Proposed Changes to the Enzyme List

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

Contents

For diagram of reaction click here.

Other name(s): F-dehydrogenase; FdeH

Systematic name: 5-exo-hydroxycamphor:NADP⁺ oxidoreductase

Comments: Contains Zn²⁺. Isolated from Pseudomonas putida, and involved in degradation of (+)-camphor.

References:

1. Rheinwald, J.G., Chakrabarty, A.M. and Gunsalus, I.C. A transmissible plasmid controlling camphor oxidation in Pseudomonas putida. Proc. Natl. Acad. Sci. USA 70 (1973) 885-889. [PMID: 4351810]

2. Koga, H., Yamaguchi, E., Matsunaga, K., Aramaki, H. and Horiuchi, T. Cloning and nucleotide sequences of NADH-putidaredoxin reductase gene (camA) and putidaredoxin gene (camB) involved in cytochrome P-450_cam hydroxylase of Pseudomonas putida. J. Biochem. 106 (1989) 831-836. [PMID: 2613690]

3. Aramaki, H., Koga, H., Sagara, Y., Hosoi, M. and Horiuchi, T. Complete nucleotide sequence of the 5-exo-hydroxycamphor dehydrogenase gene on the CAM plasmid of Pseudomonas putida (ATCC 17453). Biochim. Biophys. Acta 1174 (1993) 91-94. [PMID: 8334169]

[EC 1.3.1.52 Transferred entry: 2-methyl-branched-chain-enoyl-CoA reductase. Now EC 1.3.8.5, 2-methyl-branched-chain-enoyl-CoA reductase (EC 1.3.1.52 created 1992, deleted 2012)]

EC 1.3.1.92

Accepted name: artemisinic aldehyde Δ¹¹⁽¹³⁾-reductase

Reaction: (11R)-dihydroartemisinic aldehyde + NADP⁺ = artemisinic aldehyde + NADPH + H⁺

For diagram of reaction click here.

Other name(s): Dbr2

Systematic name: artemisinic aldehyde:NADP⁺ oxidoreductase

Comments: Cloned from Artemisia annua. In addition to the reduction of artemisinic aldehyde it is also able to a lesser extent to reduce artemisinic alcohol and artemisinic acid. Part of the biosyntheis of artemisinin.

References:

1. Bertea, C.M., Freije, J.R., van der Woude, H., Verstappen, F.W., Perk, L., Marquez, V., De Kraker, J.W., Posthumus, M.A., Jansen, B.J., de Groot, A., Franssen, M.C. and Bouwmeester, H.J. Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua. Planta Med. 71 (2005) 40-47. [PMID: 15678372]

2. Zhang, Y., Teoh, K.H., Reed, D.W., Maes, L., Goossens, A., Olson, D.J., Ross, A.R. and Covello, P.S. The molecular cloning of artemisinic aldehyde Δ¹¹⁽¹³⁾ reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua. J. Biol. Chem. 283 (2008) 21501-21508. [PMID: 18495659]

*EC 1.3.8.1

Accepted name: short-chain acyl-CoA dehydrogenase

Reaction: a short-chain acyl-CoA + electron-transfer flavoprotein = a short-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein

Glossary: a short-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains less than 6 carbon atoms.

Other name(s): butyryl-CoA dehydrogenase; butanoyl-CoA dehydrogenase; butyryl dehydrogenase; unsaturated acyl-CoA reductase; ethylene reductase; enoyl-coenzyme A reductase; unsaturated acyl coenzyme A reductase; butyryl coenzyme A dehydrogenase; short-chain acyl CoA dehydrogenase; short-chain acyl-coenzyme A dehydrogenase; 3-hydroxyacyl CoA reductase; butanoyl-CoA:(acceptor) 2,3-oxidoreductase; ACADS (gene name).

Systematic name: short-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase

Comments: Contains FAD as prosthetic group. One of several enzymes that catalyse the first step in fatty acids β-oxidation. The enzyme catalyses the oxidation of saturated short-chain acyl-CoA thioesters to give a trans 2,3-unsaturated product by removal of the two pro-R-hydrogen atoms. The enzyme from beef liver accepts substrates with acyl chain lengths of 3 to 8 carbon atoms. The highest activity was reported with either butanoyl-CoA [2] or pentanoyl-CoA [4]. The enzyme from rat has only 10% activity with hexanoyl-CoA (compared to butanoyl-CoA) and no activity with octanoyl-CoA [6]. cf. EC 1.3.8.7, medium-chain acyl-CoA dehydrogenase, EC 1.3.8.8, long-chain acyl-CoA dehydrogenase, and EC 1.3.8.9, very-long-chain acyl-CoA dehydrogenase.

Links to other databases: BRENDA, EXPASY, GTD, KEGG, PDB, UM-BBD, CAS registry number: 9027-88-7

References:

1. Mahler, H.R. Studies on the fatty acid oxidizing system of animal tissue. IV. The prosthetic group of butyryl coenzyme A dehydrogenase. J. Biol. Chem. 206 (1954) 13-26. [PMID: 13130522]

2. Green, D.E., Mii, S., Mahler, H.R. and Bock, R.M. Studies on the fatty acid oxidizing system of animal tissue. III. Butyryl coenzyme A dehydrogenase. J. Biol. Chem. 206 (1954) 1-12. [PMID: 13130521]

3. Beinert, H. Acyl coenzyme A dehydrogenase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 447-466.

4. Shaw, L. and Engel, P.C. The purification and properties of ox liver short-chain acyl-CoA dehydrogenase. Biochem. J. 218 (1984) 511-520. [PMID: 6712627]

5. Thorpe, C. and Kim, J.J. Structure and mechanism of action of the acyl-CoA dehydrogenases. FASEB J. 9 (1995) 718-725. [PMID: 7601336]

6. Ikeda, Y., Ikeda, K.O. and Tanaka, K. Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme. J. Biol. Chem. 260 (1985) 1311-1325. [PMID: 3968063]

7. McMahon, B., Gallagher, M.E. and Mayhew, S.G. The protein coded by the PP2216 gene of Pseudomonas putida KT2440 is an acyl-CoA dehydrogenase that oxidises only short-chain aliphatic substrates. FEMS Microbiol. Lett. 250 (2005) 121-127. [PMID: 16024185]

EC 1.3.8.5

Accepted name: 2-methyl-branched-chain-enoyl-CoA reductase

Reaction: 2-methylbutanoyl-CoA + electron-transfer flavoprotein = (E)-2-methylbut-2-enoyl-CoA + reduced electron-transfer flavoprotein + H⁺

Systematic name: 2-methyl-branched-chain-acyl-CoA:electron-transfer flavoprotein 2-oxidoreductase

Comments: A flavoprotein (FAD) from Ascaris suum. The enzyme functions in shuttling reducing power from the electron-transport chain to 2-methyl branched-chain enoyl CoA

References:

1. Komuniecki, R., Fekete, S. and Thissen-Parra, J. Purification and characterization of the 2-methyl branched-chain acyl-CoA dehydrogenase, an enzyme involved in NADH-dependent enoyl-CoA reduction in anaerobic mitochondria of the nematode, Ascaris suum. J. Biol. Chem. 260 (1985) 4770-4777. [PMID: 3988734]

2. Komuniecki, R., McCrury, J., Thissen, J. and Rubin, N. Electron-transfer flavoprotein from anaerobic Ascaris suum mitochondria and its role in NADH-dependent 2-methyl branched-chain enoyl-CoA reduction. Biochim. Biophys. Acta 975 (1989) 127-131. [PMID: 2736251]

EC 1.3.8.6

Accepted name: glutaryl-CoA dehydrogenase

Reaction: glutaryl-CoA + electron-transfer flavoprotein = (E)-but-2-enoyl-CoA + CO₂ + reduced electron-transfer flavoprotein (overall reaction)
(1a) glutaryl-CoA + electron-transfer flavoprotein = (2E)-4-carboxybut-2-enoyl-CoA + reduced electron-transfer flavoprotein
(1b) (2E)-4-carboxybut-2-enoyl-CoA = (E)-but-2-enoyl-CoA + CO₂

Glossary: (2E)-4-carboxybut-2-enoyl-CoA = glutaconyl-CoA
(E)-but-2-enoyl-CoA = crotonoyl-CoA

Other name(s): glutaryl coenzyme A dehydrogenase; glutaryl-CoA:(acceptor) 2,3-oxidoreductase (decarboxylating)

Systematic name: glutaryl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (decarboxylating)

Comments: Contains FAD. The enzyme catalyses the oxidation of glutaryl-CoA to glutaconyl-CoA (which remains bound to the enzyme), and the decarboxylation of the latter to crotonyl-CoA (cf. EC 4.1.1.70, glutaconyl-CoA decarboxylase). FAD is the electron acceptor in the oxidation of the substrate, and its reoxidation by electron-transfer flavoprotein completes the catalytic cycle.

References:

1. Besrat, A., Polan, C.E. and Henderson, L.M. Mammalian metabolism of glutaric acid. J. Biol. Chem. 244 (1969) 1461-1467. [PMID: 4304226]

2. Hartel, U., Eckel, E., Koch, J., Fuchs, G., Linder, D. and Buckel, W. Purification of glutaryl-CoA dehydrogenase from Pseudomonas sp., an enzyme involved in the anaerobic degradation of benzoate. Arch. Microbiol. 159 (1993) 174-181. [PMID: 8439237]

3. Dwyer, T.M., Zhang, L., Muller, M., Marrugo, F. and Frerman, F. The functions of the flavin contact residues, αArg²⁴⁹ and βTyr¹⁶, in human electron transfer flavoprotein. Biochim. Biophys. Acta 1433 (1999) 139-152. [PMID: 10446367]

4. Rao, K.S., Albro, M., Dwyer, T.M. and Frerman, F.E. Kinetic mechanism of glutaryl-CoA dehydrogenase. Biochemistry 45 (2006) 15853-15861. [PMID: 17176108]

EC 1.3.8.7

Accepted name: medium-chain acyl-CoA dehydrogenase

Reaction: a medium-chain acyl-CoA + electron-transfer flavoprotein = a medium-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein

Glossary: a medium-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 6 to 12 carbon atoms.

Other name(s): fatty acyl coenzyme A dehydrogenase (ambiguous); acyl coenzyme A dehydrogenase (ambiguous); acyl dehydrogenase (ambiguous); fatty-acyl-CoA dehydrogenase (ambiguous); acyl CoA dehydrogenase (ambiguous); general acyl CoA dehydrogenase (ambiguous); medium-chain acyl-coenzyme A dehydrogenase; acyl-CoA:(acceptor) 2,3-oxidoreductase (ambiguous); ACADM (gene name).

Systematic name: medium-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase

Comments: Contains FAD as prosthetic group. One of several enzymes that catalyse the first step in fatty acids β-oxidation. The enzyme from pig liver can accept substrates with acyl chain lengths of 4 to 16 carbon atoms, but is most active with C₈ to C₁₂ compounds [2]. The enzyme from rat does not accept C₁₆ at all and is most active with C₆-C₈ compounds [4]. cf. EC 1.3.8.1, short-chain acyl-CoA dehydrogenase, EC 1.3.8.8, long-chain acyl-CoA dehydrogenase, and EC 1.3.8.9, very-long-chain acyl-CoA dehydrogenase.

References:

1. Crane, F.L., Hauge, J.G. and Beinert, H. Flavoproteins involved in the first oxidative step of the fatty acid cycle. Biochim. Biophys. Acta 17 (1955) 292-294. [PMID: 13239683]

2. Crane, F.L., Mii, S., Hauge, J.G., Green, D.E. and Beinert, H. On the mechanism of dehydrogenation of fatty acyl derivatives of coenzyme A. I. The general fatty acyl coenzyme A dehydrogenase. J. Biol. Chem. 218 (1956) 701-716. [PMID: 13295224]

3. Beinert, H. Acyl coenzyme A dehydrogenase. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Eds), The Enzymes, 2nd edn, vol. 7, Academic Press, New York, 1963, pp. 447-466.

4. Ikeda, Y., Ikeda, K.O. and Tanaka, K. Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme. J. Biol. Chem. 260 (1985) 1311-1325. [PMID: 3968063]

5. Thorpe, C. and Kim, J.J. Structure and mechanism of action of the acyl-CoA dehydrogenases. FASEB J. 9 (1995) 718-725. [PMID: 7601336]

6. Kim, J.J., Wang, M. and Paschke, R. Crystal structures of medium-chain acyl-CoA dehydrogenase from pig liver mitochondria with and without substrate. Proc. Natl. Acad. Sci. USA 90 (1993) 7523-7527. [PMID: 8356049]

7. Peterson, K.L., Sergienko, E.E., Wu, Y., Kumar, N.R., Strauss, A.W., Oleson, A.E., Muhonen, W.W., Shabb, J.B. and Srivastava, D.K. Recombinant human liver medium-chain acyl-CoA dehydrogenase: purification, characterization, and the mechanism of interactions with functionally diverse C₈-CoA molecules. Biochemistry 34 (1995) 14942-14953. [PMID: 7578106]

8. Toogood, H.S., van Thiel, A., Basran, J., Sutcliffe, M.J., Scrutton, N.S. and Leys, D. Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex. J. Biol. Chem. 279 (2004) 32904-32912. [PMID: 15159392]

EC 1.3.8.8

Accepted name: long-chain acyl-CoA dehydrogenase

Reaction: a long-chain acyl-CoA + electron-transfer flavoprotein = a long-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein

Glossary: a long-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 13 to 22 carbon atoms.

Other name(s): palmitoyl-CoA dehydrogenase; palmitoyl-coenzyme A dehydrogenase; long-chain acyl-coenzyme A dehydrogenase; long-chain-acyl-CoA:(acceptor) 2,3-oxidoreductase; ACADL (gene name).

Systematic name: long-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase

Comments: Contains FAD as prosthetic group. One of several enzymes that catalyse the first step in fatty acids β-oxidation. The enzyme from pig liver can accept substrates with acyl chain lengths of 6 to at least 16 carbon atoms. The highest activity was found with C₁₂, and the rates with C₈ and C₁₆ were 80 and 70%, respectively [2]. The enzyme from rat can accept substrates with C₈-C₂₂. It is most active with C₁₄ and C₁₆, and has no activity with C₄, C₆ or C₂₄ [4]. cf. EC 1.3.8.1, short-chain acyl-CoA dehydrogenase, EC 1.3.8.8, medium-chain acyl-CoA dehydrogenase, and EC 1.3.8.9, very-long-chain acyl-CoA dehydrogenase.

References:

1. Crane, F.L., Hauge, J.G. and Beinert, H. Flavoproteins involved in the first oxidative step of the fatty acid cycle. Biochim. Biophys. Acta 17 (1955) 292-294. [PMID: 13239683]

2. Hauge, J.G., Crane, F.L. and Beinert, H. On the mechanism of dehydrogenation of fatty acyl derivatives of coenzyme A. III. Palmityl CoA dehydrogenase. J. Biol. Chem. 219 (1956) 727-733. [PMID: 13319294]

3. Hall, C.L., Heijkenkjold, L., Bartfai, T., Ernster, L. and Kamin, H. Acyl coenzyme A dehydrogenases and electron-transferring flavoprotein from beef heart mitochondria. Arch. Biochem. Biophys. 177 (1976) 402-414. [PMID: 1015826]

4. Ikeda, Y., Ikeda, K.O. and Tanaka, K. Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme. J. Biol. Chem. 260 (1985) 1311-1325. [PMID: 3968063]

5. Djordjevic, S., Dong, Y., Paschke, R., Frerman, F.E., Strauss, A.W. and Kim, J.J. Identification of the catalytic base in long chain acyl-CoA dehydrogenase. Biochemistry 33 (1994) 4258-4264. [PMID: 8155643]

EC 1.3.8.9

Accepted name: very-long-chain acyl-CoA dehydrogenase

Reaction: a very-long-chain acyl-CoA + electron-transfer flavoprotein = a very-long-chain trans-2,3-dehydroacyl-CoA + reduced electron-transfer flavoprotein

Glossary: a very-long-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 23 or more carbon atoms.

Other name(s): ACADVL (gene name).

Systematic name: very-long-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase

Comments: Contains FAD as prosthetic group. One of several enzymes that catalyse the first step in fatty acids β-oxidation. The enzyme is most active toward long-chain acyl-CoAs such as C₁₄, C₁₆ and C₁₈, but is also active with very-long-chain acyl-CoAs up to 24 carbons. It shows no activity for substrates of less than 12 carbons. Its specific activity towards palmitoyl-CoA is more than 10-fold that of the long-chain acyl-CoA dehydrogenase [1]. cf. EC 1.3.8.1, short-chain acyl-CoA dehydrogenase, EC 1.3.8.7, medium-chain acyl-CoA dehydrogenase, and EC 1.3.8.8, long-chain acyl-CoA dehydrogenase.

References:

1. Izai, K., Uchida, Y., Orii, T., Yamamoto, S. and Hashimoto, T. Novel fatty acid β-oxidation enzymes in rat liver mitochondria. I. Purification and properties of very-long-chain acyl-coenzyme A dehydrogenase. J. Biol. Chem. 267 (1992) 1027-1033. [PMID: 1730632]

2. Aoyama, T., Souri, M., Ushikubo, S., Kamijo, T., Yamaguchi, S., Kelley, R.I., Rhead, W.J., Uetake, K., Tanaka, K. and Hashimoto, T. Purification of human very-long-chain acyl-coenzyme A dehydrogenase and characterization of its deficiency in seven patients. J. Clin. Invest. 95 (1995) 2465-2473. [PMID: 7769092]

3. McAndrew, R.P., Wang, Y., Mohsen, A.W., He, M., Vockley, J. and Kim, J.J. Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. J. Biol. Chem. 283 (2008) 9435-9443. [PMID: 18227065]

[EC 1.3.99.3 Transferred entry: acyl-CoA dehydrogenase, now EC 1.3.8.7, medium-chain acyl-CoA dehydrogenase, EC 1.3.8.8, long-chain acyl-CoA dehydrogenase and EC 1.3.8.9, very-long-chain acyl-CoA dehydrogenase (EC 1.3.99.3 created 1961 as EC 1.3.2.2, transferred 1964 to EC 1.3.99.3, deleted 2012)]

[EC 1.3.99.7 Transferred entry: glutaryl-CoA dehydrogenase. Now EC 1.3.8.6, glutaryl-CoA dehydrogenase (EC 1.3.99.7 created 1972, deleted 2012)]

[EC 1.3.99.13 Transferred entry: long-chain-acyl-CoA dehydrogenase. Now EC 1.3.8.8, long-chain-acyl-CoA dehydrogenase (EC 1.3.99.13 created 1989, deleted 2012)]

EC 1.4.1.23

Accepted name: valine dehydrogenase (NAD⁺)

Reaction: L-valine + H₂O + NAD⁺ = 3-methyl-2-oxobutanoate + NH₃ + NADH + H⁺

Systematic name: L-valine:NAD⁺ oxidoreductase (deaminating)

Comments: The enzyme from Streptomyces spp. has no activity with NADP⁺ [cf. EC 1.4.1.8, valine dehydrogenase (NADP⁺)].

References:

1. Vancurová, I., Vancura, A., Volc, J., Neuzil, J., Flieger, M., Basarová, G. and Behal, V. Isolation and characterization of valine dehydrogenase from Streptomyces aureofaciens. J. Bacteriol. 170 (1988) 5192-5196. [PMID: 3182727]

2. Navarrete, R.M., Vara, J.A. and Hutchinson, C.R. Purification of an inducible L-valine dehydrogenase of Streptomyces coelicolor A3(2). J. Gen. Microbiol. 136 (1990) 273-281. [PMID: 2324704]

*EC 1.4.3.19

Accepted name: glycine oxidase

Reaction: glycine + H₂O + O₂ = glyoxylate + NH₃ + H₂O₂ (overall reaction)
(1a) glycine + O₂ = 2-iminoacetate + H₂O₂
(1b) 2-iminoglycine + H₂O = glyoxylate + NH₃

For diagram of reaction click here

Systematic name: glycine:oxygen oxidoreductase (deaminating)

Comments: A flavoenzyme containing non-covalently bound FAD. The enzyme from Bacillus subtilis is active with glycine, sarcosine, N-ethylglycine, D-alanine, D-α-aminobutyrate, D-proline, D-pipecolate and N-methyl-D-alanine. It differs from EC 1.4.3.3, D-amino-acid oxidase, due to its activity on sarcosine and D-pipecolate. The intermediate 2-iminoacetate is used directly by EC 2.8.1.10, thiazole synthase.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 39307-16-9

References:

1. Job, V., Marcone, G.L., Pilone, M.S. and Pollegioni, L. Glycine oxidase from Bacillus subtilis. Characterization of a new flavoprotein. J. Biol. Chem. 277 (2002) 6985-6993. [PMID: 11744710]

2. Nishiya, Y. and Imanaka, T. Purification and characterization of a novel glycine oxidase from Bacillus subtilis. FEBS Lett. 438 (1998) 263-266. [PMID: 9827558]

EC 1.13.11.63

Accepted name: β-carotene 15,15'-dioxygenase

Reaction: β-carotene + O₂ = 2 all-trans-retinal

For diagram of reaction click here.

Other name(s): blh (gene name)

Systematic name: β-carotene:oxygen 15,15'-dioxygenase (bond-cleaving)

Comments: Requires Fe²⁺. The enzyme, which has been characterized from the uncultured marine bacterium 66A03, is involved in the proteorhodopsin system, which uses retinal as its chromophore. The enzyme cleaves β-carotene symmetrically, producing two molecules of all-trans-retinal. Both atoms of the oxygen molecule are incorporated into the products. It requires a substrate greater than C₃₅ that contains at least one unsubstituted β-end group. cf. EC 1.14.99.36, β-carotene 15,15-monooxygenase.

References:

1. Kim, Y.S., Kim, N.H., Yeom, S.J., Kim, S.W. and Oh, D.K. In vitro characterization of a recombinant Blh protein from an uncultured marine bacterium as a β-carotene 15,15'-dioxygenase. J. Biol. Chem. 284 (2009) 15781-15793. [PMID: 19366683]

2. Kim, Y.S., Park, C.S. and Oh, D.K. Retinal production from β-carotene by β-carotene 15,15'-dioxygenase from an unculturable marine bacterium. Biotechnol. Lett. 32 (2010) 957-961. [PMID: 20229064]

EC 1.14.13.155

Accepted name: α-pinene monooxygenase

Reaction: (–)-α-pinene + NADH + H⁺ + O₂ = α-pinene oxide + NAD⁺ + H₂O

For diagram of reaction click here.

Systematic name: (–)-α-pinene,NADH:oxygen oxidoreductase

Comments: Involved in the catabolism of α-pinene.

References:

1. Colocousi, A. Saqib, K.M. and Leak, D.J. Mutants of Pseudomonas fuorescence NCIMB 11671 defective in the catabolism of α-pinene. Appl. Microbiol. Biotechnol. 45 (1996) 822-830.

EC 1.14.13.156

Accepted name: 1,8-cineole 2-endo-monooxygenase

Reaction: 1,8-cineole + NADPH + H⁺ + O₂ = 2-endo-hydroxy-1,8-cineole + NADP⁺ + H₂O

For diagram of reaction click here.

Other name(s): P450_cin; CYP176A; CYP176A1

Systematic name: 1,8-cineole,NADPH:oxygen oxidoreductase (2-endo-hydroxylating)

Comments: A heme-thiolate protein (P-450) which uses a flavodoxin-like redox partner to reduce the heme iron. Isolated from the bacterium Citrobacter braakii, which can use 1,8-cineole as the sole source of carbon.

References:

1. Hawkes, D.B., Adams, G.W., Burlingame, A.L., Ortiz de Montellano, P.R. and De Voss, J.J. Cytochrome P450_cin (CYP176A), isolation, expression, and characterization. J. Biol. Chem. 277 (2002) 27725-27732. [PMID: 12016226]

2. Meharenna, Y.T., Li, H., Hawkes, D.B., Pearson, A.G., De Voss, J. and Poulos, T.L. Crystal structure of P450_cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450_cam. Biochemistry 43 (2004) 9487-9494. [PMID: 15260491]

3. Kimmich, N., Das, A., Sevrioukova, I., Meharenna, Y., Sligar, S.G. and Poulos, T.L. Electron transfer between cytochrome P450_cin and its FMN-containing redox partner, cindoxin. J. Biol. Chem. 282 (2007) 27006-27011. [PMID: 17606612]

4. Meharenna, Y.T., Slessor, K.E., Cavaignac, S.M., Poulos, T.L. and De Voss, J.J. The critical role of substrate-protein hydrogen bonding in the control of regioselective hydroxylation in p450cin. J. Biol. Chem. 283 (2008) 10804-10812. [PMID: 18270198]

EC 1.14.13.157

Accepted name: 1,8-cineole 2-exo-monooxygenase

Reaction: 1,8-cineole + NADPH + H⁺ + O₂ = 2-exo-hydroxy-1,8-cineole + NADP⁺ + H₂O

For diagram of reaction click here.

Glossary: 1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
2-exo-hydroxy-1,8-cineole = (1R,4S,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol

Other name(s): CYP3A4

Systematic name: 1,8-cineole,NADPH:oxygen oxidoreductase (2-exo-hydroxylating)

Comments: A heme-thiolate protein (P-450). The mammalian enzyme, expressed in liver microsomes, performs a variety of oxidation reactions of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. cf. EC 1.14.13.97 (taurochenodeoxycholate 6-hydroxylase), EC 1.14.13.67 (quinine 3-monooxygenase) and EC 1.14.13.32 (albendazole monooxygenase).

References:

1. Miyazawa, M., Shindo, M. and Shimada, T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from Eucalyptus polybractea, by cytochrome P₄₅₀ 3A enzymes in rat and human liver microsomes. Drug Metab. Dispos. 29 (2001) 200-205. [PMID: 11159812]

2. Miyazawa, M. and Shindo, M. Biotransformation of 1,8-cineole by human liver microsomes. Nat. Prod. Lett. 15 (2001) 49-53. [PMID: 11547423]

3. Miyazawa, M., Shindo, M. and Shimada, T. Roles of cytochrome P₄₅₀ 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica 31 (2001) 713-723. [PMID: 11695850]

EC 1.14.13.158

Accepted name: amorpha-4,11-diene 12-monooxygenase

Reaction: amorpha-4,11-diene + 3 O₂ + 3 NADPH + 3 H⁺ = artemisinate + 3 NADP⁺ + 4 H₂O (overall reaction)
(1a) amorpha-4,11-diene + O₂ + NADPH + H⁺ = artemisinic alcohol + NADP⁺ + H₂O
(1b) artemisinic alcohol + O₂ + NADPH + H⁺ = artemisinic aldehyde + NADP⁺ + 2 H₂O
(1c) artemisinic aldehyde + O₂ + NADPH + H⁺ = artemisinate + NADP⁺ + H₂O

For diagram of reaction click here.

Other name(s): CYP71AV1

Systematic name: amorpha-4,11-diene,NADPH:oxygen oxidoreductase (12-hydroxylating)

Comments: A heme-thiolate protein (P-450). Cloned from the plant Artemisia annua (sweet wormwood). Part of the biosynthetic pathway of artemisinin.

References:

1. Teoh, K.H., Polichuk, D.R., Reed, D.W., Nowak, G. and Covello, P.S. Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin. FEBS Lett. 580 (2006) 1411-1416. [PMID: 16458889]

EC 1.14.13.159

Accepted name: vitamin D 25-hydroxylase

Reaction: calciol + O₂ + NADPH + H⁺ = calcidiol + NADP⁺ H₂O

For diagram of reaction click here.

Glossary: calciol = cholecalciferol = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3-ol = vitamin D₃
calcidiol = (3S,5Z,7E)-9,10-seco-5,7,10(19)-cholestatriene-3,25-diol

Other name(s): vitamin D₂ 25-hydroxylase; vitamin D₃ 25-hydroxylase; CYP2R1

Systematic name: calciol,NADPH:oxygen oxidoreductase (25-hydroxylating)

Comments: A microsomal enzyme isolated from human and mouse liver which bioactivates vitamin D₃. While multiple isoforms (CYP27A1, CYP2J2/3, CYP3A4, CYP2D25 and CYP2C11) are able to catalyse the reaction in vitro, only CYP2R1 is thought to catalyse the reaction in humans in vivo [4].

References:

1. Cheng, J.B., Motola, D.L., Mangelsdorf, D.J. and Russell, D.W. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J. Biol. Chem. 278 (2003) 38084-38093. [PMID: 12867411]

2. Shinkyo, R., Sakaki, T., Kamakura, M., Ohta, M. and Inouye, K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem. Biophys. Res. Commun. 324 (2004) 451-457. [PMID: 15465040]

3. Strushkevich, N., Usanov, S.A., Plotnikov, A.N., Jones, G. and Park, H.W. Structural analysis of CYP2R1 in complex with vitamin D₃. J. Mol. Biol. 380 (2008) 95-106. [PMID: 18511070]

4. Zhu, J. and Deluca, H.F. Vitamin D 25-hydroxylase - Four decades of searching, are we there yet ? Arch. Biochem. Biophys. (2012) . [PMID: 22310641]

EC 1.14.13.160

Accepted name: (2,2,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA 1,5-monooxygenase

Reaction: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetyl-CoA + O₂ + NADPH + H⁺ = [(2R)-3,3,4-trimethyl-6-oxo-3,6-dihydro-1H-pyran-2-yl]acetyl-CoA + NADP⁺ + H₂O

For diagram of reaction click here.

Glossary: (2,2,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA = 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetyl-CoA

Other name(s): 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase; 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetyl-CoA 1,2-monooxygenase; OTEMO

Systematic name: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetyl-CoA,NADPH:oxygen oxidoreductase (1,5-lactonizing)

Comments: A FAD dependent enzyme isolated from Pseudomonas putida. Forms part of the catabolism pathway of camphor. It acts on the CoA ester in preference to the free acid.

References:

1. Ougham, H.J., Taylor, D.G. and Trudgill, P.W. Camphor revisited: involvement of a unique monooxygenase in metabolism of 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetic acid by Pseudomonas putida. J. Bacteriol. 153 (1983) 140-152. [PMID: 6848481]

2. Leisch, H., Shi, R., Grosse, S., Morley, K., Bergeron, H., Cygler, M., Iwaki, H., Hasegawa, Y. and Lau, P.C. Cloning, Baeyer-Villiger biooxidations, and structures of the camphor pathway 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetyl-coenzyme A monooxygenase of Pseudomonas putida ATCC 17453. Appl. Environ. Microbiol. 78 (2012) 2200-2212. [PMID: 22267661]

3. Kadow, M., Loschinski, K., Sass, S., Schmidt, M. and Bornscheuer, U.T. Completing the series of BVMOs involved in camphor metabolism of Pseudomonas putida NCIMB 10007 by identification of the two missing genes, their functional expression in E. coli, and biochemical characterization. Appl. Microbiol. Biotechnol. (2012) . [PMID: 22286514]

EC 1.14.13.161

Accepted name: (+)-camphor 6-exo-hydroxylase

Reaction: (+)-camphor + NADPH + H⁺ + O₂ = (+)-6-exo-hydroxycamphor + NADP⁺ + H₂O

For diagram of reaction click here.

Other name(s): (+)-camphor 6-hydroxylase

Systematic name: (+)-camphor,NADPH:oxygen oxidoreductase (6-exo-hydroxylating)

Comments: A cytochrome P-450 monooxygenase isolated from Salvia officinalis (sage). Involved in the catabolism of camphor in senescent tissue.

References:

1. Funk, C., Koepp, A.E. and Croteau, R. Catabolism of camphor in tissue cultures and leaf disks of common sage (Salvia officinalis). Arch. Biochem. Biophys. 294 (1992) 306-313. [PMID: 1550356]

2. Funk, C. and Croteau, R. Induction and characterization of a cytochrome P-450-dependent camphor hydroxylase in tissue cultures of common sage (Salvia officinalis). Plant Physiol. 101 (1993) 1231-1237. [PMID: 12231778]

EC 1.14.13.162

Accepted name: 2,5-diketocamphane 1,2-monooxygenase

Reaction: (+)-bornane-2,5-dione + O₂ + NADH + H⁺ = (+)-5-oxo-1,2-campholide + NAD⁺ + H₂O

For diagram of reaction click here.

Glossary: 2,5-diketocamphane = (+)-bornane-2,5-dione

Other name(s): 2,5-diketocamphane lactonizing enzyme; ketolactonase I (ambiguous); 2,5-diketocamphane 1,2-monooxygenase oxygenating component; 2,5-DKCMO; camP (gene name); camphor 1,2-monooxygenase; camphor ketolactonase I

Systematic name: (+)-bornane-2,5-dione,NADH:oxygen oxidoreductase (1,2-lactonizing)

Comments: A flavoprotein (FMN) which requires Fe²⁺. A Baeyer-Villiger monooxygenase isolated from camphor-grown strains of Pseudomonas putida and encoded on the cam plasmid. Involved in the degradation of (+)-camphor. Requires a dedicated NADH-FMN reductase [cf. EC 1.5.1.42, FMN reductase (NADH)] [1-3]. Can accept several bicyclic ketones including (+)- and (–)-camphor [6] and adamantanone [4]. The product spontaneously converts to [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate.

References:

1. Conrad, H.E., DuBus, R., Namtvedt, M.J. and Gunsalus, I.C. Mixed function oxidation. II. Separation and properties of the enzymes catalyzing camphor lactonizaton. J. Biol. Chem. 240 (1965) 495-503. [PMID: 14253460]

2. Yu, C.A. and Gunsalus, I.C. Monoxygenases. VII. Camphor ketolactonase I and the role of three protein components. J. Biol. Chem. 244 (1969) 6149-6152. [PMID: 4310834]

3. Taylor, D.G. and Trudgill, P.W. Camphor revisited: studies of 2,5-diketocamphane 1,2-monooxygenase from Pseudomonas putida ATCC 17453. J. Bacteriol. 165 (1986) 489-497. [PMID: 3944058]

4. Selifonov, S.A. Microbial oxidation of adamantanone by Pseudomonas putida carrying the camphor catabolic plasmid. Biochem. Biophys. Res. Commun. 186 (1992) 1429-1436. [PMID: 1510672]

5. Jones, K.H., Smith, R.T. and Trudgill, P.W. Diketocamphane enantiomer-specific 'Baeyer-Villiger' monooxygenases from camphor-grown Pseudomonas putida ATCC 17453. J. Gen. Microbiol. 139 (1993) 797-805. [PMID: 8515237]

6. Kadow, M., Sass, S., Schmidt, M. and Bornscheuer, U.T. Recombinant expression and purification of the 2,5-diketocamphane 1,2-monooxygenase from the camphor metabolizing Pseudomonas putida strain NCIMB 10007. AMB Express 1 (2011) 13. [PMID: 21906366]

[EC 1.14.15.2 Transferred entry: camphor 1,2-monooxygenase. Now EC 1.14.13.162, 2,5-diketocamphane 1,2-monooxygenase (EC 1.14.15.2 created 1972, deleted 2012)]

EC 1.14.15.9

Accepted name: spheroidene monooxygenase

Reaction: (1) spheroidene + reduced ferredoxin + O₂ = spheroiden-2-one + oxidized ferredoxin + H₂O
(2) spirilloxantin + reduced ferredoxin + O₂ = 2-oxospirilloxanthin + oxidized ferredoxin + H₂O
(3) 2'-oxospirilloxanthin + reduced ferredoxin + O₂ = 2,2'-dioxospirilloxanthin + oxidized ferredoxin + H₂O

For diagram of reaction click here or click here.

Glossary: spheroidene = 1-methoxy-3,4-didehydro-1,2,7',8'-tetrahydro-ψ,ψ-carotene

Other name(s): CrtA; acyclic carotenoid 2-ketolase; spirilloxantin monooxygenase; 2-oxo-spirilloxanthin monooxygenase

Systematic name: spheroidene,reduced-ferredoxin:oxygen oxidoreductase (spheroiden-2-one-forming)

Comments: The enzyme is involved in spheroidenone biosynthesis and in 2,2'-dioxospirilloxanthin biosynthesis. The enzyme from Rhodobacter sphaeroides contains heme at its active site [1].

References:

1. Lee, P.C., Holtzapple, E. and Schmidt-Dannert, C. Novel activity of Rhodobacter sphaeroides spheroidene monooxygenase CrtA expressed in Escherichia coli. Appl. Environ. Microbiol. 76 (2010) 7328-7331. [PMID: 20851979]

2. Gerjets, T., Steiger, S. and Sandmann, G. Catalytic properties of the expressed acyclic carotenoid 2-ketolases from Rhodobacter capsulatus and Rubrivivax gelatinosus. Biochim. Biophys. Acta 1791 (2009) 125-131. [PMID: 19136077]

EC 1.14.15.10

Accepted name: (+)-camphor 6-endo-hydroxylase

Reaction: (+)-camphor + reduced putidaredoxin + O₂ = (+)-6-endo-hydroxycamphor + oxidized putidaredoxin + H₂O

For diagram of reaction click here.

Other name(s): P450_camr

Systematic name: (+)-camphor,reduced putidaredoxin:oxygen oxidoreductase (6-endo-hydroxylating)

Comments: A cytochrome P-450 monooxygenase from the bacterium Rhodococcus sp. NCIMB 9784.

References:

1. Grogan, G., Roberts, G.A., Parsons, S., Turner, N.J. and Flitsch, S.L. P450_camr, a cytochrome P450 catalysing the stereospecific 6-endo-hydroxylation of (1R)-(+)-camphor. Appl. Microbiol. Biotechnol. 59 (2002) 449-454. [PMID: 12172608]

EC 1.18.1.5

Accepted name: putidaredoxin—NAD⁺ reductase

Reaction: reduced putidaredoxin + NAD⁺ = oxidized putidaredoxin + NADH + H⁺

For diagram of reaction click here.

Other name(s): putidaredoxin reductase; camA (gene name)

Systematic name: putidaredoxin:NAD⁺ oxidoreductase

Comments: Requires FAD. The enzyme from Pseudomonas putida reduces putidaredoxin. It contains a [2Fe-2S] cluster. Involved in the camphor monooxygenase system (see EC 1.14.15.1, camphor 5-monooxygenase).

References:

1. Roome, P.W., Jr., Philley, J.C. and Peterson, J.A. Purification and properties of putidaredoxin reductase. J. Biol. Chem. 258 (1983) 2593-2598. [PMID: 6401738]

2. Koga, H., Yamaguchi, E., Matsunaga, K., Aramaki, H. and Horiuchi, T. Cloning and nucleotide sequences of NADH-putidaredoxin reductase gene (camA) and putidaredoxin gene (camB) involved in cytochrome P-450_cam hydroxylase of Pseudomonas putida. J. Biochem. 106 (1989) 831-836. [PMID: 2613690]

3. Peterson, J.A., Lorence, M.C. and Amarneh, B. Putidaredoxin reductase and putidaredoxin. Cloning, sequence determination, and heterologous expression of the proteins. J. Biol. Chem. 265 (1990) 6066-6073. [PMID: 2180940]

4. Sevrioukova, I.F. and Poulos, T.L. Putidaredoxin reductase, a new function for an old protein. J. Biol. Chem. 277 (2002) 25831-25839. [PMID: 12011076]

5. Sevrioukova, I.F., Garcia, C., Li, H., Bhaskar, B. and Poulos, T.L. Crystal structure of putidaredoxin, the [2Fe-2S] component of the P450_cam monooxygenase system from Pseudomonas putida. J. Mol. Biol. 333 (2003) 377-392. [PMID: 14529624]

6. Sevrioukova, I.F., Li, H. and Poulos, T.L. Crystal structure of putidaredoxin reductase from Pseudomonas putida, the final structural component of the cytochrome P450_cam monooxygenase. J. Mol. Biol. 336 (2004) 889-902. [PMID: 15095867]

7. Smith, N., Mayhew, M., Holden, M.J., Kelly, H., Robinson, H., Heroux, A., Vilker, V.L. and Gallagher, D.T. Structure of C73G putidaredoxin from Pseudomonas putida. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 816-822. [PMID: 15103126]

EC 2.1.1.256

Accepted name: tRNA (guanine⁶-N²)-methyltransferase

Reaction: S-adenosyl-L-methionine + guanine⁶ in tRNA = S-adenosyl-L-homocysteine + N²-methylguanine⁶ in tRNA

Other name(s): methyltransferase Trm14; m²G⁶ methyltransferase

Systematic name: S-adenosyl-L-methionine:tRNA (guanine⁶-N²)-methyltransferase

Comments: The enzyme specifically methylates guanine⁶ at N² in tRNA.

References:

1. Menezes, S., Gaston, K.W., Krivos, K.L., Apolinario, E.E., Reich, N.O., Sowers, K.R., Limbach, P.A. and Perona, J.J. Formation of m²G⁶ in Methanocaldococcus jannaschii tRNA catalyzed by the novel methyltransferase Trm14. Nucleic Acids Res. 39 (2011) 7641-7655. [PMID: 21693558]

EC 2.1.1.257

Accepted name: tRNA (pseudouridine⁵⁴-N¹)-methyltransferase

Reaction: S-adenosyl-L-methionine + pseudouridine⁵⁴ in tRNA = S-adenosyl-L-homocysteine + N¹-methylpseudouridine⁵⁴ in tRNA

Other name(s): TrmY; m¹Ψ methyltransferase

Systematic name: S-adenosyl-L-methionine:tRNA (pseudouridine⁵⁴-N¹)-methyltransferase

Comments: While this archaeal enzyme is specific for the 54 position and does not methylate pseudouridine at position 55, the presence of pseudouridine at position 55 is necessary for the efficient methylation of pseudouridine at position 54 [2,3].

References:

1. Chen, H.Y. and Yuan, Y.A. Crystal structure of Mj1640/DUF358 protein reveals a putative SPOUT-class RNA methyltransferase. J. Mol. Cell. Biol. 2 (2010) 366-374. [PMID: 21098051]

2. Wurm, J.P., Griese, M., Bahr, U., Held, M., Heckel, A., Karas, M., Soppa, J. and Wohnert, J. Identification of the enzyme responsible for N¹-methylation of pseudouridine 54 in archaeal tRNAs. RNA 18 (2012) 412-420. [PMID: 22274954]

3. Chatterjee, K., Blaby, I.K., Thiaville, P.C., Majumder, M., Grosjean, H., Yuan, Y.A., Gupta, R. and de Crecy-Lagard, V. The archaeal COG1901/DUF358 SPOUT-methyltransferase members, together with pseudouridine synthase Pus10, catalyze the formation of 1-methylpseudouridine at position 54 of tRNA. RNA 18 (2012) 421-433. [PMID: 22274953]

EC 2.2.1.10

Accepted name: 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate synthase

Reaction: L-aspartate 4-semialdehyde + 1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate = 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate + 2,3-dioxopropyl phosphate

For diagram of reaction click here.

Glossary: 1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate = 6-deoxy-5-ketofructose 1-phosphate
2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate = 2-amino-2,3,7-trideoxy-D-lyxo-hept-6-ulosonate

Other name(s): ADH synthase; ADHS; MJ0400 (gene name)

Systematic name: L-aspartate 4-semialdehyde:1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate methylglyoxaltransferase

Comments: The enzyme plays a key role in an alternative pathway of the biosynthesis of 3-dehydroquinate (DHQ), which is involved in the canonical pathway for the biosynthesis of aromatic amino acids. The enzyme can also catalyse the reaction of EC 4.1.2.13, fructose-bisphosphate aldolase.

References:

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

2. Samland, A.K., Wang, M. and Sprenger, G.A. MJ0400 from Methanocaldococcus jannaschii exhibits fructose-1,6-bisphosphate aldolase activity. FEMS Microbiol. Lett. 281 (2008) 36-41. [PMID: 18318840]

3. Morar, M., White, R.H. and Ealick, S.E. Structure of 2-amino-3,7-dideoxy-D-threo-hept-6-ulosonic acid synthase, a catalyst in the archaeal pathway for the biosynthesis of aromatic amino acids. Biochemistry 46 (2007) 10562-10571. [PMID: 17713928]

EC 2.2.1.11

Accepted name: 6-deoxy-5-ketofructose 1-phosphate synthase

Reaction: (1) methylglyoxal + D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-phosphate + 1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate
(2) methylglyoxal + D-fructose 1-phosphate = D-glyceraldehyde + 1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate

For diagram of reaction click here.

Glossary: methylglyoxal = 2-oxopropanal
1-deoxy-D-threo-hexo-2,5-diulose 6-phosphate = 6-deoxy-5-ketofructose 1-phosphate

Other name(s): DKFP synthase; MJ1585 (gene name)

Systematic name: 2-oxopropanal:D-fructose 1,6-bisphosphate glycerone-phosphotransferase

Comments: The enzyme plays a key role in an alternative pathway of the biosynthesis of 3-dehydroquinate (DHQ), which is involved in the canonical pathway for the biosynthesis of aromatic amino acids. The enzyme can also catalyse the reaction of EC 4.1.2.13, fructose-bisphosphate aldolase.

References:

1. White, R.H. and Xu, H. Methylglyoxal is an intermediate in the biosynthesis of 6-deoxy-5-ketofructose-1-phosphate: a precursor for aromatic amino acid biosynthesis in Methanocaldococcus jannaschii. Biochemistry 45 (2006) 12366-12379. [PMID: 17014089]

2. Samland, A.K., Wang, M. and Sprenger, G.A. MJ0400 from Methanocaldococcus jannaschii exhibits fructose-1,6-bisphosphate aldolase activity. FEMS Microbiol. Lett. 281 (2008) 36-41. [PMID: 18318840]

EC 2.3.1.198

Accepted name: glycerol-3-phosphate 2-O-acyltransferase

Reaction: an acyl-CoA + sn-glycerol 3-phosphate = CoA + a 2-acyl-sn-glycerol 3-phosphate

Other name(s): sn-2-glycerol-3-phosphate O-acyltransferase; glycerol-3-phosphate O-acyltransferase (ambiguous)

Systematic name: acyl-CoA:sn-glycerol 3-phosphate 2-O-acyltransferase

Comments: A membrane-associated enzyme required for suberin or cutin synthesis in plants. Active with a wide range of acyl-CoA substrates (C16:0-C24:0). The enzyme from some sources has much higher activity with ω-oxidized acyl-CoAs. Some enzymes are bifunctional and have an additional phosphatase activity producing sn-2-monoacylglycerols. Can also catalyse the reaction of EC 2.3.1.15 (glycerol-3-phosphate 1-O-acyltransferase), but less well.

References:

1. Yang, W., Pollard, M., Li-Beisson, Y., Beisson, F., Feig, M. and Ohlrogge, J. A distinct type of glycerol-3-phosphate acyltransferase with sn-2 preference and phosphatase activity producing 2-monoacylglycerol. Proc. Natl. Acad. Sci. USA 107 (2010) 12040-12045. [PMID: 20551224]

*EC 2.4.1.132

Accepted name: GDP-Man:Man₁GlcNAc₂-PP-dolichol α-1,3-mannosyltransferase

Reaction: GDP-D-mannose + D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol = GDP + D-Man-α-(1→3)-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol

For diagram of reaction click here

Other name(s): Alg2 mannosyltransferase (ambiguous); ALG2 (gene name, ambiguous); glycolipid 3-α-mannosyltransferase; GDP-mannose:glycolipid 3-α-D-mannosyltransferase; GDP-Man:Man₁GlcNAc₂-PP-Dol α-1,3-mannosyltransferase

Systematic name: GDP-D-mannose:D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol 3-α-mannosyltransferase

Comments: The biosynthesis of asparagine-linked glycoproteins utilizes a dolichyl diphosphate-linked glycosyl donor, which is assembled by the series of membrane-bound glycosyltransferases that comprise the dolichol pathway. Alg2 mannosyltransferase from Saccharomyces cerevisiae carries out an α1,3-mannosylation of D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol, followed by an α1,6-mannosylation (cf. EC 2.4.1.257), to form the first branched pentasaccharide intermediate of the dolichol pathway [1,2].

Links to other databases: BRENDA, EXPASY, KEGG, CAS registry number: 81181-76-2

References:

1. Kampf, M., Absmanner, B., Schwarz, M. and Lehle, L. Biochemical characterization and membrane topology of Alg2 from Saccharomyces cerevisiae as a bifunctional α1,3- and 1,6-mannosyltransferase involved in lipid-linked oligosaccharide biosynthesis. J. Biol. Chem. 284 (2009) 11900-11912. [PMID: 19282279]

2. O'Reilly, M.K., Zhang, G. and Imperiali, B. In vitro evidence for the dual function of Alg2 and Alg11: essential mannosyltransferases in N-linked glycoprotein biosynthesis. Biochemistry 45 (2006) 9593-9603. [PMID: 16878994]

*EC 2.4.1.258

Accepted name: dolichyl-P-Man:Man₅GlcNAc₂-PP-dolichol α-1,3-mannosyltransferase

Reaction: dolichyl β-D-mannosyl phosphate + D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol = D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→3)-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate

For diagram of reaction click here

Other name(s): Man₅GlcNAc₂-PP-Dol mannosyltransferase; ALG3; dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase; Not56-like protein; Alg3 α-1,3-mannosyl transferase; Dol-P-Man:Man₅GlcNAc₂-PP-Dol α-1,3-mannosyltransferase

Systematic name: dolichyl β-D-mannosyl phosphate:D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol α-1,3-mannosyltransferase

Comments: The formation of N-glycosidic linkages of glycoproteins involves the ordered assembly of the common Glc₃Man₉GlcNAc₂ core-oligosaccharide on the lipid carrier dolichyl diphosphate. Early mannosylation steps occur on the cytoplasmic side of the endoplasmic reticulum with GDP-Man as donor, the final reactions from Man₅GlcNAc₂-PP-dolichol to Man₉Glc-NAc₂-PP-dolichol on the lumenal side use dolichyl β-D-mannosyl phosphate. The first step of this assembly pathway on the luminal side of the endoplasmic reticulum is catalysed by ALG3.

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

References:

1. Sharma, C.B., Knauer, R. and Lehle, L. Biosynthesis of lipid-linked oligosaccharides in yeast: the ALG3 gene encodes the Dol-P-Man:Man₅GlcNAc₂-PP-Dol mannosyltransferase. Biol. Chem. 382 (2001) 321-328. [PMID: 11308030]

2. Cipollo, J.F. and Trimble, R.B. The accumulation of Man(6)GlcNAc(2)-PP-dolichol in the Saccharomyces cerevisiae Δalg9 mutant reveals a regulatory role for the Alg3p α1,3-Man middle-arm addition in downstream oligosaccharide-lipid and glycoprotein glycan processing. J. Biol. Chem. 275 (2000) 4267-4277. [PMID: 10660594]

*EC 2.4.1.259

Accepted name: dolichyl-P-Man:Man₆GlcNAc₂-PP-dolichol α-1,2-mannosyltransferase

Reaction: dolichyl β-D-mannosyl phosphate + D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→3)-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol = D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate

For diagram of reaction click here

Other name(s): ALG9; ALG9 α1,2 mannosyltransferase; dolichylphosphomannose-dependent ALG9 mannosyltransferase; ALG9 mannosyltransferase; Dol-P-Man:Man₆GlcNAc₂-PP-Dol α-1,2-mannosyltransferase

Systematic name: dolichyl β-D-mannosyl phosphate:D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→3)-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol α-1,2-mannosyltransferase

Comments: The formation of N-glycosidic linkages of glycoproteins involves the ordered assembly of the common Glc₃Man₉GlcNAc₂ core-oligosaccharide on the lipid carrier dolichyl diphosphate. Early mannosylation steps occur on the cytoplasmic side of the endoplasmic reticulum with GDP-Man as donor, the final reactions from Man₅GlcNAc₂-PP-Dol to Man₉Glc-NAc₂-PP-Dol on the lumenal side use dolichyl β-D-mannosyl phosphate. ALG9 mannosyltransferase catalyses the addition of two different α-1,2-mannose residues - the addition of α-1,2-mannose to Man₆GlcNAc₂-PP-Dol (EC 2.4.1.259) and the addition of α-1,2-mannose to Man₈GlcNAc₂-PP-Dol (EC 2.4.1.261).

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

References:

1. Vleugels, W., Keldermans, L., Jaeken, J., Butters, T.D., Michalski, J.C., Matthijs, G. and Foulquier, F. Quality control of glycoproteins bearing truncated glycans in an ALG9-defective (CDG-IL) patient. Glycobiology 19 (2009) 910-917. [PMID: 19451548]

2. Cipollo, J.F. and Trimble, R.B. The accumulation of Man(6)GlcNAc(2)-PP-dolichol in the Saccharomyces cerevisiae Δalg9 mutant reveals a regulatory role for the Alg3p α1,3-Man middle-arm addition in downstream oligosaccharide-lipid and glycoprotein glycan processing. J. Biol. Chem. 275 (2000) 4267-4277. [PMID: 10660594]

3. Frank, C.G. and Aebi, M. ALG9 mannosyltransferase is involved in two different steps of lipid-linked oligosaccharide biosynthesis. Glycobiology 15 (2005) 1156-1163. [PMID: 15987956]

*EC 2.4.1.260

Accepted name: dolichyl-P-Man:Man₇GlcNAc₂-PP-dolichol α-1,6-mannosyltransferase

Reaction: dolichyl β-D-mannosyl phosphate + D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol = D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate

For diagram of reaction click here

Other name(s): ALG12; ALG12 mannosyltransferase; ALG12 α1,6mannosyltransferase; dolichyl-P-mannose:Man₇GlcNAc₂-PP-dolichyl mannosyltransferase; dolichyl-P-Man:Man₇GlcNAc₂-PP-dolichyl α6-mannosyltransferase; EBS4; Dol-P-Man:Man₇GlcNAc₂-PP-Dol α-1,6-mannosyltransferase

Systematic name: dolichyl β-D-mannosyl phosphate:D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol α-1,6-mannosyltransferase

Comments: The formation of N-glycosidic linkages of glycoproteins involves the ordered assembly of the common Glc₃Man₉GlcNAc₂ core-oligosaccharide on the lipid carrier dolichyl diphosphate. Early mannosylation steps occur on the cytoplasmic side of the endoplasmic reticulum with GDP-Man as donor, the final reactions from Man₅GlcNAc₂-PP-Dol to Man₉Glc-NAc₂-PP-Dol on the lumenal side use dolichyl β-D-mannosyl phosphate.

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

References:

1. Frank, C.G. and Aebi, M. ALG9 mannosyltransferase is involved in two different steps of lipid-linked oligosaccharide biosynthesis. Glycobiology 15 (2005) 1156-1163. [PMID: 15987956]

2. Hong, Z., Jin, H., Fitchette, A.C., Xia, Y., Monk, A.M., Faye, L. and Li, J. Mutations of an α1,6 mannosyltransferase inhibit endoplasmic reticulum-associated degradation of defective brassinosteroid receptors in Arabidopsis. Plant Cell 21 (2009) 3792-3802. [PMID: 20023196]

3. Cipollo, J.F. and Trimble, R.B. The Saccharomyces cerevisiae alg12δ mutant reveals a role for the middle-arm α1,2Man- and upper-arm α1,2Manα1,6Man- residues of Glc₃Man₉GlcNAc₂-PP-Dol in regulating glycoprotein glycan processing in the endoplasmic reticulum and Golgi apparatus. Glycobiology 12 (2002) 749-762. [PMID: 12460943]

4. Grubenmann, C.E., Frank, C.G., Kjaergaard, S., Berger, E.G., Aebi, M. and Hennet, T. ALG12 mannosyltransferase defect in congenital disorder of glycosylation type lg. Hum. Mol. Genet. 11 (2002) 2331-2339. [PMID: 12217961]

*EC 2.4.1.265

Accepted name: dolichyl-P-Glc:Glc₁Man₉GlcNAc₂-PP-dolichol α-1,3-glucosyltransferase

Reaction: dolichyl β-D-glucosyl phosphate + D-Glc-α-(1→3)-D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol = D-Glc-α-(1→3)-D-Glc-α-(1→3)-D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate

For diagram of reaction click here

Other name(s): ALG8; Dol-P-Glc:Glc₁Man₉GlcNAc₂-PP-Dol α-1,3-glucosyltransferase

Systematic name: dolichyl β-D-glucosyl phosphate:D-Glc-α-(1→3)-D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol α-1,3-glucosyltransferase

Comments: The successive addition of three glucose residues by EC 2.4.1.267 (dolichyl-P-Glc:Man₉GlcNAc₂-PP-dolichol α-1,3-glucosyltransferase), EC 2.4.1.265 and EC 2.4.1.256 (dolichyl-P-Glc:Glc₂Man₉GlcNAc₂-PP-dolichol α-1,2-glucosyltransferase) represents the final stage of the lipid-linked oligosaccharide assembly.

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

References:

1. Stagljar, I., te Heesen, S. and Aebi, M. New phenotype of mutations deficient in glucosylation of the lipid-linked oligosaccharide: cloning of the ALG8 locus. Proc. Natl. Acad. Sci. USA 91 (1994) 5977-5981. [PMID: 8016100]

2. Runge, K.W. and Robbins, P.W. A new yeast mutation in the glucosylation steps of the asparagine-linked glycosylation pathway. Formation of a novel asparagine-linked oligosaccharide containing two glucose residues. J. Biol. Chem. 261 (1986) 15582-15590. [PMID: 3536907]

3. Chantret, I., Dancourt, J., Dupre, T., Delenda, C., Bucher, S., Vuillaumier-Barrot, S., Ogier de Baulny, H., Peletan, C., Danos, O., Seta, N., Durand, G., Oriol, R., Codogno, P. and Moore, S.E. A deficiency in dolichyl-P-glucose:Glc₁Man₉GlcNAc₂-PP-dolichyl α3-glucosyltransferase defines a new subtype of congenital disorders of glycosylation. J. Biol. Chem. 278 (2003) 9962-9971. [PMID: 12480927]

*EC 2.4.1.267

Accepted name: dolichyl-P-Glc:Man₉GlcNAc₂-PP-dolichol α-1,3-glucosyltransferase

Reaction: dolichyl β-D-glucosyl phosphate + D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol = D-Glc-α-(1→3)-D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol + dolichyl phosphate

For diagram of reaction click here

Other name(s): ALG6; Dol-P-Glc:Man₉GlcNAc₂-PP-Dol α-1,3-glucosyltransferase

Systematic name: dolichyl β-D-glucosyl phosphate:D-Man-α-(1→2)-D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→3)-[D-Man-α-(1→2)-D-Man-α-(1→6)]-D-Man-α-(1→6)]-D-Man-β-(1→4)-D-GlcNAc-β-(1→4)-D-GlcNAc-diphosphodolichol α-1,3-glucosyltransferase

Comments: The successive addition of three glucose residues by EC 2.4.1.267, EC 2.4.1.265 (Dol-P-Glc:Glc₁Man₉GlcNAc₂-PP-Dol α-1,3-glucosyltransferase) and EC 2.4.1.256 (Dol-P-Glc:Glc₂Man₉GlcNAc₂-PP-Dol α-1,2-glucosyltransferase) represents the final stage of the lipid-linked oligosaccharide assembly.

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

References:

1. Reiss, G., te Heesen, S., Zimmerman, J., Robbins, P.W. and Aebi, M. Isolation of the ALG6 locus of Saccharomyces cerevisiae required for glucosylation in the N-linked glycosylation pathway. Glycobiology 6 (1996) 493-498. [PMID: 8877369]

2. Runge, K.W., Huffaker, T.C. and Robbins, P.W. Two yeast mutations in glucosylation steps of the asparagine glycosylation pathway. J. Biol. Chem. 259 (1984) 412-417. [PMID: 6423630]

3. Westphal, V., Xiao, M., Kwok, P.Y. and Freeze, H.H. Identification of a frequent variant in ALG6, the cause of congenital disorder of glycosylation-Ic. Hum. Mutat. 22 (2003) 420-421. [PMID: 14517965]

*EC 2.4.2.29

Accepted name: tRNA-guanosine³⁴ transglycosylase

Reaction: (1) guanine³⁴ in tRNA + queuine = queuine34 in tRNA + guanine
(2) guanine³⁴ in tRNA + 7-aminomethyl-7-carbaguanine = 7-aminomethyl-7-carbaguanine³⁴ in tRNA + guanine

For diagram of reaction click here

Glossary: 7-aminomethyl-7-carbaguanine = preQ₁ = 7-aminomethyl-7-deazaguanine
7-cyano-7-carbaguanine = preQ₀ = 7-cyano-7-deazaguanine
queuine = base Q = 2-amino-5-({[(1S,4S,5R)-4,5-dihydroxycyclopent-2-en-1-yl]amino}methyl)-1,7-dihydropyrrolo[3,2-e]pyrimidin-4-one

Other name(s): guanine insertion enzyme (ambiguous); tRNA transglycosylase (ambiguous); Q-insertase (ambiguous); queuine34 transfer ribonucleate ribosyltransferase; transfer ribonucleate glycosyltransferase (ambiguous); tRNA guanine³⁴ transglycosidase; queuine tRNA-ribosyltransferase (ambiguous); TGT; [tRNA]-guanine³⁴:queuine tRNA-D-ribosyltransferase; transfer ribonucleic acid guanine³⁴ transglycosylase

Systematic name: tRNA-guanosine³⁴:queuine tRNA-D-ribosyltransferase

Comments: Certain prokaryotic and eukaryotic tRNAs contain the modified base queuine at position 34. In eukaryotes queuine is salvaged from food and incorporated into tRNA directly via a base-exchange reaction, replacing guanine. In eubacteria, which produce queuine de novo, the enzyme catalyses the exchange of guanine with the queuine precursor preQ₁, which is ultimately modified to queuosine [4,5]. The eubacterial enzyme can also use an earlier intermediate, preQ₀, to replace guanine in unmodified tRNA^Tyr and tRNA^Asn [2]. This enzyme acts after EC 1.7.1.13, preQ₁ synthase, in the queuine-biosynthesis pathway.

Links to other databases: BRENDA, EXPASY, KEGG, PDB, CAS registry number: 72162-89-1

References:

1. Howes, N.K. and Farkas, W.R. Studies with a homogeneous enzyme from rabbit erythrocytes catalyzing the insertion of guanine into tRNA. J. Biol. Chem. 253 (1978) 9082-9087. [PMID: 721832]

2. Okada, N., Noguchi, S., Kasai, H., Shindo-Okada, N., Ohgi, T., Goto, T. and Nishimura, S. Novel mechanism of post-transcriptional modification of tRNA. Insertion of bases of Q precursors into tRNA by a specific tRNA transglycosylase reaction. J. Biol. Chem. 254 (1979) 3067-3073. [PMID: 372186]

3. Shindo-Okada, N., Okada, N., Ohgi, T., Goto, T. and Nishimura, S. Transfer ribonucleic acid guanine transglycosylase isolated from rat liver. Biochemistry 19 (1980) 395-400. [PMID: 6986171]

4. Todorov, K.A. and Garcia, G.A. Role of aspartate 143 in Escherichia coli tRNA-guanine transglycosylase: alteration of heterocyclic substrate specificity. Biochemistry 45 (2006) 617-625. [PMID: 16401090]

5. Boland, C., Hayes, P., Santa-Maria, I., Nishimura, S. and Kelly, V.P. Queuosine formation in eukaryotic tRNA occurs via a mitochondria-localized heteromeric transglycosylase. J. Biol. Chem. 284 (2009) 18218-18227. [PMID: 19414587]

EC 3.7.1.18

Accepted name: 6-oxocamphor hydrolase

Reaction: bornane-2,6-dione + H₂O = [(1S)-4-hydroxy-2,2,3-trimethylcyclopent-3-enyl]acetate

For diagram of reaction click here and mechanism click here.

Glossary: α-campholonate = (4-hydroxy-2,2,3-trimethylcyclopent-3-enyl)acetate (enol form) = (2,2,3-trimethyl-4-oxocyclopentyl)acetate (keto form)

Other name(s): OCH; camK (gene name)

Systematic name: bornane-2,6-dione hydrolase

Comments: Isolated from Rhodococcus sp. The bornane ring system is cleaved by a retro-Claisen reaction to give the enol of α-campholonate. When separate from the enzyme the enol is tautomerised to the keto form as a 6:1 mixture of [(1S,3R)-2,2,3-trimethyl-4-oxocyclopentyl]acetate and [(1S,3S)-2,2,3-trimethyl-4-oxocyclopentyl]acetate.

References:

1. Grogan, G., Roberts, G.A., Bougioukou, D., Turner, N.J. and Flitsch, S.L. The desymmetrization of bicyclic β-diketones by an enzymatic retro-Claisen reaction. A new reaction of the crotonase superfamily. J. Biol. Chem. 276 (2001) 12565-12572. [PMID: 11278926]

2. Whittingham, J.L., Turkenburg, J.P., Verma, C.S., Walsh, M.A. and Grogan, G. The 2-Å crystal structure of 6-oxo camphor hydrolase. New structural diversity in the crotonase superfamily. J. Biol. Chem. 278 (2003) 1744-1750. [PMID: 12421807]

3. Leonard, P.M. and Grogan, G. Structure of 6-oxo camphor hydrolase H122A mutant bound to its natural product, (2S,4S)-α-campholinic acid: mutant structure suggests an atypical mode of transition state binding for a crotonase homolog. J. Biol. Chem. 279 (2004) 31312-31317. [PMID: 15138275]

EC 4.2.1.133

Accepted name: copal-8-ol diphosphate hydratase

Reaction: (13E)-8α-hydroxylabda-13-en-15-yl diphosphate = geranylgeranyl diphosphate + H₂O

For diagram of reaction click here.

Glossary: (13E)-8α-hydroxylabda-13-en-15-yl diphosphate = copal-8-ol diphosphate

Other name(s): CcCLS

Systematic name: geranylgeranyl-diphosphate hydro-lyase [(13E)-8α-hydroxylabda-13-en-15-yl diphosphate forming]

Comments: Requires Mg²⁺. The enzyme was characterized from the plant Cistus creticus subsp. creticus.

References:

1. Falara, V., Pichersky, E. and Kanellis, A.K. A copal-8-ol diphosphate synthase from the angiosperm Cistus creticus subsp. creticus is a putative key enzyme for the formation of pharmacologically active, oxygen-containing labdane-type diterpenes. Plant Physiol. 154 (2010) 301-310. [PMID: 20595348]

EC 4.2.3.124

Accepted name: 2-deoxy-scyllo-inosose synthase

Reaction: D-glucose 6-phosphate = 2-deoxy-L-scyllo-inosose + phosphate

For diagram of reaction click here and mechanism click here.

Other name(s): btrC (gene name); neoC (gene name); kanC (gene name)

Systematic name: D-glucose-6-phosphate phosphate-lyase (2-deoxy-scyllo-inosose-forming)

Comments: Requires Co²⁺ [2]. Involved in the biosynthetic pathways of several clinically important aminocyclitol antibiotics, including kanamycin, butirosin, neomycin and ribostamycin. Requires an NAD⁺ cofactor, which is transiently reduced during the reaction [1,4]. The enzyme from the bacterium Bacillus circulans forms a complex with the glutamine amidotransferase subunit of pyridoxal 5'-phosphate synthase (EC 4.3.3.6), which appears to stabilize the complex [6,7].

References:

1. Kudo, F., Yamauchi, N., Suzuki, R. and Kakinuma, K. Kinetic isotope effect and reaction mechanism of 2-deoxy-scyllo-inosose synthase derived from butirosin-producing Bacillus circulans. J. Antibiot. (Tokyo) 50 (1997) 424-428. [PMID: 9207913]

2. Kudo, F., Hosomi, Y., Tamegai, H. and Kakinuma, K. Purification and characterization of 2-deoxy-scyllo-inosose synthase derived from Bacillus circulans. A crucial carbocyclization enzyme in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics. J. Antibiot. (Tokyo) 52 (1999) 81-88. [PMID: 10344560]

3. Kudo, F., Tamegai, H., Fujiwara, T., Tagami, U., Hirayama, K. and Kakinuma, K. Molecular cloning of the gene for the key carbocycle-forming enzyme in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics and its comparison with dehydroquinate synthase. J. Antibiot. (Tokyo) 52 (1999) 559-571. [PMID: 10470681]

4. Huang, Z., Kakinuma, K. and Eguchi, T. Stereospecificity of hydride transfer in NAD⁺-catalyzed 2-deoxy-scyllo-inosose synthase, the key enzyme in the biosynthesis of 2-deoxystreptamine-containing aminocyclitol antibiotics. Bioorg. Chem. 33 (2005) 82-89. [PMID: 15788164]

5. Thuy, M.L., Kharel, M.K., Lamichhane, R., Lee, H.C., Suh, J.W., Liou, K. and Sohng, J.K. Expression of 2-deoxy-scyllo-inosose synthase (kanA) from kanamycin gene cluster in Streptomyces lividans. Biotechnol. Lett. 27 (2005) 465-470. [PMID: 15928851]

6. Tamegai, H., Nango, E., Koike-Takeshita, A., Kudo, F. and Kakinuma, K. Significance of the 20-kDa subunit of heterodimeric 2-deoxy-scyllo-inosose synthase for the biosynthesis of butirosin antibiotics in Bacillus circulans. Biosci. Biotechnol. Biochem. 66 (2002) 1538-1545. [PMID: 12224638]

7. Tamegai, H., Sawada, H., Nango, E., Aoki, R., Hirakawa, H., Iino, T. and Eguchi, T. Roles of a 20 kDa protein associated with a carbocycle-forming enzyme involved in aminoglycoside biosynthesis in primary and secondary metabolism. Biosci. Biotechnol. Biochem. 74 (2010) 1215-1219. [PMID: 20530911]

EC 4.2.3.125

Accepted name: α-muurolene synthase

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

For diagram of reaction click here.

Other name(s): Cop3

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

Comments: The enzyme has been characterized from the fungus Coprinus cinereus. Also gives germacrene A and γ-muurolene, see EC 4.2.3.23, germacrene-A synthase and EC 4.2.3.126, γ-muurolene synthase.

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

EC 4.2.3.126

Accepted name: γ-muurolene synthase

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

For diagram of reaction click here.

Glossary: γ-muurolene = (1S,4aS,8aR)-1-isopropyl-7-methyl-4-methylene-1,2,3,4,4a,5,6,8a-octahydronaphthalene

Other name(s): Cop3

Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lase (cyclizing, γ-muurolene-forming)

Comments: The enzyme has been characterized from the fungus Coprinus cinereus. Also gives germacrene A and α-muurolene, see EC 4.2.3.23, germacrene-A synthase and EC 4.2.3.125, α-muurolene synthase.

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

EC 4.2.3.127

Accepted name: β-copaene synthase

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

For diagram of reaction click here.

Other name(s): cop4

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

Comments: Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-δ-cadinene, β-cubebene, (+)-sativene and traces of several other sequiterpenoids [1-3]. β-Copaene is formed in the presence of Mg²⁺ but not Mn²⁺ [2]. See EC 4.2.3.13, (+)-δ-cadinene synthase, EC 4.2.3.128, β-cubebene synthase, and EC 4.2.3.129, (+)-sativene synthase.

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11 (2010) 1093-1106. [PMID: 20419721]

3. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

EC 4.2.3.128

Accepted name: β-cubebene synthase

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

For diagram of reaction click here.

Other name(s): cop4; Mg25

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

Comments: Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-δ-cadinene, β-copaene, (+)-sativene and traces of several other sequiterpenoids [2-4]. It is found in many higher plants such as Magnolia grandiflora (Southern Magnolia) together with germacrene A [1]. See EC 4.2.3.13, (+)-δ-cadinene synthase, EC 4.2.3.127, β-copaene synthase, EC 4.2.3.129, (+)-sativene synthase, and EC 4.2.3.23, germacrene A synthase.

References:

1. Lee, S. and Chappell, J. Biochemical and genomic characterization of terpene synthases in Magnolia grandiflora. Plant Physiol. 147 (2008) 1017-1033. [PMID: 18467455]

2. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

3. Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11 (2010) 1093-1106. [PMID: 20419721]

4. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

EC 4.2.3.129

Accepted name: (+)-sativene synthase

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

For diagram of reaction click here.

Other name(s): cop4

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

Comments: Isolated from the fungus Coprinus cinereus. The enzyme also forms (+)-δ-cadinene, β-copaene, β-cubebene, and traces of several other sequiterpenoids. See EC 4.2.3.13, (+)-δ-cadinene synthase, EC 4.2.3.127, β-copaene synthase, and EC 4.2.3.128, β-cubebene synthase.

References:

1. Agger, S., Lopez-Gallego, F. and Schmidt-Dannert, C. Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72 (2009) 1181-1195. [PMID: 19400802]

2. Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. Chembiochem. 11 (2010) 1093-1106. [PMID: 20419721]

3. Lopez-Gallego, F., Wawrzyn, G.T. and Schmidt-Dannert, C. Selectivity of fungal sesquiterpene synthases: role of the active site's H-1α loop in catalysis. Appl. Environ. Microbiol. 76 (2010) 7723-7733. [PMID: 20889795]

EC 4.2.3.130

Accepted name: tetraprenyl-β-curcumene synthase

Reaction: all-trans-heptaprenyl diphosphate = tetraprenyl-β-curcumene + diphosphate

For diagram of reaction click here.

Other name(s): ytpB (gene name)

Systematic name: all-trans-heptaprenyl-diphosphate diphosphate-lyase (cyclizing, tetraprenyl-β-curcumene-forming)

Comments: Isolated from Bacillus subtilis. This sesquarterpene is present in a number of Bacillus species.

References:

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

EC 4.3.99.3

Accepted name: 7-carboxy-7-deazaguanine synthase

Reaction: 6-carboxy-5,6,7,8-tetrahydropterin = 7-carboxy-7-carbaguanine + NH₃

For diagram of reaction click here.

Glossary: 7-carboxy-7-carbaguanine = 7-carboxy-7-deazaguanine

Other name(s): 7-carboxy-7-carbaguanine synthase; queE (gene name)

Systematic name: 6-carboxy-5,6,7,8-tetrahydropterin ammonia-lyase

Comments: The enzyme is a member of the superfamily of S-adenosyl-L-methionine-dependent radical (radical AdoMet) enzymes. Binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The reaction is part of the biosynthesis pathway of queuosine.

References:

1. McCarty, R.M., Somogyi, A., Lin, G., Jacobsen, N.E. and Bandarian, V. The deazapurine biosynthetic pathway revealed: in vitro enzymatic synthesis of preQ₀ from guanosine 5'-triphosphate in four steps. Biochemistry 48 (2009) 3847-3852. [PMID: 19354300]

[EC 5.5.1.21 copal-8-ol diphosphate synthase. This enzyme was misclassified at the public-review stage and so was withdrawn. See EC 4.2.1.133, copal-8-ol diphosphate hydratase. (EC 5.5.1.21 created 2012, deleted 2012)]

EC 6.2.1.38

Accepted name: (2,2,3-trimethyl-5-oxocyclopent-3-enyl)acetyl-CoA synthase

Reaction: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate + ATP + CoA = AMP + diphosphate + [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetyl-CoA

For diagram of reaction click here.

Other name(s): 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetyl-CoA synthetase

Systematic name: [(1R)-2,2,3-trimethyl-5-oxocyclopent-3-enyl]acetate:CoA ligase (AMP-forming)

Comments: Isolated from Pseudomonas putida. Forms part of the pathway of camphor catabolism.

References:

1. Ougham, H.J., Taylor, D.G. and Trudgill, P.W. Camphor revisited: involvement of a unique monooxygenase in metabolism of 2-oxo-Δ³-4,5,5-trimethylcyclopentenylacetic acid by Pseudomonas putida. J. Bacteriol. 153 (1983) 140-152. [PMID: 6848481]