboxyltransferase (25 November 2008)
EC 2.1.3.11 N-succinylornithine carbamoyltransferase (12 November 2008)
EC 2.2.1.9 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase (11 June 2008)
*EC 2.3.1.39 [acyl-carrier-protein] S-malonyltransferase (25 November 2008)
*EC 2.3.1.94 6-deoxyerythronolide-B synthase (12 November 2008)
EC 2.3.1.187 acetyl-S-ACP:malonate ACP transferase (25 November 2008)
*EC 2.4.1.14 sucrose-phosphate synthase (16 December 2008)
EC 2.4.1.245 α,α-trehalose synthase (29 July 2008)
EC 2.5.1.64 transferred to EC 2.2.1.9 and EC 4.2.99.20
EC 2.5.1.72 quinolinate synthase (14 November 2008)
*EC 2.7.7.61 citrate lyase holo-[acyl-carrier protein] synthase (21 June 2008)
EC 2.7.7.66 malonate decarboxylase holo-[acyl-carrier protein] synthase (21 June 2008)
*EC 2.7.8.25 triphosphoribosyl-dephospho-CoA synthase (21 June 2008)
EC 3.1.1.83 monoterpene ε-lactone hydrolase (21 June 2008)
*EC 3.1.3.24 sucrose-phosphate phosphatase (16 December 2008)
EC 3.1.3.78 phosphatidylinositol-4,5-bisphosphate 4-phosphatase (12 November 2008)
EC 3.1.4.53 3',5'-cyclic-AMP phosphodiesterase (21 June 2008)
EC 3.1.7.4 sclareol cyclase (21 June 2008)
EC 3.1.26.12 ribonuclease E (29 July 2008)
*EC 3.2.1.97 glycopeptide α-N-acetylgalactosaminidase (16 December 2008)
EC 3.2.1.110 deleted identical to EC 3.2.1.97(16 December 2008)
EC 3.2.2.26 futalosine hydrolase (12 November 2008)
EC 3.4.11.24 aminopeptidase S (29 July 2008)
*EC 3.5.1.77 N-carbamoyl-D-amino-acid hydrolase (12 November 2008)
*EC 3.5.1.87 N-carbamoyl-L-amino-acid hydrolase (12 November 2008)
EC 3.6.1.53 Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase (12 November 2008)
EC 4.1.1.87 malonyl-S-ACP decarboxylase (25 November 2008)
EC 4.1.1.88 biotin-independent malonate decarboxylase (25 November 2008)
EC 4.1.1.89 biotin-dependent malonate decarboxylase (25 November 2008)
EC 4.1.2.43 3-hexulose-6-phosphate synthase (12 November 2008)
*EC 4.2.1.92 hydroperoxide dehydratase (12 November 2008)
EC 4.2.3.36 terpentetriene synthase (21 June 2008)
EC 4.2.3.37 epi-isozizaene synthase (16 December 2008)
EC 4.2.99.20 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (21 June 2008)
EC 4.3.99.2 carboxybiotin decarboxylase (25 November 2008)
EC 5.1.99.5 hydantoin racemase (12 November 2008)
EC 5.3.1.27 6-phospho-3-hexuloisomerase (12 November 2008)
EC 5.5.1.15 terpentedienyl-diphosphate synthase (21 June 2008)
EC 5.5.1.16 halimadienyl-diphosphate synthase (21 June 2008)
EC 6.2.1.35 ACP-SH:acetate ligase (25 November 2008)

EC 1.1.1.296

Accepted name: dihydrocarveol dehydrogenase

Reaction: ment-8-en-2-ol + NAD+ = meth-8-en-2-one + NADH + H+

Glossary: (+)-dihydrocarveol = (1S,2S,4S)-menth-8-en-2-ol
(+)-isodihydrocarveol = (1S,2S,4R)-menth-8-en-2-ol
(+)-neoisodihydrocarveol = (1S,2R,4R)-menth-8-en-2-ol
(–)-dihydrocarvone = (1S,4S)-menth-8-en-2-one
(+)-isodihydrocarvone = (1S,4R)-menth-8-en-2-one

Other name(s): carveol dehydrogenase

Systematic name: menth-8-en-2-ol:NAD+ oxidoreductase

Comments: This enzyme from the the Gram-positive bacterium Rhodococcus erythropolis DCL14 forms part of the carveol and dihydrocarveol degradation pathway. The enzyme accepts all eight stereoisomers of menth-8-en-2-ol as substrate, although some isomers are converted faster than others. The preferred substrates are (+)-neoisodihydrocarveol, (+)-isodihydrocarveol, (+)-dihydrocarveol and (–)-isodihydrocarveol.

References:

1. van der Werf, M.J. and Boot, A.M. Metabolism of carveol and dihydrocarveol in Rhodococcus erythropolis DCL14. Microbiology 146 (2000) 1129-1141. [PMID: 10832640]

[EC 1.1.1.296 created 2008]

EC 1.1.1.297

Accepted name: limonene-1,2-diol dehydrogenase

Reaction: menth-8-ene-1,2-diol + NAD+ = 1-hydroxymenth-8-en-2-one + NADH + H+ (general reaction)
(1) (1S,2S,4R)-menth-8-ene-1,2-diol + NAD+ = (1S,4R)-1-hydroxymenth-8-en-2-one + NADH + H+
(2) (1R,2R,4S)-menth-8-ene-1,2-diol + NAD+ = (1R,4S)-1-hydroxymenth-8-en-2-one + NADH + H+

Glossary: limonene-1,2-diol = menth-8-ene-1,2-diol = 1-methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol

Other name(s): NAD+-dependent limonene-1,2-diol dehydrogenase

Systematic name: menth-8-ene-1,2-diol:NADP+ oxidoreductase

Comments: While the enzyme from the Gram-positive bacterium Rhodococcus erythropolic DCL14 can use both (1S,2S,4R)- and (1R,2R,4S)-menth-8-ene-1,2-diol as substrate, activity is higher with (1S,2S,4R)-menth-8-ene-1,2-diol as substrate.

References:

1. van der Werf, M.J., Swarts, H.J. and de Bont, J.A. Rhodococcus erythropolis DCL14 contains a novel degradation pathway for limonene. Appl. Environ. Microbiol. 65 (1999) 2092-2102. [PMID: 10224006]

[EC 1.1.1.297 created 2008]

*EC 1.1.3.41

Accepted name: alditol oxidase

Reaction: an alditol + O2 = an aldose + H2O2

Other name(s): xylitol oxidase; xylitol:oxygen oxidoreductase; AldO

Systematic name: alditol:oxygen oxidoreductase

Comments: The enzyme from Streptomyces sp. IKD472 and from Streptomyces coelicolor is a monomeric oxidase containing one molecule of FAD per molecule of protein [1,2]. While xylitol (five carbons) and sorbitol (6 carbons) are the preferred substrates, other alditols, including L-threitol (four carbons), D-arabitol (five carbons), D-galactitol (six carbons) and D-mannitol (six carbons) can also act as substrates, but more slowly [1,2]. Belongs in the vanillyl-alcohol-oxidase family of enzymes [2].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 177322-52-0

References:

1. Yamashita, M., Omura, H., Okamoto, E., Furuya, Y., Yabuuchi, M., Fukahi, K. and Murooka, Y. Isolation, characterization, and molecular cloning of a thermostable xylitol oxidase from Streptomyces sp. IKD472. J. Biosci. Bioeng. 89 (2000) 350-360. [PMID: 16232758]

2. Heuts, D.P., van Hellemond, E.W., Janssen, D.B. and Fraaije, M.W. Discovery, characterization, and kinetic analysis of an alditol oxidase from Streptomyces coelicolor. J. Biol. Chem. 282 (2007) 20283-20291. [PMID: 17517896]

3. Forneris, F., Heuts, D.P., Delvecchio, M., Rovida, S., Fraaije, M.W. and Mattevi, A. Structural analysis of the catalytic mechanism and stereoselectivity in Streptomyces coelicolor alditol oxidase. Biochemistry 47 (2008) 978-985. [PMID: 18154360]

[EC 1.1.3.41 created 2002]

EC 1.2.1.73

Accepted name: sulfoacetaldehyde dehydrogenase

Reaction: 2-sulfoacetaldehyde + H2O + NAD+ = sulfoacetate + NADH + 2 H+

Glossary: 2-sulfoacetaldehyde = 2-oxoethanesulfonate
taurine = 2-aminoethanesulfonate

Other name(s): SafD

Systematic name: 2-sulfoacetaldehyde:NAD+ oxidoreductase

Comments: This reaction is part of a bacterial pathway that can utilize the amino group of taurine as a sole source of nitrogen for growth. At physiological concentrations, NAD+ cannot be replaced by NADP+. The enzyme is specific for sulfoacetaldehyde, as formaldehyde, acetaldehyde, betaine aldehyde, propanal, glyceraldehyde, phosphonoacetaldehyde, glyoxylate, glycolaldehyde and 2-oxobutyrate are not substrates.

References:

1. Krejčík, Z., Denger, K., Weinitschke, S., Hollemeyer, K., Pačes, V., Cook, A.M. and Smits, T.H.M. Sulfoacetate released during the assimilation of taurine-nitrogen by Neptuniibacter caesariensis: purification of sulfoacetaldehyde dehydrogenase. Arch. Microbiol. 190 (2008) 159-168. [PMID: 18506422]

Note For the reference an accent may not be seen. č is c-hacek.

[EC 1.2.1.73 created 2008]

EC 1.3.1.81

Accepted name: (+)-pulegone reductase

Reaction: (1) (–)-menthone + NADP+ = (+)-pulegone + NADPH + H+
(2) (+)-isomenthone + NADP+ = (+)-pulegone + NADPH + H+

Systematic name: (–)-menthone:NADP+ oxidoreductase

Comments: NADH cannot replace NADPH as reductant. The Δ8,9-double bond of (+)-cis-isopulegone and the Δ1,2-double bond of (±)-piperitone are not substrates. The enzyme from peppermint (Mentha x piperita) converts (+)-pulegone into both (–)-menthone and (+)-isomenthone at a ratio of 70:30 for native enzyme but it does not catalyse the reverse reaction. This enzyme is a member of the medium-chain dehydrogenase/reductase superfamily.

References:

1. Ringer, K.L., McConkey, M.E., Davis, E.M., Rushing, G.W. and Croteau, R. Monoterpene double-bond reductases of the (–)-menthol biosynthetic pathway: isolation and characterization of cDNAs encoding (–)-isopiperitenone reductase and (+)-pulegone reductase of peppermint. Arch. Biochem. Biophys. 418 (2003) 80-92. [PMID: 13679086]

[EC 1.3.1.81 created 2008]

EC 1.3.1.82

Accepted name: (–)-isopiperitenone reductase

Reaction: (+)-cis-isopulegone + NADP+ = (–)-isopiperitenone + NADPH + H+

Systematic name: (+)-cis-isopulegone:NADP+ oxidoreductase

Comments: The reaction occurs in the opposite direction to that shown above. The enzyme participates in the menthol-biosynthesis pathway of Mentha plants. (+)-Pulegone, (+)-cis-isopulegone and (–)-menthone are not substrates. The enzyme has a preference for NADPH as the reductant, with NADH being a poor substitute [2]. The enzyme is highly regioselective for the reduction of the endocyclic 1,2-double bond, and is stereoselective, producing only the 1R-configured product. It is a member of the short-chain dehydrogenase/reductase superfamily.

References:

1. Croteau, R. and Venkatachalam, K.V. Metabolism of monoterpenes: demonstration that (+)-cis-isopulegone, not piperitenone, is the key intermediate in the conversion of (–)-isopiperitenone to (+)-pulegone in peppermint (Mentha piperita). Arch. Biochem. Biophys. 249 (1986) 306-315. [PMID: 3755881]

2. Ringer, K.L., McConkey, M.E., Davis, E.M., Rushing, G.W. and Croteau, R. Monoterpene double-bond reductases of the (–)-menthol biosynthetic pathway: isolation and characterization of cDNAs encoding (–)-isopiperitenone reductase and (+)-pulegone reductase of peppermint. Arch. Biochem. Biophys. 418 (2003) 80-92. [PMID: 13679086]

[EC 1.3.1.82 created 2008]

EC 1.3.99.25

Accepted name: carvone reductase

Reaction: (1) (+)-dihydrocarvone + acceptor = (–)-carvone + reduced acceptor
(2) (–)-isodihydrocarvone + acceptor = (+)-carvone + reduced acceptor

Glossary: (+)-dihydrocarvone = (1S,4R)-menth-8-en-2-one
(+)-isodihydrocarvone = (1S,4R)-menth-8-en-2-one
(–)-carvone = (4R)-mentha-1(6),8-dien-6-one = (5R)-2-methyl-5-(prop-1-en-2-yl)cyclohex-2-en-1-one

Systematic name: (+)-dihydrocarvone:acceptor 1,6-oxidoreductase

Comments: This enzyme participates in the carveol and dihydrocarveol degradation pathway of the Gram-positive bacterium Rhodococcus erythropolis DCL14. The enzyme has not been purified, and requires an unknown cofactor, which is different from NAD+, NADP+ or a flavin.

References:

1. van der Werf, M.J. and Boot, A.M. Metabolism of carveol and dihydrocarveol in Rhodococcus erythropolis DCL14. Microbiology 146 (2000) 1129-1141. [PMID: 10832640]

[EC 1.3.99.25 created 2008]

*EC 1.4.3.4

Accepted name: monoamine oxidase

Reaction: RCH2NHR' + H2O + O2 = RCHO + R'NH2 + H2O2

Other name(s): adrenalin oxidase; adrenaline oxidase; amine oxidase (ambiguous); amine oxidase (flavin-containing); amine:oxygen oxidoreductase (deaminating) (flavin-containing); epinephrine oxidase; MAO; MAO A; MAO B; MAO-A; MAO-B; monoamine oxidase A; monoamine oxidase B; monoamine:O2 oxidoreductase (deaminating); polyamine oxidase (ambiguous); serotonin deaminase; spermidine oxidase (ambiguous); spermine oxidase (ambiguous); tyraminase; tyramine oxidase

Systematic name: amine:oxygen oxidoreductase (deaminating)

Comments: A mitochondrial outer-membrane flavoprotein (FAD) that catalyses the oxidative deamination of neurotransmitters and biogenic amines [3]. Acts on primary amines, and also on some secondary and tertiary amines. It differs from EC 1.4.3.21, primary-amine oxidase as it can oxidize secondary and tertiary amines but not methylamine. This enzyme is inhibited by acetylenic compounds such as chlorgyline, 1-deprenyl and pargyline but, unlike EC 1.4.3.21 and EC 1.4.3.22 (diamine oxidase), it is not inhibited by semicarbazide.

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 9001-66-5

References:

1. Blaschko, H. Amine oxidase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 8, Academic Press, New York, 1963, pp. 337-351.

2. Dostert, P.L., Strolin Benedetti, M. and Tipton, K.F. Interactions of monoamine oxidase with substrates and inhibitors. Med. Res. Rev. 9 (1989) 45-89. [PMID: 2644497]

3. Edmondson, D.E., Mattevi, A., Binda, C., Li, M. and Hubálek, F. Structure and mechanism of monoamine oxidase. Curr. Med. Chem. 11 (2004) 1983-1993. [PMID: 15279562]

4. Shih, J.C. and Chen, K. Regulation of MAO-A and MAO-B gene expression. Curr. Med. Chem. 11 (2004) 1995-2005. [PMID: 15279563]

5. Tipton, K.F., Boyce, S., O'Sullivan, J., Davey, G.P. and Healy, J. Monoamine oxidases: certainties and uncertainties. Curr. Med. Chem. 11 (2004) 1965-1982. [PMID: 15279561]

6. De Colibus, L., Li, M., Binda, C., Lustig, A., Edmondson, D.E. and Mattevi, A. Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B. Proc. Natl. Acad. Sci. USA 102 (2005) 12684-12689. [PMID: 16129825]

7. Youdim, M.B., Edmondson, D. and Tipton, K.F. The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci. 7 (2006) 295-309. [PMID: 16552415]

8. Youdim, M.B. and Bakhle, Y.S. Monoamine oxidase: isoforms and inhibitors in Parkinson's disease and depressive illness. Br. J. Pharmacol. 147 Suppl. 1 (2006) S287-S296. [PMID: 16402116]

[EC 1.4.3.4 created 1961, modified 1983 (EC 1.4.3.9 created 1972, incorporated 1984), modified 2008]

[EC 1.4.3.6 Deleted entry: amine oxidase (copper-containing). This was classified on the basis of cofactor content rather than reaction catalysed and is now known to contain two distinct enzyme activities. It has been replaced by two enzymes, EC 1.4.3.21 (primary-amine oxidase) and EC 1.4.3.22 (diamine oxidase) (EC 1.4.3.6 created 1961, modified 1983, modified 1989, deleted 2008)]

*EC 1.4.3.16

Accepted name: L-aspartate oxidase

Reaction: L-aspartate + O2 = iminosuccinate + H2O2

Other name(s): NadB; Laspo; AO

Systematic name: L-aspartate:oxygen oxidoreductase (deaminating)

Comments: A flavoprotein (FAD). L-Aspartate oxidase catalyses the first step in the de novo biosynthesis of NAD+ in some bacteria. O2 can be replaced by fumarate as electron acceptor, yielding succinate [5]. The ability of the enzyme to use both O2 and fumarate in cofactor reoxidation enables it to function under both aerobic and anaerobic conditions [5]. Iminosuccinate can either be hydrolysed to form oxaloacetate and NH3 or can be used by EC 2.5.1.72, quinolinate synthase, in the production of quinolinate. The enzyme is a member of the succinate dehydrogenase/fumarate-reductase family of enzymes [5].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 69106-47-4

References:

1. Nasu, S., Wicks, F.D. and Gholson, R.K. L-Aspartate oxidase, a newly discovered enzyme of Escherichia coli, is the B protein of quinolinate synthetase. J. Biol. Chem. 257 (1982) 626-632. [PMID: 7033218]

2. Mortarino, M., Negri, A., Tedeschi, G., Simonic, T., Duga, S., Gassen, H.G. and Ronchi, S. L-aspartate oxidase from Escherichia coli. I. Characterization of coenzyme binding and product inhibition. Eur. J. Biochem. 239 (1996) 418-426. [PMID: 8706749]

3. Tedeschi, G., Negri, A., Mortarino, M., Ceciliani, F., Simonic, T., Faotto, L. and Ronchi, S. L-Aspartate oxidase from Escherichia coli. II. Interaction with C4 dicarboxylic acids and identification of a novel L-aspartate: fumarate oxidoreductase activity. Eur. J. Biochem. 239 (1996) 427-433. [PMID: 8706750]

4. Mattevi, A., Tedeschi, G., Bacchella, L., Coda, A., Negri, A. and Ronchi, S. Structure of L-aspartate oxidase: implications for the succinate dehydrogenase/fumarate reductase oxidoreductase family. Structure 7 (1999) 745-756. [PMID: 10425677]

5. Bossi, R.T., Negri, A., Tedeschi, G. and Mattevi, A. Structure of FAD-bound L-aspartate oxidase: insight into substrate specificity and catalysis. Biochemistry 41 (2002) 3018-3024. [PMID: 11863440]

6. Katoh, A., Uenohara, K., Akita, M. and Hashimoto, T. Early steps in the biosynthesis of NAD in Arabidopsis start with aspartate and occur in the plastid. Plant Physiol. 141 (2006) 851-857. [PMID: 16698895]

[EC 1.4.3.16 created 1984, modified 2008]

EC 1.4.3.21

Accepted name: primary-amine oxidase

Reaction: RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2

Other name(s): amine oxidase (ambiguous); amine oxidase (copper-containing); amine oxidase (pyridoxal containing) (incorrect); benzylamine oxidase (incorrect); CAO (ambiguous); copper amine oxidase (ambiguous); Cu-amine oxidase (ambiguous); Cu-containing amine oxidase (ambiguous); diamine oxidase (incorrect); diamino oxhydrase (incorrect); histamine deaminase (ambiguous); histamine oxidase (ambiguous); monoamine oxidase (ambiguous); plasma monoamine oxidase (ambiguous); polyamine oxidase (ambiguous); semicarbazide-sensitive amine oxidase (ambiguous); SSAO (ambiguous)

Systematic name: primary-amine:oxygen oxidoreductase (deaminating)

Comments: A group of enzymes that oxidize primary monoamines but have little or no activity towards diamines, such as histamine, or towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, unlike EC 1.4.3.4, monoamine oxidase, are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide. In some mammalian tissues the enzyme also functions as a vascular-adhesion protein (VAP-1).

References:

1. Haywood, G.W. and Large, P.J. Microbial oxidation of amines. Distribution, purification and properties of two primary-amine oxidases from the yeast Candida boidinii grown on amines as sole nitrogen source. Biochem. J. 199 (1981) 187-201. [PMID: 7337701]

2. Tipping, A.J. and McPherson, M.J. Cloning and molecular analysis of the pea seedling copper amine oxidase. J. Biol. Chem. 270 (1995) 16939-16946. [PMID: 7622512]

3. Lyles, G.A. Mammalian plasma and tissue-bound semicarbazide-sensitive amine oxidases: biochemical, pharmacological and toxicological aspects. Int. J. Biochem. Cell Biol. 28 (1996) 259-274. [PMID: 8920635]

4. Wilce, M.C., Dooley, D.M., Freeman, H.C., Guss, J.M., Matsunami, H., McIntire, W.S., Ruggiero, C.E., Tanizawa, K. and Yamaguchi, H. Crystal structures of the copper-containing amine oxidase from Arthrobacter globiformis in the holo and apo forms: implications for the biogenesis of topaquinone. Biochemistry 36 (1997) 16116-16133. [PMID: 9405045]

5. Lee, Y. and Sayre, L.M. Reaffirmation that metabolism of polyamines by bovine plasma amine oxidase occurs strictly at the primary amino termini. J. Biol. Chem. 273 (1998) 19490-19494. [PMID: 9677370]

6. Houen, G. Mammalian Cu-containing amine oxidases (CAOs): new methods of analysis, structural relationships, and possible functions. APMIS Suppl. 96 (1999) 1-46. [PMID: 10668504]

7. Andrés, N., Lizcano, J.M., Rodríguez, M.J., Romera, M., Unzeta, M. and Mahy, N. Tissue activity and cellular localization of human semicarbazide-sensitive amine oxidase. J. Histochem. Cytochem. 49 (2001) 209-217. [PMID: 11156689]

8. Saysell, C.G., Tambyrajah, W.S., Murray, J.M., Wilmot, C.M., Phillips, S.E., McPherson, M.J. and Knowles, P.F. Probing the catalytic mechanism of Escherichia coli amine oxidase using mutational variants and a reversible inhibitor as a substrate analogue. Biochem. J. 365 (2002) 809-816. [PMID: 11985492]

9. O'Sullivan, J., Unzeta, M., Healy, J., O'Sullivan, M.I., Davey, G. and Tipton, K.F. Semicarbazide-sensitive amine oxidases: enzymes with quite a lot to do. Neurotoxicology 25 (2004) 303-315. [PMID: 14697905]

10. Airenne, T.T., Nymalm, Y., Kidron, H., Smith, D.J., Pihlavisto, M., Salmi, M., Jalkanen, S., Johnson, M.S. and Salminen, T.A. Crystal structure of the human vascular adhesion protein-1: unique structural features with functional implications. Protein Sci. 14 (2005) 1964-1974. [PMID: 16046623]

[EC 1.4.3.21 created 2007 (EC 1.4.3.6 created 1961, part-incorporated 2008)]

EC 1.4.3.22

Accepted name: diamine oxidase

Reaction: histamine + H2O + O2 = (imidazol-4-yl)acetaldehyde + NH3 + H2O2

Other name(s): amine oxidase (ambiguous); amine oxidase (copper-containing) (ambiguous); CAO (ambiguous); Cu-containing amine oxidase (ambiguous); copper amine oxidase (ambiguous); diamine oxidase (ambiguous); diamino oxhydrase (ambiguous); histaminase; histamine deaminase (incorrect); semicarbazide-sensitive amine oxidase (incorrect); SSAO (incorrect)

Systematic name: histamine:oxygen oxidoreductase (deaminating)

Comments: A group of enzymes that oxidize diamines, such as histamine, and also some primary monoamines but have little or no activity towards secondary and tertiary amines. They are copper quinoproteins (2,4,5-trihydroxyphenylalanine quinone) and, like EC 1.4.3.21 (primary-amine oxidase) but unlike EC 1.4.3.4 (monoamine oxidase), they are sensitive to inhibition by carbonyl-group reagents, such as semicarbazide.

References:

1. Zeller, E.A. Diamine oxidases. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 8, Academic Press, New York, 1963, pp. 313-335.

2. Crabbe, M.J., Waight, R.D., Bardsley, W.G., Barker, R.W., Kelly, I.D. and Knowles, P.F. Human placental diamine oxidase. Improved purification and characterization of a copper- and manganese-containing amine oxidase with novel substrate specificity. Biochem. J. 155 (1976) 679-687. [PMID: 182134]

3. Chassande, O., Renard, S., Barbry, P. and Lazdunski, M. The human gene for diamine oxidase, an amiloride binding protein. Molecular cloning, sequencing, and characterization of the promoter. J. Biol. Chem. 269 (1994) 14484-14489. [PMID: 8182053]

4. Houen, G. Mammalian Cu-containing amine oxidases (CAOs): new methods of analysis, structural relationships, and possible functions. APMIS Suppl. 96 (1999) 1-46. [PMID: 10668504]

5. Elmore, B.O., Bollinger, J.A. and Dooley, D.M. Human kidney diamine oxidase: heterologous expression, purification, and characterization. J. Biol. Inorg. Chem. 7 (2002) 565-579. [PMID: 12072962]

[EC 1.4.3.22 created 2007 (EC 1.4.3.6 created 1961, part-incorporated 2008)]

EC 1.13.12.15

Accepted name: 3,4-dihydroxyphenylalanine oxidative deaminase

Reaction: 2 3,4-dihydroxy-L-phenylalanine + O2 = 2 3,4-dihydroxyphenylpyruvate + 2 NH3

Glossary: DOPA = L-dopa = 3,4-dihydroxy-L-phenylalanine

Other name(s): 3,4-dihydroxy-L-phenylalanine: oxidative deaminase; oxidative deaminase; DOPA oxidative deaminase; DOPAODA

Systematic name: 3,4-dihydroxy-L-phenylalanine:oxygen oxidoreductase (deaminating)

Comments: This enzyme is one of the three enzymes involved in DOPA (3,4-dihydroxyphenylalanine) catabolism in the non-oxygenic phototrophic bacterium Rubrivivax benzoatilyticus OU5 (and not Rhodobacter sphaeroides OU5 as had been thought [1]), the other two being EC 4.3.1.22 (dihydroxyphenylalanine reductive deaminase) and EC 2.6.1.49 (3,4-dihydroxyphenylalanine transaminase). In addition to DOPA, the enzyme can also use L-tyrosine, L-phenylalanine, L-tryptophan and glutamate as substrate, but more slowly. The enzyme is inhibited by NADH and 2-oxoglutarate.

References:

1. Ranjith, N.K., Ramana, Ch.V. and Sasikala, Ch. Purification and characterization of 3,4-dihydroxyphenylalanine oxidative deaminase from Rhodobacter sphaeroides OU5. Can. J. Microbiol. 54 (2008) 829-834.

[EC 1.13.12.15 created 2008]

EC 1.14.13.104

Accepted name: (+)-menthofuran synthase

Reaction: (+)-pulegone + NADPH + H+ + O2 = (+)-menthofuran + NADP+ + H2O

Other name(s): menthofuran synthase; (+)-pulegone 9-hydroxylase; (+)-MFS; cytochrome P450 menthofuran synthase

Systematic name: (+)-pulegone,NADPH:oxygen oxidoreductase (9-hydroxylating)

Comments: A heme-thiolate protein (P-450). The conversion of substrate into product involves the hydroxylation of the syn-methyl (C9), intramolecular cyclization to the hemiketal and dehydration to the furan [1]. This is the second cytochrome P-450-mediated step of monoterpene metabolism in peppermint, with the other step being catalysed by EC 1.14.13.47, (S)-limonene 3-monooxygenase [1].

References:

1. Bertea, C.M., Schalk, M., Karp, F., Maffei, M. and Croteau, R. Demonstration that menthofuran synthase of mint (Mentha) is a cytochrome P450 monooxygenase: cloning, functional expression, and characterization of the responsible gene. Arch. Biochem. Biophys. 390 (2001) 279-286. [PMID: 11396930]

2. Mahmoud, S.S. and Croteau, R.B. Menthofuran regulates essential oil biosynthesis in peppermint by controlling a downstream monoterpene reductase. Proc. Natl. Acad. Sci. USA 100 (2003) 14481-14486. [PMID: 14623962]

[EC 1.14.13.104 created 2008]

EC 1.14.13.105

Accepted name: monocyclic monoterpene ketone monooxygenase

Reaction: (1) (–)-menthone + NADPH + H+ + O2 = (4R,7S)-7-isopropyl-4-methyloxepan-2-one + NADP+ + H2O
(2) dihydrocarvone + NADPH + H+ + O2 = 4-isopropenyl-7-methyloxepan-2-one + NADP+ + H2O
(3) (iso)-dihydrocarvone + NADPH + H+ + O2 = 6-isopropenyl-3-methyloxepan-2-one + NADP+ + H2O
(4a) 1-hydroxymenth-8-en-2-one + NADPH + H+ + O2 = 7-hydroxy-4-isopropenyl-7-methyloxepan-2-one + NADP+ + H2O
(4b) 7-hydroxy-4-isopropenyl-7-methyloxepan-2-one = 3-isopropenyl-6-oxoheptanoate (spontaneous)

Other name(s): 1-hydroxy-2-oxolimonene 1,2-monooxygenase; dihydrocarvone 1,2-monooxygenase; MMKMO

Systematic name: (–)-menthone,NADPH:oxygen oxidoreductase

Comments: A flavoprotein (FAD). This Baeyer-Villiger monooxygenase enzyme from the Gram-positive bacterium Rhodococcus erythropolis DCL14 has wide substrate specificity, catalysing the lactonization of a large number of monocyclic monoterpene ketones and substituted cyclohexanones [2]. Both (1R,4S)- and (1S,4R)-1-hydroxymenth-8-en-2-one are metabolized, with the lactone product spontaneously rearranging to form 3-isopropenyl-6-oxoheptanoate [1].

References:

1. van der Werf, M.J., Swarts, H.J. and de Bont, J.A. Rhodococcus erythropolis DCL14 contains a novel degradation pathway for limonene. Appl. Environ. Microbiol. 65 (1999) 2092-2102. [PMID: 10224006]

2. Van Der Werf, M.J. Purification and characterization of a Baeyer-Villiger mono-oxygenase from Rhodococcus erythropolis DCL14 involved in three different monocyclic monoterpene degradation pathways. Biochem. J. 347 (2000) 693-701. [PMID: 10769172]

3. van der Werf, M.J. and Boot, A.M. Metabolism of carveol and dihydrocarveol in Rhodococcus erythropolis DCL14. Microbiology 146 (2000) 1129-1141. [PMID: 10832640]

[EC 1.14.13.105 created 2008]

EC 1.14.13.106

Accepted name: epi-isozizaene 5-monooxygenase

Reaction: (1a) (+)-epi-isozizaene + NADPH + H+ + O2 = (5S)-albaflavenol + NADP+ + H2O
(1b) (5S)-albaflavenol + NADPH + H+ + O2 = albaflavenone + NADP+ + 2 H2O
(2a) (+)-epi-isozizaene + NADPH + H+ + O2 = (5R)-albaflavenol + NADP+ + H2O
(2b) (5R)-albaflavenol + NADPH + H+ + O2 = albaflavenone + NADP+ + 2 H2O

For diagram of reaction, click here

Glossary: for epi-isozizaene click here.

Other name(s): CYP170A1

Systematic name: (+)-epi-isozizaene,NADPH:oxygen oxidoreductase (5-hydroxylating)

Comments: This cytochrome-P450 enzyme, from the soil-dwelling bacterium Streptomyces coelicolor A3(2), catalyses two sequential allylic oxidation reactions. The substrate epi-isozizaene, which is formed by the action of EC 4.2.3.37, epi-isozizaene synthase, is first oxidized to yield the epimeric intermediates (4R)-albaflavenol and (4S)-albaflavenol, which can be further oxidized to yield the sesquiterpenoid antibiotic albaflavenone.

References:

1. Zhao, B., Lin, X., Lei, L., Lamb, D.C., Kelly, S.L., Waterman, M.R. and Cane, D.E. Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor A3(2). J. Biol. Chem. 283 (2008) 8183-8189. [PMID: 18234666]

[EC 1.14.13.106 created 2008]

EC 1.14.19.4

Accepted name: Δ8-fatty-acid desaturase

Reaction: phytosphinganine + reduced acceptor + O2 = Δ8-phytosphingenine + acceptor + 2 H2O

Glossary: phytosphinganine = 4-hydroxysphinganine

Other name(s): Δ8-sphingolipid desaturase; EFD1; BoDES8; SLD; Δ8 fatty acid desaturase; Δ8-desaturase

Systematic name: phytosphinganine,hydrogen donor:oxygen Δ8-oxidoreductase

Comments: This enzyme, which has been found mainly in plants, introduces a double bond at Δ8 of C18 and C20 fatty acids [2]. The enzyme from the marine microalga Euglena gracilis requires a double bond to be present at Δ11 and is most active with 20:3 Δ11,14,17 and 20:2 Δ11,14 as substrates, although it can also desaturate 20:1 Δ11 [1]. The Δ8-desaturation pathway represents an alternate pathway for the synthesis of the polyunsaturated fatty acids arachidonate (C20:4 Δ5,14) and eicosapentaenoate (C20:5 Δ5,17) in organisms lacking a Δ6-desaturase [1]. The enzyme from the sunflower Helianthus annuus and from the herb Borago officinalis comprises a C-terminal desaturase domain and an N-terminal cytochrome-b5 domain [2].

References:

1. Wallis, J.G. and Browse, J. The Δ8-desaturase of Euglena gracilis: an alternate pathway for synthesis of 20-carbon polyunsaturated fatty acids. Arch. Biochem. Biophys. 365 (1999) 307-316. [PMID: 10328826]

2. Sperling, P., Libisch, B., Zähringer, U., Napier, J.A. and Heinz, E. Functional identification of a Δ8-sphingolipid desaturase from Borago officinalis. Arch. Biochem. Biophys. 388 (2001) 293-298. [PMID: 11368168]

3. Takakuwa, N., Kinoshita, M., Oda, Y. and Ohnishi, M. Isolation and characterization of the genes encoding Δ8-sphingolipid desaturase from Saccharomyces kluyveri and Kluyveromyces lactis. Curr. Microbiol. 45 (2002) 459-461. [PMID: 12402089]

4. Beckmann, C., Rattke, J., Oldham, N.J., Sperling, P., Heinz, E. and Boland, W. Characterization of a Δ8-sphingolipid desaturase from higher plants: a stereochemical and mechanistic study on the origin of E,Z isomers. Angew. Chem. Int. Ed. Engl. 41 (2002) 2298-2300. [PMID: 12203571]

[EC 1.14.19.4 created 2008]

EC 1.14.19.5

Accepted name: Δ11-fatty-acid desaturase

Reaction: acyl-CoA + reduced acceptor + O2 = Δ11-acyl-CoA + acceptor + 2 H2O

Other name(s): Δ11 desaturase; fatty acid Δ11-desaturase; TpDESN; Cro-PG; Δ11 fatty acid desaturase; Z/E11-desaturase; Δ11-palmitoyl-CoA desaturase

Systematic name: acyl-CoA,hydrogen donor:oxygen Δ11-oxidoreductase

Comments: In common with front-end desaturases involved in the synthesis of polyunsaturated fatty acids (PUFAs), this membrane-bound enzyme has a cytochrome b5-like domain at the N-terminus and contains three histidine boxes that are critical for desaturase activity [1]. The enzyme from the marine microalga Thalassiosira pseudonana specifically desaturates palmitic acid 16:0 to 16:1Δ11 [1] whereas that from the leafroller moth Choristoneura rosaceana desaturates myristic acid 14:0 to 14:1Δ11 [2]. 16:1Δ11 represents an important precursor for pheromone synthesis in insect cells, although its function in microalgae is currently unknown [1]. The enzyme from the Egyptian cotton leafworm Spodoptera littoralis has a preference for palmitoyl-CoA as substrate and for NADH rather than NADPH as reduced acceptor [3].

References:

1. Tonon, T., Harvey, D., Qing, R., Li, Y., Larson, T.R. and Graham, I.A. Identification of a fatty acid Δ11-desaturase from the microalga Thalassiosira pseudonana. FEBS Lett. 563 (2004) 28-34. [PMID: 15063718]

2. Hao, G., O'Connor, M., Liu, W. and Roelofs, W.L. Characterization of Z/E11- and Z9-desaturases from the obliquebanded leafroller moth, Choristoneura rosaceana. J. Insect Sci. 2:26 (2002) 1-7.

3. Rodriguez, F., Hallahan, D.L., Pickett, J.A. and Camps, F. Characterization of the Δ11-palmitoyl-CoA-desaturase from Spodoptera littoralis (Lepidoptera:Noctuidae). Insect Biochem. Mol. Biol. 22 (1992) 143-148.

[EC 1.14.19.5 created 2008]

EC 1.14.19.6

Accepted name: Δ12-fatty-acid desaturase

Reaction: acyl-CoA + reduced acceptor + O2 = Δ12-acyl-CoA + acceptor + 2 H2O

Glossary: oleoyl-CoA = cis-octadec-9-enoyl-CoA = (9Z)-octadec-9-enoyl-CoA = 18:1 cis-9 = 18:1(n-9)
linoleoyl-CoA = cis,cis-octadeca-9,12-dienoyl-CoA = (9Z,12Z)-octadeca-9,12-dienoyl-CoA = 18:2(n-6)

Other name(s): Δ12 fatty acid desaturase; Δ126)-desaturase; oleoyl-CoA Δ12 desaturase; Δ12 desaturase; Δ12-desaturase

Systematic name: acyl-CoA,hydrogen donor:oxygen Δ12-oxidoreductase

Comments: In the yeast Lipomyces starkeyi [3] and in the American cockroach [1], this microsomal enzyme converts oleoyl-CoA into linoleoyl-CoA. In the moths Cadra cautella and Spodoptera, the enzyme converts (Z)-tetradec-9-enoic acid into (9Z,12E)-tetradeca-9,12-dienoic acid, which is reduced and acetylated to form the acetate ester pheromone [2].

References:

1. Borgeson, C.E., de Renobales, M. and Blomquist, G.J. Characterization of the Δ12 desaturase in the American cockroach, Periplaneta americana: the nature of the substrate. Biochim. Biophys. Acta 1047 (1990) 135-140. [PMID: 2248971]

2. Jurenka, R.A. Biosynthetic pathway for producing the sex pheromone component (Z,E)-9,12-tetradecadienyl acetate in moths involves a Δ12 desaturase. Cell. Mol. Life Sci. 53 (1997) 501-505. [PMID: 9230926]

3. Lomascolo, A., Dubreucq, E. and Galzy, P. Study of the Δ12-desaturase system of Lipomyces starkeyi. Lipids 31 (1996) 253-259. [PMID: 8900454]

4. Tocher, D.R., Leaver, M.J. and Hodgson, P.A. Recent advances in the biochemistry and molecular biology of fatty acyl desaturases. Prog. Lipid Res. 37 (1998) 73-117. [PMID: 9829122]

[EC 1.14.19.6 created 2008]

EC 1.14.21.7

Accepted name: biflaviolin synthase

Reaction: (1) 2 flaviolin + NADPH + H+ + O2 = 3,3'-biflaviolin + NADP+ + 2 H2O
(2) 2 flaviolin + NADPH + H+ + O2 = 3,8'-biflaviolin + NADP+ + 2 H2O

Glossary: flaviolin = 4,5,7-trihydroxynaphthalene-1,2-dione
3,3'-biflaviolin = 3,3',6,6',8,8'-hexahydroxy-2,2'-binaphthalene-1,1',4,4'-tetraone
3,8'-biflaviolin = 2,3',4,6',7,8'-hexahydroxy-1,2'-binaphthalene-1',4',5,8-tetraone

Other name(s): CYP158A2; CYP 158A2; cytochrome P450 158A2

Systematic name: flaviolin,NADPH:oxygen oxidoreductase

Comments: This cytochrome-P450 enzyme, from the soil-dwelling bacterium Streptomyces coelicolor A3(2), catalyses a phenol oxidation C-C coupling reaction, which results in the polymerization of flaviolin to form biflaviolin or triflaviolin without the incorporation of oxygen into the product [1,3]. The products are highly conjugated pigments that protect the bacterium from the deleterious effects of UV irradiation [1].

References:

1. Zhao, B., Guengerich, F.P., Bellamine, A., Lamb, D.C., Izumikawa, M., Lei, L., Podust, L.M., Sundaramoorthy, M., Kalaitzis, J.A., Reddy, L.M., Kelly, S.L., Moore, B.S., Stec, D., Voehler, M., Falck, J.R., Shimada, T. and Waterman, M.R. Binding of two flaviolin substrate molecules, oxidative coupling, and crystal structure of Streptomyces coelicolor A3(2) cytochrome P450 158A2. J. Biol. Chem. 280 (2005) 11599-11607. [PMID: 15659395]

2. Zhao, B., Guengerich, F.P., Voehler, M. and Waterman, M.R. Role of active site water molecules and substrate hydroxyl groups in oxygen activation by cytochrome P450 158A2: a new mechanism of proton transfer. J. Biol. Chem. 280 (2005) 42188-42197. [PMID: 16239228]

3. Zhao, B., Lamb, D.C., Lei, L., Kelly, S.L., Yuan, H., Hachey, D.L. and Waterman, M.R. Different binding modes of two flaviolin substrate molecules in cytochrome P450 158A1 (CYP158A1) compared to CYP158A2. Biochemistry 46 (2007) 8725-8733. [PMID: 17614370]

[EC 1.14.21.7 created 2008]

EC 2.1.3.10

Accepted name: malonyl-S-ACP:biotin-protein carboxyltransferase

Reaction: a malonyl-[acyl-carrier protein] + a biotinyl-[protein] = an acetyl-[acyl-carrier protein] + a carboxybiotinyl-[protein]

For diagram of the reaction click here

Other name(s): malonyl-S-acyl-carrier protein:biotin-protein carboxyltransferase; MadC/MadD; MadC,D; malonyl-[acyl-carrier protein]:biotinyl-[protein] carboxyltransferase

Systematic name: malonyl-[acyl-carrier protein]:biotinyl-[protein] carboxytransferase

Comments: Derived from the components MadC and MadD of the anaerobic bacterium Malonomonas rubra, this enzyme is a component of EC 4.1.1.89, biotin-dependent malonate decarboxylase. The carboxy group is transferred from malonate to the prosthetic group of the biotin protein (MadF) with retention of configuration [2]. Similar to EC 4.1.1.87, malonyl-S-ACP decarboxylase, which forms part of the biotin-independent malonate decarboxylase (EC 4.1.1.88), this enzyme also follows on from EC 2.3.1.187, acetyl-S-ACP:malonate ACP transferase, and results in the regeneration of the acetyl-[acyl-carrier protein] [3].

References:

1. Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103-115. [PMID: 9128730]

2. Micklefield, J., Harris, K.J., Gröger, S., Mocek, U., Hilbi, H., Dimroth, P. and Floss, H.G. Stereochemical course of malonate decarboxylase in Malonomonas rubra has biotin decarboxylation with retention. J. Am. Chem. Soc. 117 (1995) 1153-1154.

3. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 2.1.3.10 created 2008]

EC 2.1.3.11

Accepted name: N-succinylornithine carbamoyltransferase

Reaction: carbamoyl phosphate + N2-succinyl-L-ornithine = phosphate + N-succinyl-L-citrulline

Glossary: N-acetyl-L-citrulline = N5-acetylcarbamoyl-L-ornithine

Other name(s): succinylornithine transcarbamylase; N-succinyl-L-ornithine transcarbamylase; SOTCase

Systematic name: carbamoyl phosphate:N2-succinyl-L-ornithine carbamoyltransferase

Comments: This enzyme is specific for N-succinyl-L-ornithine and cannot use either L-ornithine (see EC 2.1.3.3, ornithine carbamoyltransferase) or N-acetyl-L-ornithine (see EC 2.1.3.9, N-acetylornithine carbamoyltransferase) as substrate. However, a single amino-acid substitution (Pro90 → Glu90) is sufficient to switch the enzyme to one that uses N-acetyl-L-ornithine as substrate. It is essential for de novo arginine biosynthesis in the obligate anaerobe Bacteroides fragilis, suggesting that this organism uses an alternative pathway for synthesizing arginine.

References:

1. Shi, D., Morizono, H., Cabrera-Luque, J., Yu, X., Roth, L., Malamy, M.H., Allewell, N.M. and Tuchman, M. Structure and catalytic mechanism of a novel N-succinyl-L-ornithine transcarbamylase in arginine biosynthesis of Bacteroides fragilis. J. Biol. Chem. 281 (2006) 20623-20631. [PMID: 16704984]

2. Shi, D., Yu, X., Cabrera-Luque, J., Chen, T.Y., Roth, L., Morizono, H., Allewell, N.M. and Tuchman, M. A single mutation in the active site swaps the substrate specificity of N-acetyl-L-ornithine transcarbamylase and N-succinyl-L-ornithine transcarbamylase. <>Protein Sci. 16 (2007) 1689-1699. [PMID: 17600144]

[EC 2.1.3.11 created 2008]

EC 2.2.1.9

Accepted name: 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase

Reaction: isochorismate + 2-oxoglutarate = 5-enolpyruvoyl-6-hydroxy-2-succinylcyclohex-3-ene-1-carboxylate + CO2

For diagram of reaction, click here.

Other name(s): SEPHCHC synthase; MenD

Systematic name: isochorismate:2-oxoglutarate 4-oxopentanoatetransferase (decarboxylating)

Comments: Requires Mg2+ for maximal activity. This enzyme is involved in the biosynthesis of vitamin K2 (menaquinone). In most anaerobes and all Gram-positive aerobes, menaquinone is the sole electron transporter in the respiratory chain and is essential for their survival. It had previously been thought that the products of the reaction were (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate (SHCHC), pyruvate and CO2 but it is now known that two separate enzymes are involved: this enzyme and EC 4.2.99.20, 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase. Under basic conditions, the product can spontaneously lose pyruvate to form SHCHC.

References:

1. Jiang, M., Cao, Y., Guo, Z.F., Chen, M., Chen, X. and Guo, Z. Menaquinone biosynthesis in Escherichia coli: identification of 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate as a novel intermediate and re-evaluation of MenD activity. Biochemistry 46 (2007) 10979-10989. [PMID: 17760421]

[EC 2.2.1.9 created 2008 (EC 2.5.1.64 created 2003, part-incorporated 2008)]

*EC 2.3.1.39

Accepted name: [acyl-carrier-protein] S-malonyltransferase

Reaction: malonyl-CoA + an [acyl-carrier protein] = CoA + a malonyl-[acyl-carrier protein]

Other name(s): [acyl carrier protein]malonyltransferase; FabD; malonyl coenzyme A-acyl carrier protein transacylase; malonyl transacylase; malonyl transferase; malonyl-CoA-acyl carrier protein transacylase; malonyl-CoA:[acyl-carrier-protein] S-malonyltransferase; malonyl-CoA:ACP transacylase; malonyl-CoA:ACP-SH transacylase; malonyl-CoA:AcpM transacylase; malonyl-CoA:acyl carrier protein transacylase; malonyl-CoA:acyl-carrier-protein transacylase; malonyl-CoA/dephospho-CoA acyltransferase; MAT; MCAT; MdcH

Systematic name: malonyl-CoA:[acyl-carrier protein] S-malonyltransferase

Comments: This enzyme, along with EC 2.3.1.38, [acyl-carrier-protein] S-acetyltransferase, is essential for the initiation of fatty-acid biosynthesis in bacteria. This enzyme also provides the malonyl groups for polyketide biosynthesis [7]. The product of the reaction, malonyl-ACP, is an elongation substrate in fatty-acid biosynthesis. In Mycobacterium tuberculosis, holo-ACP (the product of EC 2.7.8.7, holo-[acyl-carrier-protein] synthase) is the preferred substrate [5]. This enzyme also forms part of the multienzyme complexes EC 4.1.1.88 (biotin-independent malonate decarboxylase) and EC 4.1.1.89 (biotin-dependent malonate decarboxylase). Malonylation of ACP is immediately followed by decarboxylation within the malonate-decarboxylase complex to yield acetyl-ACP, the catalytically active species of the decarboxylase [12]. In the enzyme from Klebsiella pneumoniae, methylmalonyl-CoA can also act as a substrate but acetyl-CoA cannot [10] whereas the enzyme from Pseudomonas putida can use both as substrates [11]. The ACP subunit found in fatty-acid biosynthesis contains a pantetheine-4'-phosphate prosthetic group; that from malonate decarboxylase also contains pantetheine-4'-phosphate but in the form of a 2'-(5-triphosphoribosyl)-3'-dephospho-CoA prosthetic group.

Links to other databases: BRENDA, ERGO, EXPASY, GTD, KEGG, PDB, CAS registry number: 37257-17-3

References:

1. Alberts, A.W., Majerus, P.W. and Vagelos, P.R. Acetyl-CoA acyl carrier protein transacylase. Methods Enzymol. 14 (1969) 50-53.

2. Prescott, D.J. and Vagelos, P.R. Acyl carrier protein. Adv. Enzymol. Relat. Areas Mol. Biol. 36 (1972) 269-311. [PMID: 4561013]

3. Williamson, I.P. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XVII. Preparation and general properties of acetyl coenzyme A and malonyl coenzyme A-acyl carrier protein transacylases. J. Biol. Chem. 241 (1966) 2326-2332. [PMID: 5330116]

4. Joshi, V.C. and Wakil, S.J. Studies on the mechanism of fatty acid synthesis. XXVI. Purification and properties of malonyl-coenzyme A--acyl carrier protein transacylase of Escherichia coli. Arch. Biochem. Biophys. 143 (1971) 493-505. [PMID: 4934182]

5. Kremer, L., Nampoothiri, K.M., Lesjean, S., Dover, L.G., Graham, S., Betts, J., Brennan, P.J., Minnikin, D.E., Locht, C. and Besra, G.S. Biochemical characterization of acyl carrier protein (AcpM) and malonyl-CoA:AcpM transacylase (mtFabD), two major components of Mycobacterium tuberculosis fatty acid synthase II. J. Biol. Chem. 276 (2001) 27967-27974. [PMID: 11373295]

6. Keatinge-Clay, A.T., Shelat, A.A., Savage, D.F., Tsai, S.C., Miercke, L.J., O'Connell, J.D., 3rd, Khosla, C. and Stroud, R.M. Catalysis, specificity, and ACP docking site of Streptomyces coelicolor malonyl-CoA:ACP transacylase. Structure 11 (2003) 147-154. [PMID: 12575934]

7. Szafranska, A.E., Hitchman, T.S., Cox, R.J., Crosby, J. and Simpson, T.J. Kinetic and mechanistic analysis of the malonyl CoA:ACP transacylase from Streptomyces coelicolor indicates a single catalytically competent serine nucleophile at the active site. Biochemistry 41 (2002) 1421-1427. [PMID: 11814333]

8. Hoenke, S., Schmid, M. and Dimroth, P. Sequence of a gene cluster from Klebsiella pneumoniae encoding malonate decarboxylase and expression of the enzyme in Escherichia coli. Eur. J. Biochem. 246 (1997) 530-538. [PMID: 9208947]

9. Koo, J.H. and Kim, Y.S. Functional evaluation of the genes involved in malonate decarboxylation by Acinetobacter calcoaceticus. Eur. J. Biochem. 266 (1999) 683-690. [PMID: 10561613]

10. Hoenke, S. and Dimroth, P. Formation of catalytically active acetyl-S-malonate decarboxylase requires malonyl-coenzyme A:acyl carrier protein transacylase as auxiliary enzyme. Eur. J. Biochem. 259 (1999) 181-187. [PMID: 9914491]

11. Chohnan, S., Fujio, T., Takaki, T., Yonekura, M., Nishihara, H. and Takamura, Y. Malonate decarboxylase of Pseudomonas putida is composed of five subunits. FEMS Microbiol. Lett. 169 (1998) 37-43. [PMID: 9851033]

12. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 2.3.1.39 created 1972, modified 2006, modified 2008]

*EC 2.3.1.94

Accepted name: 6-deoxyerythronolide-B synthase

Reaction: propanoyl-CoA + 6 (2S)-methylmalonyl-CoA + 6 NADPH + 6 H+ = 6-deoxyerythronolide B + 7 CoA + 6 CO2 + H2O + 6 NADP+

For diagram of reaction, click here.

Other name(s): erythronolide condensing enzyme; malonyl-CoA:propionyl-CoA malonyltransferase (cyclizing); erythronolide synthase; malonyl-CoA:propanoyl-CoA malonyltransferase (cyclizing); deoxyerythronolide B synthase; 6-deoxyerythronolide B synthase; DEBS

Systematic name: propanoyl-CoA:(2S)-methylmalonyl-CoA malonyltransferase (cyclizing)

Comments: The product, 6-deoxyerythronolide B, contains a 14-membered lactone ring and is an intermediate in the biosynthesis of erythromycin antibiotics. Biosynthesis of 6-deoxyerythronolide B requires 28 active sites that are precisely arranged along three large polypeptides, denoted DEBS1, -2 and -3 [6]. The polyketide product is synthesized by the processive action of a loading didomain, six extension modules and a terminal thioesterase domain [5]. Each extension module contains a minimum of a ketosynthase (KS), an acyltransferase (AT) and an acyl-carrier protein (ACP). The KS domain both accepts the growing polyketide chain from the previous module and catalyses the subsequent decarboxylative condensation between this substrate and an ACP-bound methylmalonyl extender unit, introduce by the AT domain. This combined effort gives rise to a new polyketide intermediate that has been extended by two carbon atoms [5].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 87683-77-0

References:

1. Omura, S. and Nakagawa, A. Biosynthesis of 16-membered macrolide antibiotics. Antibiotics 4 (1981) 175-192.

2. Roberts, G. and Leadley, P.F. Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus. Biochem. Soc. Trans. 12 (1984) 642-643.

3. Pfeifer, B.A., Admiraal, S.J., Gramajo, H., Cane, D.E. and Khosla, C. Biosynthesis of complex polyketides in a metabolically engineered strain of E. coli. Science 291 (2001) 1790-1792. [PMID: 11230695]

4. Tsai, S.C., Miercke, L.J., Krucinski, J., Gokhale, R., Chen, J.C., Foster, P.G., Cane, D.E., Khosla, C. and Stroud, R.M. Crystal structure of the macrocycle-forming thioesterase domain of the erythromycin polyketide synthase: versatility from a unique substrate channel. Proc. Natl. Acad. Sci. USA 98 (2001) 14808-14813. [PMID: 11752428]

5. Khosla, C., Tang, Y., Chen, A.Y., Schnarr, N.A. and Cane, D.E. Structure and mechanism of the 6-deoxyerythronolide B synthase. Annu. Rev. Biochem. 76 (2007) 195-221. [PMID: 17328673]

[EC 2.3.1.94 created 1989, modified 2008]

EC 2.3.1.187

Accepted name: acetyl-S-ACP:malonate ACP transferase

Reaction: an acetyl-[acyl-carrier protein] + malonate = a malonyl-[acyl-carrier protein] + acetate

For diagram of the reaction click here

Other name(s): acetyl-S-ACP:malonate ACP-SH transferase; acetyl-S-acyl-carrier protein:malonate acyl-carrier-protein-transferase; MdcA; MadA; ACP transferase; malonate/acetyl-CoA transferase; malonate:ACP transferase; acetyl-S-acyl carrier protein:malonate acyl carrier protein-SH transferase

Systematic name: acetyl-[acyl-carrier-protein]:malonate S-[acyl-carrier-protein]transferase

Comments: This is the first step in the catalysis of malonate decarboxylation and involves the exchange of an acetyl thioester residue bound to the activated acyl-carrier protein (ACP) subunit of the malonate decarboxylase complex for a malonyl thioester residue [2]. This enzyme forms the α subunit of the multienzyme complexes biotin-independent malonate decarboxylase (EC 4.1.1.88) and biotin-dependent malonate decarboxylase (EC 4.1.1.89). The enzyme can also use acetyl-CoA as a substrate but more slowly [4].

References:

1. Hilbi, H. and Dimroth, P. Purification and characterization of a cytoplasmic enzyme component of the Na+-activated malonate decarboxylase system of Malonomonas rubra: acetyl-S-acyl carrier protein: malonate acyl carrier protein-SH transferase. Arch. Microbiol. 162 (1994) 48-56. [PMID: 18251085]

2. Hoenke, S., Schmid, M. and Dimroth, P. Sequence of a gene cluster from Klebsiella pneumoniae encoding malonate decarboxylase and expression of the enzyme in Escherichia coli. Eur. J. Biochem. 246 (1997) 530-538. [PMID: 9208947]

3. Koo, J.H. and Kim, Y.S. Functional evaluation of the genes involved in malonate decarboxylation by Acinetobacter calcoaceticus. Eur. J. Biochem. 266 (1999) 683-690. [PMID: 10561613]

4. Chohnan, S., Akagi, K. and Takamura, Y. Functions of malonate decarboxylase subunits from Pseudomonas putida. Biosci. Biotechnol. Biochem. 67 (2003) 214-217. [PMID: 12619701]

5. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 2.3.1.187 created 2008]

*EC 2.4.1.14

Accepted name: sucrose-phosphate synthase

Reaction: UDP-glucose + D-fructose 6-phosphate = UDP + sucrose 6F-phosphate

Other name(s): UDP-glucose—fructose-phosphate glucosyltransferase; sucrosephosphate—UDP glucosyltransferase; UDP-glucose-fructose-phosphate glucosyltransferase; SPS; uridine diphosphoglucose-fructose phosphate glucosyltransferase; sucrose 6-phosphate synthase; sucrose phosphate synthetase; sucrose phosphate-uridine diphosphate glucosyltransferase; sucrose phosphate synthase

Systematic name: UDP-glucose:D-fructose-6-phosphate 2-α-D-glucosyltransferase

Comments: Requires Mg2+ or Mn2+ for maximal activity [2]. The enzyme from Synechocystis sp. strain PCC 6803 is not specific for UDP-glucose as it can use ADP-glucose and, to a lesser extent, GDP-glucose as substrates [2]. The enzyme from rice leaves is activated by glucose 6-phosphate but that from cyanobacterial species is not [2]. While the reaction catalysed by this enzyme is reversible, the enzyme usually works in concert with EC 3.1.3.24, sucrose-phosphate phosphatase, to form sucrose, making the above reaction essentially irreversible [3]. The F in sucrose 6F-phosphate is used to indicate that the fructose residue of sucrose carries the substituent.

Links to other databases: BRENDA, ERGO, EXPASY, GTD, KEGG, CAS registry number: 9030-06-2

References:

1. Mendicino, J. Sucrose phosphate synthesis in wheat germ and green leaves. J. Biol. Chem. 235 (1960) 3347-3352. [PMID: 13769376]

2. Curatti, L., Folco, E., Desplats, P., Abratti, G., Limones, V., Herrera-Estrella, L. and Salerno, G. Sucrose-phosphate synthase from Synechocystis sp. strain PCC 6803: identification of the spsA gene and characterization of the enzyme expressed in Escherichia coli. J. Bacteriol. 180 (1998) 6776-6779. [PMID: 9852031]

3. Huber, S.C. and Huber, J.L. Role and regulation of sucrose-phosphate synthase in higher plants. Annu. Rev. Plant Physiol. Plant Mol. Biol. 47 (1996) 431-444. [PMID: 15012296]

4. Cumino, A., Curatti, L., Giarrocco, L. and Salerno, G.L. Sucrose metabolism: Anabaena sucrose-phosphate synthase and sucrose-phosphate phosphatase define minimal functional domains shuffled during evolution. FEBS Lett. 517 (2002) 19-23. [PMID: 12062401]

5. Chua, T.K., Bujnicki, J.M., Tan, T.C., Huynh, F., Patel, B.K. and Sivaraman, J. The structure of sucrose phosphate synthase from Halothermothrix orenii reveals its mechanism of action and binding mode. Plant Cell 20 (2008) 1059-1072. [PMID: 18424616]

[EC 2.4.1.14 created 1961, modified 2008]

EC 2.4.1.245

Accepted name: α,α-trehalose synthase

Reaction: ADP-glucose + D-glucose = α,α-trehalose + ADP

Other name(s): trehalose synthase; trehalose synthetase; UDP-glucose:glucose 1-glucosyltransferase; TreT; PhGT

Systematic name: ADP-glucose:D-glucose 1-α-D-glucosyltransferase

Comments: Requires Mg2+ for maximal activity [1]. The enzyme-catalysed reaction is reversible [1]. In the reverse direction to that shown above, the enzyme is specific for α,α-trehalose as substrate, as it cannot use α- or β-paranitrophenyl glucosides, maltose, sucrose, lactose or cellobiose [1]. While the enzyme from the hyperthermophilic archaeon Pyrococcus horikoshii can use ADP-, UDP- and GDP-glucose to the same extent [2], that from Thermococcus litoralis has a marked preference for ADP [1].

References:

1. Qu, Q., Lee, S.J. and Boos, W. TreT, a novel trehalose glycosyltransferring synthase of the hyperthermophilic archaeon Thermococcus litoralis. J. Biol. Chem. 279 (2004) 47890-47897. [PMID: 15364950]

2. Ryu, S.I., Park, C.S., Cha, J., Woo, E.J. and Lee, S.B. A novel trehalose-synthesizing glycosyltransferase from Pyrococcus horikoshii: molecular cloning and characterization. Biochem. Biophys. Res. Commun. 329 (2005) 429-436. [PMID: 15737605]

[EC 2.4.1.245 created 2008]

[EC 2.5.1.64 Transferred entry: 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase. The reaction that was attributed to this enzyme is now known to be catalysed by two separate enzymes: EC 2.2.1.9 EC 2.2.1.9 (2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase) and EC 4.2.99.20 (2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase). (EC 2.5.1.64 created 2003, deleted 2008)]

EC 2.5.1.72

Accepted name: quinolinate synthase

Reaction: glycerone phosphate + iminosuccinate = pyridine-2,3-dicarboxylate + 2 H2O + phosphate

Glossary: quinolinate = pyridine-2,3-dicarboxylate
glycerone phosphate = dihydroxyacetone phosphate = 3-hydroxy-2-oxopropyl phosphate

Other name(s): NadA; QS; quinolinate synthetase

Systematic name: glycerone phosphate:iminosuccinate alkyltransferase (cyclizing)

Comments: An iron-sulfur protein that requires a [4Fe-4S] cluster for activity [1]. Quinolinate synthase catalyses the second step in the de novo biosynthesis of NAD+ from aspartate in some bacteria, with EC 1.4.3.16 (L-aspartate oxidase) catalysing the first step and EC 2.4.2.19 [nicotinate-nucleotide diphosphorylase (carboxylating)] the third step. In Escherichia coli, two of the residues that are involved in the [4Fe-4S] cluster binding appear to undergo reversible disulfide-bond formation that regulates the activity of the enzyme [5].

References:

1. Ollagnier-de Choudens, S., Loiseau, L., Sanakis, Y., Barras, F. and Fontecave, M. Quinolinate synthetase, an iron-sulfur enzyme in NAD biosynthesis. FEBS Lett. 579 (2005) 3737-3743. [PMID: 15967443]

2. Katoh, A., Uenohara, K., Akita, M. and Hashimoto, T. Early steps in the biosynthesis of NAD in Arabidopsis start with aspartate and occur in the plastid. Plant Physiol. 141 (2006) 851-857. [PMID: 16698895]

3. Sakuraba, H., Tsuge, H., Yoneda, K., Katunuma, N. and Ohshima, T. Crystal structure of the NAD biosynthetic enzyme quinolinate synthase. J. Biol. Chem. 280 (2005) 26645-26648. [PMID: 15937336]

4. Rousset, C., Fontecave, M. and Ollagnier de Choudens, S. The [4Fe-4S] cluster of quinolinate synthase from Escherichia coli: Investigation of cluster ligands. FEBS Lett. 582 (2008) 2937-2944. [PMID: 18674537]

5. Saunders, A.H. and Booker, S.J. Regulation of the activity of Escherichia coli quinolinate synthase by reversible disulfide-bond formation. Biochemistry 47 (2008) 8467-8469. [PMID: 18651751]

[EC 2.5.1.72 created 2008]

*EC 2.7.7.61

Accepted name: citrate lyase holo-[acyl-carrier protein] synthase

Reaction: 2'-(5-triphosphoribosyl)-3'-dephospho-CoA + citrate lyase apo-[acyl-carrier protein] = citrate lyase holo-[acyl-carrier protein] + diphosphate

For diagram of holo-citrate-lyase biosynthesis, click here

Other name(s): 2'-(5"-phosphoribosyl)-3'-dephospho-CoA transferase; 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA:apo-citrate lyase; CitX; holo-ACP synthase (ambiguous); 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA:apo-citrate lyase adenylyltransferase; 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA:apo-citrate lyase 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA transferase; 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA:apo-citrate-lyase adenylyltransferase; holo-citrate lyase synthase (incorrect)

Systematic name: 2'-(5-triphosphoribosyl)-3'-dephospho-CoA:apo-citrate-lyase 2'-(5-phosphoribosyl)-3'-dephospho-CoA-transferase

Comments: The γ-subunit of EC 4.1.3.6, citrate (pro-3S) lyase, serves as an acyl-carrier protein (ACP) and contains the prosthetic group 2'-(5-triphosphoribosyl)-3'-dephospho-CoA [1,3]. Synthesis and attachment of the prosthetic group requires the concerted action of this enzyme and EC 2.7.8.25, triphosphoribosyl-dephospho-CoA synthase [1]. In the enzyme from Escherichia coli, the prosthetic group is attached to serine-14 of the ACP via a phosphodiester bond.

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 312492-44-7

References:

1. Schneider, K., Dimroth, P. and Bott, M. Biosynthesis of the prosthetic group of citrate lyase. Biochemistry 39 (2000) 9438-9450. [PMID: 10924139]

2. Schneider, K., Dimroth, P. and Bott, M. Identification of triphosphoribosyl-dephospho-CoA as precursor of the citrate lyase prosthetic group. FEBS Lett. 483 (2000) 165-168. [PMID: 11042274]

3. Schneider, K., Kästner, C.N., Meyer, M., Wessel, M., Dimroth, P. and Bott, M. Identification of a gene cluster in Klebsiella pneumoniae which includes citX, a gene required for biosynthesis of the citrate lyase prosthetic group. J. Bacteriol. 184 (2002) 2439-2446. [PMID: 11948157]

[EC 2.7.7.61 created 2002, modified 2008]

EC 2.7.7.66

Accepted name: malonate decarboxylase holo-[acyl-carrier protein] synthase

Reaction: 2'-(5-triphosphoribosyl)-3'-dephospho-CoA + malonate decarboxylase apo-[acyl-carrier protein] = malonate decarboxylase holo-[acyl-carrier protein] + diphosphate

For diagram click here

Other name(s): holo ACP synthase (ambiguous); 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA:apo ACP 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA transferase; MdcG; 2'-(5"-triphosphoribosyl)-3'-dephospho-CoA:apo-malonate-decarboxylase adenylyltransferase; holo-malonate-decarboxylase synthase (incorrect)

Systematic name: 2'-(5-triphosphoribosyl)-3'-dephospho-CoA:apo-malonate-decarboxylase 2'-(5-phosphoribosyl)-3'-dephospho-CoA-transferase

Comments: The δ subunit of malonate decarboxylase serves as an an acyl-carrier protein (ACP) and contains the prosthetic group 2'-(5-triphosphoribosyl)-3'-dephospho-CoA. Two reactions are involved in the production of the holo-ACP form of this enzyme. The first reaction is catalysed by EC 2.7.8.25, triphosphoribosyl-dephospho-CoA synthase. The resulting prosthetic group is then attached to the ACP subunit via a phosphodiester linkage to a serine residue, thus forming the holo form of the enzyme, in a manner analogous to that of EC 2.7.7.61, citrate lyase holo-[acyl-carrier protein] synthase.

References:

1. Hoenke, S., Wild, M.R. and Dimroth, P. Biosynthesis of triphosphoribosyl-dephospho-coenzyme A, the precursor of the prosthetic group of malonate decarboxylase. Biochemistry 39 (2000) 13223-13232. [PMID: 11052675]

2. Hoenke, S., Schmid, M. and Dimroth, P. Identification of the active site of phosphoribosyl-dephospho-coenzyme A transferase and relationship of the enzyme to an ancient class of nucleotidyltransferases. Biochemistry 39 (2000) 13233-13240. [PMID: 11052676]

[EC 2.7.7.66 created 2008]

*EC 2.7.8.25

Accepted name: triphosphoribosyl-dephospho-CoA synthase

Reaction: ATP + 3-dephospho-CoA = 2'-(5-triphosphoribosyl)-3'-dephospho-CoA + adenine

For diagram of holo-citrate-lyase biosynthesis, click here

Other name(s): 2'-(5"-triphosphoribosyl)-3-dephospho-CoA synthase; ATP:dephospho-CoA 5-triphosphoribosyl transferase; CitG; ATP:dephospho-CoA 5'-triphosphoribosyl transferase; MdcB; ATP:3-dephospho-CoA 5";-triphosphoribosyltransferase

Systematic name: ATP:3'-dephospho-CoA 5-triphosphoribosyltransferase

Comments: ATP cannot be replaced by GTP, CTP, UTP, ADP or AMP. The reaction involves the formation of a new α (1"→2') glycosidic bond between the two ribosyl moieties, with concomitant displacement of the adenine moiety of ATP [1,4]. The 2'-(5-triphosphoribosyl)-3'-dephospho-CoA produced can be transferred by EC 2.7.7.61, citrate lyase holo-[acyl-carrier protein] synthase, to the apo-acyl-carrier protein subunit (γ-subunit) of EC 4.1.3.6, citrate (pro-3S) lyase, thus converting it from an apo-enzyme into a holo-enzyme [1,3]. Alternatively, it can be transferred to the apo-ACP subunit of malonate decarboxylase by the action of EC 2.7.7.66, malonate decarboxylase holo-[acyl-carrier protein] synthase [4].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 313345-38-9

References:

1. Schneider, K., Dimroth, P. and Bott, M. Biosynthesis of the prosthetic group of citrate lyase. Biochemistry 39 (2000) 9438-9450. [PMID: 10924139]

2. Schneider, K., Dimroth, P. and Bott, M. Identification of triphosphoribosyl-dephospho-CoA as precursor of the citrate lyase prosthetic group. FEBS Lett. 483 (2000) 165-168. [PMID: 11042274]

3. Schneider, K., Kästner, C.N., Meyer, M., Wessel, M., Dimroth, P. and Bott, M. Identification of a gene cluster in Klebsiella pneumoniae which includes citX, a gene required for biosynthesis of the citrate lyase prosthetic group. J. Bacteriol. 184 (2002) 2439-2446. [PMID: 11948157]

4. Hoenke, S., Wild, M.R. and Dimroth, P. Biosynthesis of triphosphoribosyl-dephospho-coenzyme A, the precursor of the prosthetic group of malonate decarboxylase. Biochemistry 39 (2000) 13223-13232. [PMID: 11052675]

[EC 2.7.8.25 created 2002, modified 2008]

EC 3.1.1.83

Accepted name: monoterpene ε-lactone hydrolase

Reaction: (1) isoprop(en)ylmethyloxepan-2-one + H2O = 6-hydroxyisoprop(en)ylmethylhexanoate (general reaction)
(2) 4-isopropenyl-7-methyloxepan-2-one + H2O = 6-hydroxy-3-isopropenylheptanoate
(3) 7-isopropyl-4-methyloxepan-2-one + H2O = 6-hydroxy-3,7-dimethyloctanoate

Other name(s): MLH

Systematic name: isoprop(en)ylmethyloxepan-2-one lactonohydrolase

Comments: The enzyme catalyses the ring opening of ε-lactones which are formed during degradation of dihydrocarveol by the Gram-positive bacterium Rhodococcus erythropolis DCL14. The enzyme also acts on ethyl caproate, indicating that it is an esterase with a preference for lactones (internal cyclic esters). The enzyme is not stereoselective.

References:

1. van der Vlugt-Bergmans , C.J. and van der Werf , M.J. Genetic and biochemical characterization of a novel monoterpene ε-lactone hydrolase from Rhodococcus erythropolis DCL14. Appl. Environ. Microbiol. 67 (2001) 733-741. [PMID: 11157238]

[EC 3.1.1.83 created 2008]

*EC 3.1.3.24

Accepted name: sucrose-phosphate phosphatase

Reaction: sucrose 6F-phosphate + H2O = sucrose + phosphate

Other name(s): sucrose 6-phosphate hydrolase; sucrose-phosphate hydrolase; sucrose-phosphate phosphohydrolase; sucrose-6-phosphatase (incorrect); sucrose-phosphatase (incorrect); sucrose-6-phosphate phosphatase; SPP

Systematic name: sucrose-6F-phosphate phosphohydrolase

Comments: Requires Mg2+ for maximal activity [2]. This is the final step in the sucrose-biosynthesis pathway. The enzyme is highly specific for sucrose 6-phosphate, with fructose 6-phosphate unable to act as a substrate [2]. Belongs in the haloacid dehydrogenase (HAD) superfamily. The F of sucrose 6F-phosphate is used to indicate that the fructose residue of sucrose carries the substituent.

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 9059-33-0

References:

1. Hawker, J.S. and Hatch, M.D. A specific sucrose phosphatase from plant tissues. Biochem. J. 99 (1966) 102-107. [PMID: 4290548]

2. Lunn, J.E., Ashton, A.R., Hatch, M.D. and Heldt, H.W. Purification, molecular cloning, and sequence analysis of sucrose-6F-phosphate phosphohydrolase from plants. Proc. Natl. Acad. Sci. USA 97 (2000) 12914-12919. [PMID: 11050182]

3. Lunn, J.E. and MacRae, E. New complexities in the synthesis of sucrose. Curr. Opin. Plant Biol. 6 (2003) 208-214. [PMID: 12753969]

4. Fieulaine, S., Lunn, J.E., Borel, F. and Ferrer, J.L. The structure of a cyanobacterial sucrose-phosphatase reveals the sugar tongs that release free sucrose in the cell. Plant Cell 17 (2005) 2049-2058. [PMID: 15937230]

[EC 3.1.3.24 created 1972, modified 2008]

EC 3.1.3.78

Accepted name: phosphatidylinositol-4,5-bisphosphate 4-phosphatase

Reaction: 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1-phosphatidyl-1D-myo-inositol 5-phosphate + phosphate

Other name(s): phosphatidylinositol-4,5-bisphosphate 4-phosphatase I; phosphatidylinositol-4,5-bisphosphate 4-phosphatase II; type I PtdIns-4,5-P2 4-Ptase; type II PtdIns-4,5-P2 4-Ptase; IpgD; PtdIns-4,5-P2 4-phosphatase type I; PtdIns-4,5-P2 4-phosphatase type II; type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase; type 1 4-phosphatase

Systematic name: 1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 4-phosphohydrolase

Comments: Two pathways exist in mammalian cells to degrade 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [PtdIns(4,5)P2] [2]. One is catalysed by this enzyme and the other by EC 3.1.3.36, phosphoinositide 5-phosphatase, where the product is PtdIns4P. The enzyme from human is specific for PtdIns(4,5)P2 as substrate, as it cannot use PtdIns(3,4,5)P3, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns5P, PtdIns4P or PtdIns3P [2]. In humans, the enzyme is localized to late endosomal/lysosomal membranes [2]. It can control nuclear levels of PtdIns(5)P and thereby control p53-dependent apoptosis [3].

References:

1. Niebuhr, K., Giuriato, S., Pedron, T., Philpott, D.J., Gaits, F., Sable, J., Sheetz, M.P., Parsot, C., Sansonetti, P.J. and Payrastre, B. Conversion of PtdIns(4,5)P2 into PtdIns(5)P by the S. flexneri effector IpgD reorganizes host cell morphology. EMBO J. 21 (2002) 5069-5078. [PMID: 12356723]

2. Ungewickell, A., Hugge, C., Kisseleva, M., Chang, S.C., Zou, J., Feng, Y., Galyov, E.E., Wilson, M. and Majerus, P.W. The identification and characterization of two phosphatidylinositol-4,5-bisphosphate 4-phosphatases. Proc. Natl. Acad. Sci. USA 102 (2005) 18854-18859. [PMID: 16365287]

3. Zou, J., Marjanovic, J., Kisseleva, M.V., Wilson, M. and Majerus, P.W. Type I phosphatidylinositol-4,5-bisphosphate 4-phosphatase regulates stress-induced apoptosis. Proc. Natl. Acad. Sci. USA 104 (2007) 16834-16839. [PMID: 17940011]

4. Mason, D., Mallo, G.V., Terebiznik, M.R., Payrastre, B., Finlay, B.B., Brumell, J.H., Rameh, L. and Grinstein, S. Alteration of epithelial structure and function associated with PtdIns(4,5)P2 degradation by a bacterial phosphatase. J. Gen. Physiol. 129 (2007) 267-283. [PMID: 17389247]

[EC 3.1.3.78 created 2008]

EC 3.1.4.53

Accepted name: 3',5'-cyclic-AMP phosphodiesterase

Reaction: adenosine 3',5'-cyclic phosphate + H2O = adenosine 5'-phosphate

Other name(s): cAMP-specific phosphodiesterase; cAMP-specific PDE; PDE1; PDE2A; PDE2B; PDE4; PDE7; PDE8; PDEB1; PDEB2

Systematic name: 3',5'-cyclic-AMP 5'-nucleotidohydrolase

Comments: Requires Mg2+ or Mn2+ for activity [2]. This enzyme is a class I phosphodiesterase that is specific for 3',5'-cAMP and does not hydrolyse other nucleoside 3',5'-cyclic phosphates such as cGMP (c.f. EC 3.1.4.17, 3"-cyclic-nucleotide phosphodiesterase and EC 3.1.4.35, 3',5'-cyclic-GMP phosphodiesterase). It is involved in modulation of the levels of cAMP, which is a mediator in the processes of cell transformation and proliferation [3].

References:

1. Alonso, G.D., Schoijet, A.C., Torres, H.N. and Flawiá, M.M. TcPDE4, a novel membrane-associated cAMP-specific phosphodiesterase from Trypanosoma cruzi. Mol. Biochem. Parasitol. 145 (2006) 40-49. [PMID: 16225937]

2. Bader, S., Kortholt, A., Snippe, H. and Van Haastert, P.J. DdPDE4, a novel cAMP-specific phosphodiesterase at the surface of Dictyostelium cells. J. Biol. Chem. 281 (2006) 20018-20026. [PMID: 16644729]

3. Rascón, A., Soderling, S.H., Schaefer, J.B. and Beavo, J.A. Cloning and characterization of a cAMP-specific phosphodiesterase (TbPDE2B) from Trypanosoma brucei. Proc. Natl. Acad. Sci. USA 99 (2002) 4714-4719. [PMID: 11930017]

4. Johner, A., Kunz, S., Linder, M., Shakur, Y. and Seebeck, T. Cyclic nucleotide specific phosphodiesterases of Leishmania major. BMC Microbiol. 6:25 (2006). [PMID: 16522215]

5. Lugnier, C., Keravis, T., Le Bec, A., Pauvert, O., Proteau, S. and Rousseau, E. Characterization of cyclic nucleotide phosphodiesterase isoforms associated to isolated cardiac nuclei. Biochim. Biophys. Acta 1472 (1999) 431-446. [PMID: 10564757]

[EC 3.1.4.53 created 2008]

EC 3.1.7.4

Accepted name: sclareol cyclase

Reaction: geranylgeranyl diphosphate + 2 H2O = sclareol + diphosphate

Glossary: sclareol = labd-14-ene-8,13-diol

Other name(s): geranylgeranyl pyrophosphate:sclareol cyclase; geranylgeranyl pyrophosphate-sclareol cyclase; GGPP:sclareol cyclase

Systematic name: geranylgeranyl-diphosphate diphosphohydrolase (sclareol-forming)

Comments: Requires Mg2+ or Mn2+ for activity [3]. Sclareol, a labdane diterpene, is a plant secondary metabolite that exhibits potent antibacterial activity as well as fungal-growth-regulating and plant-growth-inhibiting properties. It also exhibits cytotoxic activity against human leukaemic cell lines by inducing apoptosis [2].

References:

1. Banthorpe, D.V., Brown, J.T. and Morris, G.S. Partial purification of farnesyl pyrophosphate:drimenol cyclase and geranylgerany pyrophosphate:sclareol cyclase, using cell culture as a source of material. Phytochemistry 31 (1992) 3391-3395.

2. Dimas, K., Hatziantoniou, S., Tseleni, S., Khan, H., Georgopoulos, A., Alevizopoulos, K., Wyche, J.H., Pantazis, P. and Demetzos, C. Sclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient mice. Apoptosis 12 (2007) 685-694. [PMID: 17260186]

3. Guo, Z. and Wagner, G.J. Biosynthesis of labdenediol and sclareol in cell-free extracts from trichomes of Nicotiana glutinosa. Planta 197 (1995) 627-632.

[EC 3.1.7.4 created 2008]

EC 3.1.26.12

Accepted name: ribonuclease E

Reaction: Endonucleolytic cleavage of single-stranded RNA in A- and U-rich regions

Other name(s): endoribonuclease E; RNase E; Rne protein

Comments: RNase E is a bacterial ribonuclease that plays a role in the processing of ribosomal RNA (9S to 5S rRNA), the chemical degradation of bulk cellular RNA, the decay of specific regulatory, messenger and structural RNAs and the control of plasmid DNA replication [1]. The enzyme binds to monophosphorylated 5' ends of substrates but exhibits sequential cleavages in the 3' to 5' direction [1]. 2'-O-Methyl nucleotide substitutions at RNase E binding sites do not prevent binding but do prevent cleavage of non-modified target sequences 5' to that locus [1]. In Escherichia coli, the enzyme is found in the RNA degradosome. The C-terminal half of the protein contains binding sites for the three other major degradosomal components, the DEAD-box RNA helicase Rh1B, enolase (EC 4.1.1.11) and polynucleotide phosphorylase (EC 2.7.7.8).

References:

1. Feng, Y., Vickers, T.A. and Cohen, S.N. The catalytic domain of RNase E shows inherent 3' to 5' directionality in cleavage site selection. Proc. Natl. Acad. Sci. USA 99 (2002) 14746-14751. [PMID: 12417756]

2. Ehretsmann, C.P., Carpousis, A.J. and Krisch, H.M. Specificity of Escherichia coli endoribonuclease RNase E: in vivo and in vitro analysis of mutants in a bacteriophage T4 mRNA processing site. Genes Dev. 6 (1992) 149-159. [PMID: 1730408]

3. Cormack, R.S., Genereaux, J.L. and Mackie, G.A. RNase E activity is conferred by a single polypeptide: overexpression, purification, and properties of the ams/rne/hmp1 gene product. Proc. Natl. Acad. Sci. USA 90 (1993) 9006-9010. [PMID: 8415644]

4. Vanzo, N.F., Li, Y.S., Py, B., Blum, E., Higgins, C.F., Raynal, L.C., Krisch, H.M. and Carpousis, A.J. Ribonuclease E organizes the protein interactions in the Escherichia coli RNA degradosome. Genes Dev. 12 (1998) 2770-2781. [PMID: 9732274]

5. Steege, D.A. Emerging features of mRNA decay in bacteria. RNA 6 (2000) 1079-1090. [PMID: 10943888]

6. Callaghan, A.J., Grossmann, J.G., Redko, Y.U., Ilag, L.L., Moncrieffe, M.C., Symmons, M.F., Robinson, C.V., McDowall, K.J. and Luisi, B.F. Quaternary structure and catalytic activity of the Escherichia coli ribonuclease E amino-terminal catalytic domain. Biochemistry 42 (2003) 13848-13855. [PMID: 14636052]

[EC 3.1.26.12 created 2008]

*EC 3.2.1.97

Accepted name: glycopeptide α-N-acetylgalactosaminidase

Reaction: Hydrolysis of O-glycosidic linkages of sugar chains between α-N-acetyl-D-galactosamine and serine or threonine residues in glycoproteins

Other name(s): endo-α-N-acetylgalactosaminidase; endo-α-acetylgalactosaminidase; endo-α-N-acetyl-D-galactosaminidase; mucinaminylserine mucinaminidase; D-galactosyl-3-(N-acetyl-α-D-galactosaminyl)-L-serine mucinaminohydrolase; endo-α-GalNAc-ase

Systematic name: D-galactosyl-N-acetyl-α-D-galactosamine D-galactosyl-N-acetyl-galactosaminohydrolase

Comments: The inability of the enzyme to hydrolyse substrates such as NeuAc→Gal→GalNAc-Ser/Thr, GalNAc→Gal→GalNAc→Ser/Thr, GalNAc→(Fuc)→GalNAc-Ser/Thr and NeuAc→GalNAc-Ser/Thr, together with the fact that galactose is an inhibitor of the enzyme, suggests that a non-reducing galactose terminus is necessary for recognition of the substrate by the enzyme [3]. The enzyme cannot release Gal→GalNAc from asialo (GM1) ganglioside, which suggests that the β-N-acetylgalactosaminyl linkage is not recognized by the enzyme [3].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number: 59793-96-3

References:

1. Bhavanandan, V.P., Umemoto, J. and Davidson, E.A. Characterization of an endo-α-N-acetyl galactosaminidase from Diplococcus pneumoniae. Biochem. Biophys. Res. Commun. 70 (1976) 738-745. [PMID: 7253]

2. Endo, Y. and Kibata, A. Partial purification and characterization of an endo-α-N-acetylgalactosaminidase from the culture of medium of Diplococcus pneumoniae. J. Biochem. (Tokyo) 80 (1976) 1-8. [PMID: 9374]

3. Umemoto, J., Bhavanandan, V.P. and Davidson, E.A. Purification and properties of an endo-α-N-acetyl-D-galactosaminidase from Diplococcus pneumoniae. J. Biol. Chem. 252 (1977) 8609-8614. [PMID: 21877]

[EC 3.2.1.97 created 1978 (EC 3.2.1.110 created 1984, incorporated 2008), modified 2008]

[EC 3.2.1.110 Deleted entry: mucinaminylserine mucinaminidase. The enzyme is identical to EC 3.2.1.97, glycopeptide α-N-acetylgalactosaminidase (EC 3.2.1.110 created 1984, deleted 2008)]

EC 3.2.2.26

Accepted name: futalosine hydrolase

Reaction: futalosine + H2O = dehypoxanthine futalosine + hypoxanthine

Glossary: futalosine = 3-(3-((3S,4R)-3,4-dihydroxy-5-(6-oxo-3H-purin-9(6H)-yl)tetrahydrofuran-2-yl)propanoyl)benzoate
dehypoxanthine futalosine = 3-(3-((3S,4R)-3,4,5-trihydroxytetrahydrofuran-2-yl)propanoyl)benzoate

Other name(s): futalosine nucleosidase; MqnB

Systematic name: futalosine ribohydrolase

Comments: This enzyme, which is specific for futalosine, catalyses the second step of a novel menaquinone biosynthetic pathway that is found in some prokaryotes.

References:

1. Hiratsuka, T., Furihata, K., Ishikawa, J., Yamashita, H., Itoh, N., Seto, H. and Dairi, T. An alternative menaquinone biosynthetic pathway operating in microorganisms. Science 321 (2008) 1670-1673. [PMID: 18801996]

[EC 3.2.2.26 created 2008]

EC 3.4.11.24

Accepted name: aminopeptidase S

Reaction: Release of an N-terminal amino acid with a preference for large hydrophobic amino-terminus residues

Other name(s): Mername-AA022 peptidase; SGAP; aminopeptidase (Streptomyces griseus); Streptomyces griseus aminopeptidase; S. griseus AP; double-zinc aminopeptidase

Comments: Aminopeptidases are associated with many biological functions, including protein maturation, protein degradation, cell-cycle control and hormone-level regulation [3,4]. This enzyme contains two zinc molecules in its active site and is activated by Ca2+ [4]. In the presence of Ca2+, the best substrates are Leu-Phe, Leu-Ser, Leu-pNA (aminoacyl-p-nitroanilide), Phe-Phe-Phe and Phe-Phe [3]. Peptides with proline in the P1' position are not substrates [3]. Belongs in peptidase family M28.

References:

1. Spungin, A. and Blumberg, S. Streptomyces griseus aminopeptidase is a calcium-activated zinc metalloprotein. Purification and properties of the enzyme. Eur. J. Biochem. 183 (1989) 471-477. [PMID: 2503378]

2. Ben-Meir, D., Spungin, A., Ashkenazi, R. and Blumberg, S. Specificity of Streptomyces griseus aminopeptidase and modulation of activity by divalent metal ion binding and substitution. Eur. J. Biochem. 212 (1993) 107-112. [PMID: 8444149]

3. Arima, J., Uesugi, Y., Iwabuchi, M. and Hatanaka, T. Study on peptide hydrolysis by aminopeptidases from Streptomyces griseus, Streptomyces septatus and Aeromonas proteolytica. Appl. Microbiol. Biotechnol. 70 (2006) 541-547. [PMID: 16080009]

4. Fundoiano-Hershcovitz, Y., Rabinovitch, L., Langut, Y., Reiland, V., Shoham, G. and Shoham, Y. Identification of the catalytic residues in the double-zinc aminopeptidase from Streptomyces griseus. FEBS Lett. 571 (2004) 192-196. [PMID: 15280041]

5. Gilboa, R., Greenblatt, H.M., Perach, M., Spungin-Bialik, A., Lessel, U., Wohlfahrt, G., Schomburg, D., Blumberg, S. and Shoham, G. Interactions of Streptomyces griseus aminopeptidase with a methionine product analogue: a structural study at 1.53 Å resolution. Acta Crystallogr. D Biol. Crystallogr. 56 (2000) 551-558. [PMID: 10771423]

[EC 3.4.11.24 created 2008]

*EC 3.5.1.77

Accepted name: N-carbamoyl-D-amino-acid hydrolase

Reaction: an N-carbamoyl-D-amino acid + H2O = a D-amino acid + NH3 + CO2

Other name(s): D-N-carbamoylase; N-carbamoylase (ambiguous); N-carbamoyl-D-amino acid hydrolase

Systematic name: N-carbamoyl-D-amino-acid amidohydrolase

Comments: This enzyme, along with EC 3.5.1.87 (N-carbamoyl-L-amino-acid hydrolase), EC 5.1.99.5 (hydantoin racemase) and hydantoinase, forms part of the reaction cascade known as the "hydantoinase process", which allows the total conversion of D,L-5-monosubstituted hydantoins into optically pure D- or L-amino acids [2]. It has strict stereospecificity for N-carbamoyl-D-amino acids and does not act upon the corresponding L-amino acids or on the N-formyl amino acids, N-carbamoyl-sarcosine, -citrulline, -allantoin and -ureidopropanoate, which are substrates for other amidohydrolases.

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 71768-08-6

References:

1. Ogawa, J., Shimizu, S., Yamada, H. N-Carbamoyl-D-amino acid amidohydrolase from Comamonas sp. E222c; purification and characterization. Eur. J. Biochem. 212 (1993) 685-691. [PMID: 8462543]

2. Altenbuchner, J., Siemann-Herzberg, M. and Syldatk, C. Hydantoinases and related enzymes as biocatalysts for the synthesis of unnatural chiral amino acids. Curr. Opin. Biotechnol. 12 (2001) 559-563. [PMID: 11849938]

[EC 3.5.1.77 created 1999, modified 2008]

*EC 3.5.1.87

Accepted name: N-carbamoyl-L-amino-acid hydrolase

Reaction: an N-carbamoyl-L-2-amino acid (a 2-ureido carboxylate) + H2O = an L-2-amino acid + NH3 + CO2

Other name(s): N-carbamyl L-amino acid amidohydrolase; N-carbamoyl-L-amino acid amidohydrolase; L-N-carbamoylase; N-carbamoylase (ambiguous)

Systematic name: N-carbamoyl-L-amino-acid amidohydrolase

Comments: This enzyme, along with EC 3.5.1.77 (N-carbamoyl-D-amino-acid hydrolase), EC 5.1.99.5 (hydantoin racemase) and hydantoinase, forms part of the reaction cascade known as the "hydantoinase process", which allows the total conversion of D,L-5-monosubstituted hydantoins into optically pure D- or L-amino acids [3]. The enzyme from Alcaligenes xylosoxidans has broad specificity for carbamoyl-L-amino acids, although it is inactive on the carbamoyl derivatives of glutamate, aspartate, arginine, tyrosine or tryptophan. The enzyme from Sinorhizobium meliloti requires a divalent cation for activity and can hydrolyse N-carbamoyl-L-tryptophan as well as N-carbamoyl L-amino acids with aliphatic substituents [2]. The enzyme is inactive on derivatives of D-amino acids. In addition to N-carbamoyl L-amino acids, the enzyme can also hydrolyse formyl and acetyl derivatives to varying degrees [1,2].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG

References:

1. Ogawa, J., Miyake, H. and Shimizu, S. Purification and characterization of N-carbamoyl-L-amino acid amidohydrolase with broad substrate specificity from Alcaligenes xylosoxidans. Appl. Microbiol. Biotechnol. 43 (1995) 1039-1043. [PMID: 8590654]

2. Martínez-Rodríguez, S., Clemente-Jiménez, J.M., Rodríguez-Vico, F. and Las Heras-Vázquez, F.J. Molecular cloning and biochemical characterization of L-N-carbamoylase from Sinorhizobium meliloti CECT4114. J. Mol. Microbiol. Biotechnol. 9 (2005) 16-25. [PMID: 16254442]

3. Altenbuchner, J., Siemann-Herzberg, M. and Syldatk, C. Hydantoinases and related enzymes as biocatalysts for the synthesis of unnatural chiral amino acids. Curr. Opin. Biotechnol. 12 (2001) 559-563. [PMID: 11849938]

[EC 3.5.1.87 created 2001, modified 2008]

EC 3.6.1.53

Accepted name: Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase

Reaction: (1) CDP-choline + H2O = CMP + phosphocholine
(2) ADP-ribose + H2O = AMP + D-ribose 5-phosphate

Other name(s): Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase; ADPRibase-Mn

Systematic name: CDP-choline phosphohydrolase

Comments: Requires Mn2+, which cannot be replaced by Mg2+, for activity. ADP-ribose, CDP-choline, CDP-ethanolamine and ADP are substrates for this enzyme but ADP-glucose, UDP-glucose, CDP-glucose, CDP, CMP and AMP are not hydrolysed [2]. In rat, the enzyme is found predominantly in thymus and spleen.

References:

1. Canales, J., Pinto, R.M., Costas, M.J., Hernández, M.T., Miró, A., Bernet, D., Fernández, A. and Cameselle, J.C. Rat liver nucleoside diphosphosugar or diphosphoalcohol pyrophosphatases different from nucleotide pyrophosphatase or phosphodiesterase I: substrate specificities of Mg2+-and/or Mn2+-dependent hydrolases acting on ADP-ribose. Biochim. Biophys. Acta 1246 (1995) 167-177. [PMID: 7819284]

2. Canales, J., Fernández, A., Ribeiro, J.M., Cabezas, A., Rodrigues, J.R., Cameselle, J.C. and Costas, M.J. Mn2+-dependent ADP-ribose/CDP-alcohol pyrophosphatase: a novel metallophosphoesterase family preferentially expressed in rodent immune cells. Biochem. J. 413 (2008) 103-113. [PMID: 18352857]

[EC 3.6.1.53 created 2008]

EC 4.1.1.87

Accepted name: malonyl-S-ACP decarboxylase

Reaction: a malonyl-[acyl-carrier protein] + H+ = an acetyl-[acyl-carrier protein] + CO2

For diagram of the reaction click here

Other name(s): malonyl-S-acyl-carrier protein decarboxylase; MdcD/MdcE; MdcD,E

Systematic name: malonyl-[acyl-carrier-protein] carboxy-lyase

Comments: This enzyme comprises the β and γ subunits of EC 4.1.1.88 (biotin-independent malonate decarboxylase) but is not present in EC 4.1.1.89 (biotin-dependent malonate decarboxylase). It follows on from EC 2.3.1.187, acetyl-S-ACP:malonate ACP transferase, and results in the regeneration of the acetylated form of the acyl-carrier-protein subunit of malonate decarboxylase [5]. The carboxy group is lost with retention of configuration [3].

References:

1. Schmid, M., Berg, M., Hilbi, H. and Dimroth, P. Malonate decarboxylase of Klebsiella pneumoniae catalyses the turnover of acetyl and malonyl thioester residues on a coenzyme-A-like prosthetic group. Eur. J. Biochem. 237 (1996) 221-228. [PMID: 8620876]

2. Koo, J.H. and Kim, Y.S. Functional evaluation of the genes involved in malonate decarboxylation by Acinetobacter calcoaceticus<. Eur. J. Biochem. 266 (1999) 683-690. [PMID: 10561613]

3. Handa, S., Koo, J.H., Kim, Y.S. and Floss, H.G. Stereochemical course of biotin-independent malonate decarboxylase catalysis. Arch. Biochem. Biophys. 370 (1999) 93-96. [PMID: 10496981]

4. Chohnan, S., Akagi, K. and Takamura, Y. Functions of malonate decarboxylase subunits from Pseudomonas putida. Biosci. Biotechnol. Biochem. 67 (2003) 214-217. [PMID: 12619701]

5. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 4.1.1.87 created 2008]

EC 4.1.1.88

Accepted name: biotin-independent malonate decarboxylase

Reaction: malonate + H+ = acetate + CO2

For diagram of the reactions of the multienzyme complex click here

Other name(s): malonate decarboxylase (without biotin); malonate decarboxylase (ambiguous); MDC

Systematic name: malonate carboxy-lyase (biotin-independent)

Comments: Two types of malonate decarboxylase are currently known, both of which form multienzyme complexes. This enzyme is a cytosolic protein that is biotin-independent. The other type is a biotin-dependent, Na+-translocating enzyme that includes both soluble and membrane-bound components (cf. EC 4.1.1.89, biotin-dependent malonate decarboxylase). As free malonate is chemically rather inert, it has to be activated prior to decarboxylation. In both enzymes, this is achieved by exchanging malonate with an acetyl group bound to an acyl-carrier protiein (ACP), to form malonyl-ACP and acetate, with subsequent decarboxylation regenerating the acetyl-ACP. The ACP subunit of both enzymes differs from that found in fatty-acid biosynthesis by having phosphopantethine attached to a serine side-chain as 2'-(5-triphosphoribosyl)-3'-dephospho-CoA rather than as phosphopantetheine 4'-phosphate. The individual enzymes involved in carrying out the reaction of this enzyme complex are EC 2.3.1.187 (acetyl-S-ACP:malonate ACP transferase), EC 2.3.1.39 ([acyl-carrier-protein] S-malonyltransferase) and EC 4.1.1.87 (malonyl-S-ACP decarboxylase). The carboxy group is lost with retention of configuration [6].

References:

1. Schmid, M., Berg, M., Hilbi, H. and Dimroth, P. Malonate decarboxylase of Klebsiella pneumoniae catalyses the turnover of acetyl and malonyl thioester residues on a coenzyme-A-like prosthetic group. Eur. J. Biochem. 237 (1996) 221-228. [PMID: 8620876]

2. Byun, H.S. and Kim, Y.S. Subunit organization of bacterial malonate decarboxylases: the smallest δ subunit as an acyl-carrier protein. J. Biochem. Mol. Biol. 30 (1997) 132-137.

3. Hoenke, S., Schmid, M. and Dimroth, P. Sequence of a gene cluster from Klebsiella pneumoniae encoding malonate decarboxylase and expression of the enzyme in Escherichia coli. Eur. J. Biochem. 246 (1997) 530-538. [PMID: 9208947]

4. Chohnan, S., Fujio, T., Takaki, T., Yonekura, M., Nishihara, H. and Takamura, Y. Malonate decarboxylase of Pseudomonas putida is composed of five subunits. FEMS Microbiol. Lett. 169 (1998) 37-43. [PMID: 9851033]

5. Hoenke, S., Schmid, M. and Dimroth, P. Identification of the active site of phosphoribosyl-dephospho-coenzyme A transferase and relationship of the enzyme to an ancient class of nucleotidyltransferases. Biochemistry 39 (2000) 13233-13240. [PMID: 11052676]

6. Handa, S., Koo, J.H., Kim, Y.S. and Floss, H.G. Stereochemical course of biotin-independent malonate decarboxylase catalysis. Arch. Biochem. Biophys. 370 (1999) 93-96. [PMID: 10496981]

7. Koo, J.H. and Kim, Y.S. Functional evaluation of the genes involved in malonate decarboxylation by Acinetobacter calcoaceticus. Eur. J. Biochem. 266 (1999) 683-690. [PMID: 10561613]

8. Kim, Y.S. Malonate metabolism: biochemistry, molecular biology, physiology, and industrial application. J. Biochem. Mol. Biol. 35 (2002) 443-451. [PMID: 12359084]

9. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 4.1.1.88 created 2008]

EC 4.1.1.89

Accepted name: biotin-dependent malonate decarboxylase

Reaction: malonate + H+ = acetate + CO2

For diagram of the reactions involved in the multienzyme complex click here

Other name(s): malonate decarboxylase (with biotin); malonate decarboxylase (ambiguous)

Systematic name: malonate carboxy-lyase (biotin-dependent)

Comments: Two types of malonate decarboxylase are currently known, both of which form multienzyme complexes. The enzyme described here is a biotin-dependent, Na+-translocating enzyme that includes both soluble and membrane-bound components [6]. The other type is a biotin-independent cytosolic protein (cf. EC 4.1.1.88, biotin-independent malonate decarboxylase). As free malonate is chemically rather inert, it has to be activated prior to decarboxylation. Both enzymes achieve this by exchanging malonate with an acetyl group bound to an acyl-carrier protiein (ACP), to form malonyl-ACP and acetate, with subsequent decarboxylation regenerating the acetyl-bound form of the enzyme. The ACP subunit of both enzymes differs from that found in fatty-acid biosynthesis by having phosphopantethine attached to a serine side-chain as 2'-(5-triphosphoribosyl)-3'-dephospho-CoA rather than as phosphopantetheine 4'-phosphate. In the anaerobic bacterium Malonomonas rubra, the components of the multienzyme complex/enzymes involved in carrying out the reactions of this enzyme are as follows: MadA (EC 2.3.1.187, acetyl-S-ACP:malonate ACP transferase), MadB (EC 4.3.99.2, carboxybiotin decarboxylase), MadC/MadD (EC 2.1.3.10, malonyl-S-ACP:biotin-protein carboxyltransferase) and MadH (EC 6.2.1.35, ACP-SH:acetate ligase). Two other components that are involved are MadE, the acyl-carrier protein and MadF, the biotin protein. The carboxy group is lost with retention of configuration [5].

References:

1. Hilbi, H., Dehning, I., Schink, B. and Dimroth, P. Malonate decarboxylase of Malonomonas rubra, a novel type of biotin-containing acetyl enzyme. Eur. J. Biochem. 207 (1992) 117-123. [PMID: 1628643]

2. Hilbi, H. and Dimroth, P. Purification and characterization of a cytoplasmic enzyme component of the Na+-activated malonate decarboxylase system of Malonomonas rubra: acetyl-S-acyl carrier protein: malonate acyl carrier protein-SH transferase. Arch. Microbiol. 162 (1994) 48-56. [PMID: 18251085]

3. Berg, M., Hilbi, H. and Dimroth, P. The acyl carrier protein of malonate decarboxylase of Malonomonas rubra contains 2'-(5"-phosphoribosyl)-3'-dephosphocoenzyme A as a prosthetic group. Biochemistry 35 (1996) 4689-4696. [PMID: 8664258]

4. Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103-115. [PMID: 9128730]

5. Micklefield, J., Harris, K.J., Gröger, S., Mocek, U., Hilbi, H., Dimroth, P. and Floss, H.G. Stereochemical course of malonate decarboxylase in Malonomonas rubra has biotin decarboxylation with retention. J. Am. Chem. Soc. 117 (1995) 1153-1154.

6. Kim, Y.S. Malonate metabolism: biochemistry, molecular biology, physiology, and industrial application. J. Biochem. Mol. Biol. 35 (2002) 443-451. [PMID: 12359084]

7. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 4.1.1.89 created 2008]

EC 4.1.2.43

Accepted name: 3-hexulose-6-phosphate synthase

Reaction: D-arabino-hex-3-ulose 6-phosphate = D-ribulose 5-phosphate + formaldehyde

For diagram of reaction, click here

Other name(s): D-arabino-3-hexulose 6-phosphate formaldehyde-lyase; 3-hexulosephosphate synthase; 3-hexulose phosphate synthase; HPS

Systematic name: D-arabino-3-hexulose-6-phosphate formaldehyde-lyase (D-ribulose-5-phosphate-forming)

Comments: Requires Mg2+ or Mn2+ for maximal activity [1]. The enzyme is specific for formaldehyde and D-ribulose 5-phosphate as substrates. Ribose 5-phosphate, xylulose 5-phosphate, allulose 6-phosphate and fructose 6-phosphate cannot act as substrate. This enzyme, along with EC 5.3.1.27, 6-phospho-3-hexuloisomerase, plays a key role in the ribulose-monophosphate cycle of formaldehyde fixation, which is present in many microorganisms that are capable of utilizing C1-compounds [1]. The hyperthermophilic and anaerobic archaeon Pyrococcus horikoshii OT3 constitutively produces a bifunctional enzyme that sequentially catalyses the reactions of this enzyme and EC 5.3.1.27, 6-phospho-3-hexuloisomerase [6]. This enzyme is a member of the orotidine 5'-monophosphate decarboxylase (OMPDC) suprafamily [5].

References:

1. Ferenci, T., Strøm, T. and Quayle, J.R. Purification and properties of 3-hexulose phosphate synthase and phospho-3-hexuloisomerase from Methylococcus capsulatus. Biochem. J. 144 (1974) 477-486. [PMID: 4219834]

2. Kato, N., Ohashi, H., Tani, Y. and Ogata, K. 3-Hexulosephosphate synthase from Methylomonas aminofaciens 77a. Purification, properties and kinetics. Biochim. Biophys. Acta 523 (1978) 236-244. [PMID: 564713]

3. Yanase, H., Ikeyama, K., Mitsui, R., Ra, S., Kita, K., Sakai, Y. and Kato, N. Cloning and sequence analysis of the gene encoding 3-hexulose-6-phosphate synthase from the methylotrophic bacterium, Methylomonas aminofaciens 77a, and its expression in Escherichia coli. FEMS Microbiol. Lett. 135 (1996) 201-205. [PMID: 8595859]

4. Yurimoto, H., Kato, N. and Sakai, Y. Assimilation, dissimilation, and detoxification of formaldehyde, a central metabolic intermediate of methylotrophic metabolism. Chem. Rec. 5 (2005) 367-375. [PMID: 16278835]

5. Kato, N., Yurimoto, H. and Thauer, R.K. The physiological role of the ribulose monophosphate pathway in bacteria and archaea. Biosci. Biotechnol. Biochem. 70 (2006) 10-21. [PMID: 16428816]

6. Orita, I., Yurimoto, H., Hirai, R., Kawarabayasi, Y., Sakai, Y. and Kato, N. The archaeon Pyrococcus horikoshii possesses a bifunctional enzyme for formaldehyde fixation via the ribulose monophosphate pathway. J. Bacteriol. 187 (2005) 3636-3642. [PMID: 15901685]

7. Kato, N., Miyamoto, N., Shimao, M. and Sakazawa, C. 3-Hexulose phosphate pynthase from a new facultative methylotroph, Mycobacterium gastri MB19. Agric. Biol. Chem. 52 (1988) 265-2661.

[EC 4.1.2.43 created 2008]

*EC 4.2.1.92

Accepted name: hydroperoxide dehydratase

Reaction: (9Z,11E,15Z)-(13S)-hydroperoxyoctadeca-9,11,15-trienoate = (9Z,15Z)-(13S)-12,13-epoxyoctadeca-9,11,15-trienoate + H2O

Glossary: 13-hydroperoxylinolenoate = (9Z,11E,15Z)-(13S)-hydroperoxyoctadeca-9,11,15-trienoate

Other name(s): hydroperoxide isomerase; linoleate hydroperoxide isomerase; linoleic acid hydroperoxide isomerase; HPI; (9Z,11E,14Z)-(13S)-hydroperoxyoctadeca-9,11,14-trienoate 12,13-hydro-lyase; (9Z,11E,14Z)-(13S)-hydroperoxyoctadeca-9,11,14-trienoate 12,13-hydro-lyase [(9Z)-(13S)-12,13-epoxyoctadeca-9,11-dienoate-forming]; allene oxide synthase; AOS

Systematic name: (9Z,11E,15Z)-(13S)-hydroperoxyoctadeca-9,11,15-trienoate 12,13-hydro-lyase [(9Z,15Z)-(13S)-12,13-epoxyoctadeca-9,11,15-trienoate-forming]

Comments: Acts on a number of unsaturated fatty-acid hydroperoxides, forming the corresponding allene oxides. The product of the above reaction is unstable and is acted upon by EC 5.3.99.6, allene-oxide cyclase, to form the cyclopentenone derivative (15Z)-12-oxophyto-10,15-dienoate (OPDA), which is the first cyclic and biologically active metabolite in the jasmonate biosynthesis pathway [3]. The enzyme from many plants belongs to the CYP-74 family of P450 monooxygenases [4].

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, CAS registry number:

References:

1. Esselman, W.J. and Clagett, C.O. Products of linoleic hydroperoxide-decomposing enzyme of alfalfa seed. J. Lipid Res. 15 (1974) 173-178. [PMID: 4208994]

2. Hamberg, M. Mechanism of corn hydroperoxide isomerase - detection of 12,13(S)-oxido-9(Z),11-octadecadienoic acid. Biochim. Biophys. Acta 920 (1987) 76-84.

3. Hamberg, M. Biosynthesis of 12-oxo-10,15(Z)-phytodienoic acid: identification of an allene oxide cyclase. Biochem. Biophys. Res. Commun. 156 (1988) 543-550. [PMID: 3178850]

4. Laudert, D., Pfannschmidt, U., Lottspeich, F., Holländer-Czytko, H. and Weiler, E.W. Cloning, molecular and functional characterization of Arabidopsis thaliana allene oxide synthase (CYP 74), the first enzyme of the octadecanoid pathway to jasmonates. Plant Mol. Biol. 31 (1996) 323-335. [PMID: 8756596]

[EC 4.2.1.92 created 1992, modified 2008]

EC 4.2.3.36

Accepted name: terpentetriene synthase

Reaction: terpentedienyl diphosphate = terpentetriene + diphosphate

Other name(s): Cyc2

Systematic name: terpentedienyl-diphosphate diphosphate-lyase (terpentetriene-forming)

Comments: Requires Mg2+ for maximal activity but can use Mn2+, Fe2+ or Co2+ to a lesser extent [2]. Following on from EC 5.5.1.15, terpentedienyl-diphosphate synthase, this enzyme completes the transformation of geranylgeranyl diphosphate (GGDP) into terpentetriene, which is a precursor of the diterpenoid antibiotic terpentecin. Farnesyl diphosphate can also act as a substrate.

References:

1. Dairi, T., Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K. and Seto, H. Eubacterial diterpene cyclase genes essential for production of the isoprenoid antibiotic terpentecin. J. Bacteriol. 183 (2001) 6085-6094. [PMID: 11567009]

2. Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K., Seto, H. and Dairi, T. Functional analysis of eubacterial diterpene cyclases responsible for biosynthesis of a diterpene antibiotic, terpentecin. J. Biol. Chem. 277 (2002) 37098-37104. [PMID: 12138123]

3. Eguchi, T., Dekishima, Y., Hamano, Y., Dairi, T., Seto, H. and Kakinuma, K. A new approach for the investigation of isoprenoid biosynthesis featuring pathway switching, deuterium hyperlabeling, and 1H NMR spectroscopy. The reaction mechanism of a novel streptomyces diterpene cyclase. J. Org. Chem. 68 (2003) 5433-5438. [PMID: 12839434]

[EC 4.2.3.36 created 2008]

EC 4.2.3.37

Accepted name: epi-isozizaene synthase

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

For diagram of reaction click here

Glossary: for epi-isozizaene click here.

Other name(s): SCO5222 protein

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-epi-isozizaene-forming]

Comments: Requires Mg2+ for activity. The displacement of the diphosphate group of farnesyl diphosphate occurs with retention of configuration [1]. In the soil-dwelling bacterium Streptomyces coelicolor A3(2), the product of this reaction is used by EC 1.14.13.106, epi-isozizaene 5-monooxygenase, to produce the sesquiterpene antibiotic albaflavenone [2].

References:

1. Lin, X., Hopson, R. and Cane, D.E. Genome mining in Streptomyces coelicolor: molecular cloning and characterization of a new sesquiterpene synthase. J. Am. Chem. Soc. 128 (2006) 6022-6023. [PMID: 16669656]

2. Zhao, B., Lin, X., Lei, L., Lamb, D.C., Kelly, S.L., Waterman, M.R. and Cane, D.E. Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor A3(2). J. Biol. Chem. 283 (2008) 8183-8189. [PMID: 18234666]

[EC 4.2.3.37 created 2008]

EC 4.2.99.20

Accepted name: 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase

Reaction: 5-enolpyruvoyl-6-hydroxy-2-succinylcyclohex-3-ene-1-carboxylate = (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate + pyruvate

Other name(s): 2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylic acid synthase; 6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate synthase; SHCHC synthase; MenH; YfbB

Systematic name: 5-enolpyruvoyl-6-hydroxy-2-succinylcyclohex-3-ene-1-carboxylate pyruvate-lyase [(1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate-forming)

Comments: This enzyme is involved in the biosynthesis of vitamin K2 (menaquinone). In most anaerobes and all Gram-positive aerobes, menaquinone is the sole electron transporter in the respiratory chain and is essential for their survival. It had previously been thought that the reactions carried out by this enzyme and EC 2.2.1.9, 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase, were carried out by a single enzyme but this has since been disproved [2].

References:

1. Jiang, M., Chen, X., Guo, Z.F., Cao, Y., Chen, M. and Guo, Z. Identification and characterization of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase in the menaquinone biosynthesis of Escherichia coli. Biochemistry 47 (2008) 3426-3434. [PMID: 18284213]

2. Jiang, M., Cao, Y., Guo, Z.F., Chen, M., Chen, X. and Guo, Z. Menaquinone biosynthesis in Escherichia coli: identification of 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate as a novel intermediate and re-evaluation of MenD activity. Biochemistry 46 (2007) 10979-10989. [PMID: 17760421]

[EC 4.2.99.20 created 2008 (EC 2.5.1.64 created 2003, part-incorporated 2008)]

EC 4.3.99.2

Accepted name: carboxybiotin decarboxylase

Reaction: a carboxybiotinyl-[protein] + n Na+in + H+out = CO2 + a biotinyl-[protein] + n Na+out (n = 1—2)

For diagram of the reaction click here

Other name(s): MadB; carboxybiotin protein decarboxylase

Systematic name: carboxybiotinyl-[protein] carboxy-lyase

Comments: The integral membrane protein MadB from the anaerobic bacterium Malonomonas rubra is a component of the multienzyme complex EC 4.1.1.89, biotin-dependent malonate decarboxylase. The free energy of the decarboxylation reaction is used to pump Na+ out of the cell. The enzyme is a member of the Na+-translocating decarboxylase family, other members of which include EC 4.1.1.3 (oxaloacetate decarboxylase) and EC 4.1.1.41 (methylmalonyl-CoA decarboxylase) [2].

References:

1. Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103-115. [PMID: 9128730]

2. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 4.3.99.2 created 2008]

EC 5.1.99.5

Accepted name: hydantoin racemase

Reaction: D-5-monosubstituted hydantoin = L-5-monosubstituted hydantoin

Other name(s): 5'-monosubstituted-hydantoin racemase; HyuA; HyuE

Systematic name: D-5-monosubstituted-hydantoin racemase

Comments: This enzyme, along with N-carbamoylase (EC 3.5.1.77 and EC 3.5.1.87) and hydantoinase, forms part of the reaction cascade known as the "hydantoinase process", which allows the total conversion of D,L-5-monosubstituted hydantoins into optically pure D- or L-amino acids [7]. The enzyme from Pseudomonas sp. (HyuE) has a preference for hydantoins with aliphatic substituents, e.g. D- and L-5-(2-methylthioethyl)hydantoin, whereas that from Arthrobacter aurescens shows highest activity with arylalkyl substituents, especially 5-benzylhydantoin, at the 5-position [2]. In the enzyme from Sinorhizobium meliloti, Cys76 is responsible for recognition and proton retrieval of D-isomers, while Cys181 is responsible for L-isomer recognition and racemization [6].

References:

1. Watabe, K., Ishikawa, T., Mukohara, Y. and Nakamura, H. Purification and characterization of the hydantoin racemase of Pseudomonas sp. strain NS671 expressed in Escherichia coli. J. Bacteriol. 174 (1992) 7989-7995. [PMID: 1459947]

2. Wiese, A., Pietzsch, M., Syldatk, C., Mattes, R. and Altenbuchner, J. Hydantoin racemase from Arthrobacter aurescens DSM 3747: heterologous expression, purification and characterization. J. Biotechnol. 80 (2000) 217-230. [PMID: 10949312]

3. Martínez-Rodríguez, S., Las Heras-Vázquez, F.J., Mingorance-Cazorla, L., Clemente-Jiménez, J.M. and Rodríguez-Vico, F. Molecular cloning, purification, and biochemical characterization of hydantoin racemase from the legume symbiont Sinorhizobium meliloti CECT 4114. Appl. Environ. Microbiol. 70 (2004) 625-630. [PMID: 14711700]

4. Martínez-Rodríguez, S., Las Heras-Vázquez, F.J., Clemente-Jiménez, J.M. and Rodríguez-Vico, F. Biochemical characterization of a novel hydantoin racemase from Agrobacterium tumefaciens C58. Biochimie 86 (2004) 77-81. [PMID: 15016445]

5. Suzuki, S., Onishi, N. and Yokozeki, K. Purification and characterization of hydantoin racemase from Microbacterium liquefaciens AJ 3912. Biosci. Biotechnol. Biochem. 69 (2005) 530-536. [PMID: 15784981]

6. Martínez-Rodríguez, S., Andújar-Sánchez, M., Neira, J.L., Clemente-Jiménez, J.M., Jara-Pérez, V., Rodríguez-Vico, F. and Las Heras-Vázquez, F.J. Site-directed mutagenesis indicates an important role of cysteines 76 and 181 in the catalysis of hydantoin racemase from Sinorhizobium meliloti. Protein Sci. 15 (2006) 2729-2738. [PMID: 17132860]

7. Altenbuchner, J., Siemann-Herzberg, M. and Syldatk, C. Hydantoinases and related enzymes as biocatalysts for the synthesis of unnatural chiral amino acids. Curr. Opin. Biotechnol. 12 (2001) 559-563. [PMID: 11849938]

[EC 5.1.99.5 created 2008]

EC 5.3.1.27

Accepted name: 6-phospho-3-hexuloisomerase

Reaction: D-arabino-hex-3-ulose 6-phosphate = D-fructose 6-phosphate

For diagram of reaction, click here

Other name(s): 3-hexulose-6-phosphate isomerase; phospho-3-hexuloisomerase; PHI; 6-phospho-3-hexulose isomerase; YckF

Systematic name: D-arabino-3-hexulose-6-phosphate isomerase

Comments: This enzyme, along with EC 4.1.2.43, 3-hexulose-6-phosphate synthase, plays a key role in the ribulose-monophosphate cycle of formaldehyde fixation, which is present in many microorganisms that are capable of utilizing C1-compounds [1]. The hyperthermophilic and anaerobic archaeon Pyrococcus horikoshii OT3 constitutively produces a bifunctional enzyme that sequentially catalyses the reactions of EC 4.1.2.43 (3-hexulose-6-phosphate synthase) and this enzyme [4].

References:

1. Ferenci, T., Strøm, T. and Quayle, J.R. Purification and properties of 3-hexulose phosphate synthase and phospho-3-hexuloisomerase from Methylococcus capsulatus. Biochem. J. 144 (1974) 477-486. [PMID: 4219834]

2. Yurimoto, H., Kato, N. and Sakai, Y. Assimilation, dissimilation, and detoxification of formaldehyde, a central metabolic intermediate of methylotrophic metabolism. Chem. Rec. 5 (2005) 367-375. [PMID: 16278835]

3. Kato, N., Yurimoto, H. and Thauer, R.K. The physiological role of the ribulose monophosphate pathway in bacteria and archaea. Biosci. Biotechnol. Biochem. 70 (2006) 10-21. [PMID: 16428816]

4. Orita, I., Yurimoto, H., Hirai, R., Kawarabayasi, Y., Sakai, Y. and Kato, N. The archaeon Pyrococcus horikoshii possesses a bifunctional enzyme for formaldehyde fixation via the ribulose monophosphate pathway. J. Bacteriol. 187 (2005) 3636-3642. [PMID: 15901685]

5. Martinez-Cruz, L.A., Dreyer, M.K., Boisvert, D.C., Yokota, H., Martinez-Chantar, M.L., Kim, R. and Kim, S.H. Crystal structure of MJ1247 protein from M. jannaschii at 2.0 Å resolution infers a molecular function of 3-hexulose-6-phosphate isomerase. Structure 10 (2002) 195-204. [PMID: 11839305]

6. Taylor, E.J., Charnock, S.J., Colby, J., Davies, G.J. and Black, G.W. Cloning, purification and characterization of the 6-phospho-3-hexulose isomerase YckF from Bacillus subtilis. Acta Crystallogr. D Biol. Crystallogr. 57 (2001) 1138-1140. [PMID: 11468398]

[EC 5.3.1.27 created 2008]

EC 5.5.1.15

Accepted name: terpentedienyl-diphosphate synthase

Reaction: geranylgeranyl diphosphate = terpentedienyl diphosphate

Other name(s): terpentedienol diphosphate synthase; Cyc1; clerodadienyl diphosphate synthase

Systematic name: terpentedienyl-diphosphate lyase (decyclizing)

Comments: Requires Mg2+. Contains a DXDD motif, which is a characteristic of diterpene cylases whose reactions are initiated by protonation at the 14,15-double bond of geranylgeranyl diphosphate (GGDP) [2]. The triggering proton is lost at the end of the cyclization reaction [3]. The product of the reaction, terpentedienyl diphosphate, is the substrate for EC 4.2.3.36, terpentetriene synthase and is a precursor of the diterpenoid antibiotic terpentecin.

References:

1. Dairi, T., Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K. and Seto, H. Eubacterial diterpene cyclase genes essential for production of the isoprenoid antibiotic terpentecin. J. Bacteriol. 183 (2001) 6085-6094. [PMID: 11567009]

2. Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K., Seto, H. and Dairi, T. Functional analysis of eubacterial diterpene cyclases responsible for biosynthesis of a diterpene antibiotic, terpentecin. J. Biol. Chem. 277 (2002) 37098-37104. [PMID: 12138123]

3. Eguchi, T., Dekishima, Y., Hamano, Y., Dairi, T., Seto, H. and Kakinuma, K. A new approach for the investigation of isoprenoid biosynthesis featuring pathway switching, deuterium hyperlabeling, and 1H NMR spectroscopy. The reaction mechanism of a novel streptomyces diterpene cyclase. J. Org. Chem. 68 (2003) 5433-5438. [PMID: 12839434]

[EC 5.5.1.15 created 2008]

EC 5.5.1.16

Accepted name: halimadienyl-diphosphate synthase

Reaction: geranylgeranyl diphosphate = halima-5(6),13-dien-15-yl diphosphate

Other name(s): Rv3377c; halimadienyl diphosphate synthase; tuberculosinol diphosphate synthase

Systematic name: halima-5(6),13-dien-15-yl-diphosphate lyase (cyclizing)

Comments: Requires Mg2+ for activity. This enzyme is found in pathogenic prokaryotes such as Mycobacterium tuberculosis but not in non-pathogens such as Mycobacterium smegmatis so may play a role in pathogenicity. The product of the reaction is subsequently dephosphorylated yielding tuberculosinol [halima-5(6),13-dien-15-ol].

References:

1. Nakano, C., Okamura, T., Sato, T., Dairi, T. and Hoshino, T. Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for producing the halimane skeleton. Chem. Commun. (Camb.) (2005) 1016-1018. [PMID: 15719101]

[EC 5.5.1.16 created 2008]

EC 6.2.1.35

Accepted name: ACP-SH:acetate ligase

Reaction: ATP + acetate + an [acyl-carrier protein] = AMP + diphosphate + an acetyl-[acyl-carrier protein]

For diagram of the reaction click here

Other name(s): HS-acyl-carrier protein:acetate ligase; [acyl-carrier protein]:acetate ligase; MadH

Systematic name: acetate:[acyl-carrier-protein] ligase (AMP-forming)

Comments: This enzyme, from the anaerobic bacterium Malonomonas rubra, is a component of the multienzyme complex EC 4.1.1.89, biotin-dependent malonate decarboxylase. The enzyme uses the energy from hydrolysis of ATP to convert the thiol group of the acyl-carrier-protein-bound 2'-(5-phosphoribosyl)-3'-dephospho-CoA prosthetic group into its acetyl thioester [2].

References:

1. Hilbi, H., Dehning, I., Schink, B. and Dimroth, P. Malonate decarboxylase of Malonomonas rubra, a novel type of biotin-containing acetyl enzyme. Eur. J. Biochem. 207 (1992) 117-123. [PMID: 1628643]

2. Berg, M., Hilbi, H. and Dimroth, P. The acyl carrier protein of malonate decarboxylase of Malonomonas rubra contains 2'-(5"-phosphoribosyl)-3'-dephosphocoenzyme A as a prosthetic group. Biochemistry 35 (1996) 4689-4696. [PMID: 8664258]

3. Berg, M., Hilbi, H. and Dimroth, P. Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function. Eur. J. Biochem. 245 (1997) 103-115. [PMID: 9128730]

4. Dimroth, P. and Hilbi, H. Enzymic and genetic basis for bacterial growth on malonate. Mol. Microbiol. 25 (1997) 3-10. [PMID: 11902724]

[EC 6.2.1.35 created 2008]


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