An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: polyprenol dehydrogenase [NAD(P)H]
Reaction: (1) a ditrans,polycis-polyprenol + NAD(P)+ = a ditrans,polycis-polyprenal + NAD(P)H + H+
(2) a dolichol + NAD(P)+ = a dolichal + NAD(P)H + H+
Other name(s): dolichal reductase; DHRSX (gene name)
Systematic name: ditrans,polycis-polyprenol:NAD(P)+ oxidoreductase
Comments: The enzyme, present in all eukaryotes, catalyses the dehydrogenation of ditrans,polycis-polyprenol and the reduction of dolichal as part of the pathway that converts ditrans,polycis-polyprenol to dolichol (cf. EC 1.3.1.94, polyprenal reductase). The enzyme works equally well with NAD+ and NADP+, but due to the cellular ratios of NAD+/NADH and NADP+/NADPH, the enzyme catalyses the oxidation of of polyprenol using NAD+ as the electron acceptor, and the reduction of dolichal using NADPH as the electron donor.
References:
1. Wilson, M.P., Kentache, T., Althoff, C.R., Schulz, C., de Bettignies, G., Mateu Cabrera, G., Cimbalistiene, L., Burnyte, B., Yoon, G., Costain, G., Vuillaumier-Barrot, S., Cheillan, D., Rymen, D., Rychtarova, L., Hansikova, H., Bury, M., Dewulf, J.P., Caligiore, F., Jaeken, J., Cantagrel, V., Van Schaftingen, E., Matthijs, G., Foulquier, F. and Bommer, G.T. A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. Cell (2024) . [PMID: 38821050]
Accepted name: 1,2-dihydrovomilenine 19,20-reductase
Reaction: 17-O-acetylnorajmaline + NADP+ = (2R)-1,2-dihydrovomilenine + NADPH + H+
For diagram of reaction, click here
Other name(s): 1,2-dihydrovomilenine reductase; DHVR; RR4 (gene name); 17-O-acetylnorajmaline:NADP+ oxidoreductase
Systematic name: 17-O-acetylnorajmaline:NADP+ 19,20-oxidoreductase
Comments: The enzyme, characterized from the plant Rauvolfia serpentina, participates in the ajmaline biosynthesis pathway. It has a much lower activity on vomilenine.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Gao, S., von Schumann, G. and Stöckigt, J. A newly-detected reductase from Rauvolfia closes a gap in the biosynthesis of the antiarrhythmic alkaloid ajmaline. Planta Med. 68 (2002) 906-911. [PMID: 12391554]
2. Guo, J., Gao, D., Lian, J. and Qu, Y. De novo biosynthesis of antiarrhythmic alkaloid ajmaline. Nat. Commun. 15 (2024) 457. [PMID: 38212296]
Accepted name: polyprenal reductase
Reaction: a dolichal + NADP+ = a ditrans,polycis-polyprenal + NADPH + H+
Other name(s): SRD5A3 (gene name); DFG10 (gene name); polyprenol reductase (incorrect); ditrans,polycis-dolichol:NADP+ 2,3-oxidoreductase (incorrect)
Systematic name: dolichal:NADP+ 2,3-oxidoreductase
Comments: The enzyme, isolated from human fetal brain tissue but present in all eukaryotes, catalyses the reduction of the terminal double bond next to the aldehyde group in ditrans,polycis-polyprenal, as part of the pathway that produces dolichol. In mammalian cells dolichols are predominantly 18-21 isoprene units in length.
Links to other databases: BRENDA, EXPASY, GENE, KEGG, MetaCyc, CAS registry number:
References:
1. Sagami, H., Kurisaki, A. and Ogura, K. Formation of dolichol from dehydrodolichol is catalyzed by NADPH-dependent reductase localized in microsomes of rat liver. J. Biol. Chem. 268 (1993) 10109-10113. [PMID: 8486680]
2. Cantagrel, V., Lefeber, D.J., Ng, B.G., Guan, Z., Silhavy, J.L., Bielas, S.L., Lehle, L., Hombauer, H., Adamowicz, M., Swiezewska, E., De Brouwer, A.P., Blumel, P., Sykut-Cegielska, J., Houliston, S., Swistun, D., Ali, B.R., Dobyns, W.B., Babovic-Vuksanovic, D., van Bokhoven, H., Wevers, R.A., Raetz, C.R., Freeze, H.H., Morava, E., Al-Gazali, L. and Gleeson, J.G. SRD5A3 is required for converting polyprenol to dolichol and is mutated in a congenital glycosylation disorder. Cell 142 (2010) 203-217. [PMID: 20637498]
3. Wilson, M.P., Kentache, T., Althoff, C.R., Schulz, C., de Bettignies, G., Mateu Cabrera, G., Cimbalistiene, L., Burnyte, B., Yoon, G., Costain, G., Vuillaumier-Barrot, S., Cheillan, D., Rymen, D., Rychtarova, L., Hansikova, H., Bury, M., Dewulf, J.P., Caligiore, F., Jaeken, J., Cantagrel, V., Van Schaftingen, E., Matthijs, G., Foulquier, F. and Bommer, G.T. A pseudoautosomal glycosylation disorder prompts the revision of dolichol biosynthesis. Cell (2024) . [PMID: 38821050]
[EC 1.3.1.127 Deleted entry: vomilenine 19,20-reductase, now classified under EC 1.3.1.73, 1,2-dihydrovomilenine 19,20-reductase (EC 1.3.1.127 created 2024, deleted 2024)]
Accepted name: vomilenine reductase
Reaction: (2R)-1,2-dihydrovomilenine + NADP+ = vomilenine + NADPH + H+
For diagram of reaction, click here
Other name(s): VR (gene name); 1,2-dihydrovomilenine:NADP+ oxidoreductase
Systematic name: (2R)-1,2-dihydrovomilenine:NADP+ oxidoreductase
Comments: The enzyme, characterized from the plant Rauvolfia serpentina, participates in the ajmaline biosynthesis pathway.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 462127-03-3
References:
1. von Schumann, G., Gao, S. and Stöckigt, J. Vomilenine reductase - a novel enzyme catalyzing a crucial step in the biosynthesis of the therapeutically applied antiarrhythmic alkaloid ajmaline. J. Bioorg. Med. Chem. 10 (2002) 1913-1918. [PMID: 11937349]
2. Guo, J., Gao, D., Lian, J. and Qu, Y. De novo biosynthesis of antiarrhythmic alkaloid ajmaline. Nat. Commun. 15 (2024) 457. [PMID: 38212296]
Accepted name: 18-hydroxynorfluorocurarine reductase
Reaction: 17,18-epoxy-17-hydroxycur-19-ene + NADP+ = 18-hydroxynorfluorocurarine + NADPH + H+
For diagram of reaction click here
Glossary: 17,18-epoxy-17-hydroxycur-19-ene = (19E)-18-hydroxycur-19-en-17-al = Wieland-Gumlich aldehyde
norfluorocurarine = (19E)-cura-2(16),19-dien-17-al
Other name(s): Wieland-Gumlich aldehyde synthase
Systematic name: 17,18-epoxy-17-hydroxycur-19-ene:NADP+ oxidoreductase
Comments: The enzyme, isolated from the tree Strychnos nux-vomica, participates in the biosynthesis of strychnine. It belongs to the family of medium-chain dehydrogenase/reductases (MDRs). The enzyme forms an aldehyde group at C16, which results in spontaneous cyclization. In vitro the enzyme can also act on norfluorocurarine, but more slowly.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: 2-(methylaminoethyl)phosphonate dehydrogenase (acceptor)
Reaction: 2-(methylaminoethyl)phosphonate + acceptor + H2O = phosphonoacetaldehyde + methylamine + reduced acceptor
Other name(s): pbfC (gene name); N-methyl-2-aminoethylphosphonate dehydrogenase (acceptor)
Systematic name: 2-(methylaminoethyl)phosphonate:acceptor oxidoreductase (phosphonoacetaldehyde-forming)
Comments: Contains FAD. The enzyme from the bacterium Azospirillum sp. B510 reacts about tenfold less efficiently with 2-(ethylaminoethyl)phosphonate and about 400-fold less efficiently with (2-aminoethyl)phosphonate. Oxygen is used poorly as an electron acceptor (at least 50-fold less efficiently than the artificial acceptor DCPIP). The physiological electron acceptor is unknown.
References:
1. Zangelmi, E., Ruffolo, F., Dinhof, T., Gerdol, M., Malatesta, M., Chin, J.P., Rivetti, C., Secchi, A., Pallitsch, K. and Peracchi, A. Deciphering the role of recurrent FAD-dependent enzymes in bacterial phosphonate catabolism. iScience 26 (2023) 108108. [PMID: 37876809]
Accepted name: 2-oxoethane-1-sulfonamide synthase
Reaction: L-cysteine + 2 O2 = 2-oxoethane-1-sulfonamide + CO2 + H2O (overall reaction)
(1a) L-cysteine + O2 = (Z)-(2-aminovinyl)sulfanolate + CO2 + H2O
(1b) (Z)-(2-aminovinyl)sulfanolate + O2 = (Z)-2-aminoethene-1-sulfonate
(1c) (Z)-2-aminoethene-1-sulfonate + H2O = 2-oxoethane-1-sulfonamide + H2O
Glossary: 2-oxoethane-1-sulfonamide = 2-sulfamoylacetaldehyde
Other name(s): sbzM (gene name)
Systematic name: L-cysteine:oxygen oxidoreductase (2-oxoethane-1-sulfonamide-forming)
Comments: The enzyme, characterized from the bacterium Streptomyces sp. NCIMB40513, is a cupin dioxygenase that participates in the biosynthesis of the monoterpene alkaloids altemicidin, SB-203207 and SB-203208. The enzyme catalyses a complex transformation: it first catalyses a monooxygenation of the sulfur atom, which results in decarboxylation and formation of (Z)-(2-aminovinyl)sulfanolate. This is followed by a dioxygenation of the sulfur atom, forming (Z)-2-aminoethene-1-sulfonate. The resulting compound is unstable and undergoes an intramolecular rearrangement in which the amino group moves onto the oxidized sulfur atom, displacing an oxygen atom in the form of a water molecule and forming an SN bond. Another water molecule (not shown in the overall reaction) donates an oxygen atom that replaces the nitrogen at the other end of the molecule.
References:
1. Hu, Z., Awakawa, T., Ma, Z. and Abe, I. Aminoacyl sulfonamide assembly in SB-203208 biosynthesis. Nat. Commun. 10 (2019) 184. [PMID: 30643149]
Accepted name: 3-demethoxyubiquinone 3-hydroxylase (NADH)
Reaction: 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone + NADH + O2 = 3-demethylubiquinone-n + NAD+ + H2O
For diagram of reaction click here
Other name(s): COQ7
Systematic name: 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzoquinone,NADH:oxygen oxidoreductase (5-hydroxylating)
Comments: The enzyme, found in eukaryotes, is involved in the biosynthesis of ubiquinone. The vertebrate enzyme has no activity with 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzene-1,4-diol (cf. EC 1.14.99.60, 3-demethoxyubiquinol 3-hydroxylase). The number of isoprenoid subunits in the side chain varies in different species. The enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency.
References:
1. Lu, T.T., Lee, S.J., Apfel, U.P. and Lippard, S.J. Aging-associated enzyme human clock-1: substrate-mediated reduction of the diiron center for 5-demethoxyubiquinone hydroxylation. Biochemistry 52 (2013) 2236-2244. [PMID: 23445365]
2. Nicoll, C.R., Alvigini, L., Gottinger, A., Cecchini, D., Mannucci, B., Corana, F., Mascotti, M.L. and Mattevi, A. In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. Nat. Catal. 7 (2024) 148-160. [PMID: 38425362]
Accepted name: norfluorocurarine 18-hydroxylase
Reaction: norfluorocurarine + [reduced NADPH—hemoprotein reductase] + O2 = 18-hydroxynorfluorocurarine + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
Glossary: norfluorocurarine = (19E)-cura-2(16),19-dien-17-al
Other name(s): norfluorocurarine oxidase; CYP71A144
Systematic name: (19E)-cura-2(16),19-dien-17-al,[NADPH—hemoprotein reductase]:oxygen oxidoreductase (18-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme, isolated from the tree Strychnos nux-vomica, participates in the biosynthesis of strychnine.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: strychnine 10-hydroxylase
Reaction: strychnine + [reduced NADPH—hemoprotein reductase] + O2 = 10-hydroxystrychnine + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
For diagram of reaction click here
Glossary: strychnine = strychnidin-10-one
10-hydroxystrychnine (ref 1)| = 2-hydroxystrychnidin-10-one
Other name(s): CYP82D36
Systematic name: strychnine,[NADPH—hemoprotein reductase]:oxygen oxidoreductase (10-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme, isolated from the tree Strychnos nux-vomica, participates in the biosynthesis of brucine.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: β-colubrine 11-hydroxylase
Reaction: β-colubrine + [reduced NADPH—hemoprotein reductase] + O2 = 11-demethylbrucine + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
Glossary: β-colubrine = 2-methoxystrychnidine (IUPAC) = 10-methoxystrychnidine (ref 1)
11-demethylbrucine (ref 1) = 3-hydroxy-2-methoxystrichnidine (IUPAC)
Other name(s): CYP71AH44
Systematic name: β-colubrine,[NADPH—hemoprotein reductase]:oxygen oxidoreductase (11-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein. The enzyme, isolated from the tree Strychnos nux-vomica, participates in the biosynthesis of brucine.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: L-tryptophan 4-nitrase
Reaction: L-tryptophan + nitric oxide + O2 + reduced ferredoxin + H+ = 4-nitro-L-tryptophan + H2O + oxidized ferredoxin
Other name(s): txtE (gene name); 4-nitro-L-tryptophane synthase
Systematic name: L-tryptophan,nitric oxide, reduced ferredoxin:oxygen oxidoreductase (4-nitro-L-tryptophan-forming)
Comments: A cytochrome P-450 enzyme characterized from the bacterium Streptomyces turgidiscabies. The enzyme participates in biosynthesis of thaxtomins, cyclic dipeptides formed from the condensation of 4-nitro-L-tryptophan and L-phenylalanine that have phytotoxic properties. The enzyme requires ferredoxin as its electron donor and catalyses a reaction in which nitric oxide is oxidized to a nitro group and inserted into L-tryptophan at the 4 position (not necessarily in this order).
References:
1. Barry, S.M., Kers, J.A., Johnson, E.G., Song, L., Aston, P.R., Patel, B., Krasnoff, S.B., Crane, B.R., Gibson, D.M., Loria, R. and Challis, G.L. Cytochrome P450-catalyzed L-tryptophan nitration in thaxtomin phytotoxin biosynthesis. Nat. Chem. Biol. 8 (2012) 814-816. [PMID: 22941045]
Accepted name: L-tyrosine 3-nitrase
Reaction: L-tyrosine + nitric oxide + O2 + reduced ferredoxin + H+ = 3-nitro-L-tyrosine + H2O + oxidized ferredoxin
Other name(s): rufO (gene name); 3-nitro-tyrosine synthase
Systematic name: L-tyrosine,nitric oxide, reduced ferredoxin:oxygen oxidoreductase (3-nitro-L-tyrosine-forming)
Comments: A cytochrome P-450 enzyme characterized from the bacterium Streptomyces atratus. The enzyme participates in biosynthesis of rufomycins, circular heptapeptides with anti-mycobacterial activity. The enzyme requires ferredoxin as its electron donor and catalyses a reaction in which nitric oxide is oxidized to a nitro group and inserted into L-tyrosine at the 3 position (not necessarily in this order).
References:
1. Tomita, H., Katsuyama, Y., Minami, H. and Ohnishi, Y. Identification and characterization of a bacterial cytochrome P450 monooxygenase catalyzing the 3-nitration of tyrosine in rufomycin biosynthesis. J. Biol. Chem. 292 (2017) 15859-15869. [PMID: 28774961]
Accepted name: nocardicin C N-oxygenase
Reaction: nocardicin C + 2 O2 + 4 reduced ferredoxin + 4 H+ = nocardicin A + 3 H2O + 4 oxidized ferredoxin (overall reaction)
(1a) nocardicin C + O2 + 2 reduced ferredoxin + 2 H+ = 2'-N-hydroxynocardicin C + H2O + 2 oxidized ferredoxin
(1b) 2'-N-hydroxynocardicin C + O2 + 2 reduced ferredoxin + 2 H+ = 2'-N,N-dihydroxynocardicin C + 2 oxidized ferredoxin
(1c) 2'-N,N-dihydroxynocardicin C = nocardicin A + H2O
For diagram of reaction click here
Glossary: nocardicin C = (2R)-2-amino-4-{4-[(R)-amino({[(3S)-1-[(R)-carboxy(4-hydroxyphenyl)methyl]-2-oxoazetidin-3-yl]carbamoyl})methyl]phenoxy}butanoate
nocardicin A = (2R)-2-amino-4-{4-[(1Z)-{[(3S)-1-[(R)-carboxy(4-hydroxyphenyl)methyl]-2-oxoazetidin-3-yl]carbamoyl}(hydroxyimino)methyl]phenoxy}butanoate
Other name(s): nocL (gene name)
Systematic name: nocardicin C,reduced ferredoxin:O2 oxidoreductase (nocardicin A-forming)
Comments: This cytochrome P-450 enzyme, characterized from the bacterium Nocardia uniformis, is involved in the biosynthesis of the monolactam antibiotic nocardicin A.
References:
1. Kelly, W.L. and Townsend, C.A. Role of the cytochrome P450 NocL in nocardicin A biosynthesis. J. Am. Chem. Soc. 124 (2002) 8186-8187. [PMID: 12105888]
2. Kelly, W.L. and Townsend, C.A. Mutational analysis of nocK and nocL in the nocardicin a producer Nocardia uniformis. J. Bacteriol. 187 (2005) 739-746. [PMID: 15629944]
Accepted name: 3-dehydro-2,22-dideoxyecdysone 22-hydroxylase
Reaction: 3-dehydro-2,22-dideoxyecdysone + O2 + 2 reduced adrenodoxin + 2 H+ = 3-dehydro-2-deoxyecdysone + H2O + 2 oxidized adrenodoxin
Other name(s): CYP302A1; Disembodied; dib (gene name)
Systematic name: 3-dehydro-2,22-dideoxyecdysone,reduced adrenodoxin:oxygen oxidoreductase (22-hydroxylating)
Comments: This cytochrome P-450 monooxygenase catalyses the second of three sequential hydroxylation reactions that occur during the biosynthesis of 20-hydroxyecdysone, the major molting hormone of arthropods. The enzyme also acts on 3-dehydro-2,22,25-deoxyecdysone and 2,22-dideoxyecdysone.
References:
1. Rewitz, K.F., Rybczynski, R., Warren, J.T. and Gilbert, L.I. Identification, characterization and developmental expression of Halloween genes encoding P450 enzymes mediating ecdysone biosynthesis in the tobacco hornworm, Manduca sexta. Insect Biochem. Mol. Biol. 36 (2006) 188-199. [PMID: 16503480]
2. Rewitz, K.F., O'Connor, M.B. and Gilbert, L.I. Molecular evolution of the insect Halloween family of cytochrome P450s: phylogeny, gene organization and functional conservation. Insect Biochem. Mol. Biol. 37 (2007) 741-753. [PMID: 17628274]
Accepted name: 4-hydroxy-3-polyprenylbenzoate 5-hydroxylase
Reaction: 4-hydroxy-3-all-trans-polyprenylbenzoate + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + 2 H+ = 3,4-dihydroxy-5-all-trans-polyprenylbenzoate + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O
For diagram of reaction click here
Other name(s): COQ6 (ambiguous)
Systematic name: 4-hydroxy-3-all-trans-polyprenylbenzoate,ferredoxin:oxygen oxidoreductase (5-hydroxylating)
Comments: The enzyme, found in eukaryotes, is involved in the biosynthesis of ubiquinone. The vertebrate enzyme catalyses two hydroxylations in the pathway at the positions meta to the prenyl side chain (the other hydroxylation is classified as EC 1.14.15.46, 2-methoxy-6-polyprenylphenol 4-hydroxylase). The number of isoprenoid subunits in the side chain varies in different species. The enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency.
References:
1. Nicoll, C.R., Alvigini, L., Gottinger, A., Cecchini, D., Mannucci, B., Corana, F., Mascotti, M.L. and Mattevi, A. In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. Nat. Catal. 7 (2024) 148-160. [PMID: 38425362]
Accepted name: 2-methoxy-6-polyprenylphenol 4-hydroxylase
Reaction: 2-methoxy-6-(all-trans-polyprenyl)phenol + 2 reduced [2Fe-2S]-[ferredoxin] + O2 + 2 H+ = 2-methoxy-6-all-trans-polyprenyl-1,4-benzoquinol + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O
For diagram of reaction click here
Other name(s): COQ6 (ambiguous)
Systematic name: 2-methoxy-6-(all-trans-polyprenyl)phenol,ferredoxin:oxygen oxidoreductase (4-hydroxylating)
Comments: The enzyme, found in eukaryotes, is involved in the biosynthesis of ubiquinone. The vertebrate enzyme catalyses two hydroxylations in the pathway at the positions meta to the prenyl side chain (the other hydroxylation is classified as EC 1.14.15.45, 4-hydroxy-3-polyprenylbenzoate 5-hydroxylase). The number of isoprenoid subunits in the side chain varies in different species. The enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency.
References:
1. Nicoll, C.R., Alvigini, L., Gottinger, A., Cecchini, D., Mannucci, B., Corana, F., Mascotti, M.L. and Mattevi, A. In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. Nat. Catal. 7 (2024) 148-160. [PMID: 38425362]
Accepted name: 4α,5β-5,20-epoxytax-11-ene-4,9-diol 9-dehydrogenase
Reaction: 4α,5β-5,20-epoxytax-11-ene-4,9-diol + 2-oxoglutarate + O2 = 4-hydroxy-4α,5β-5,20-epoxytax-11-en-9-one + succinate + CO2 + H2O
Other name(s): T9α oxidase
Systematic name: 4α,5β-5,20-epoxytax-11-ene-4,9-diol,2-oxoglutarate:oxygen 9-oxidoreductase
Comments: The enzyme is active in the biosynthetic pathway of paclitaxel (Taxol) in Taxus species (yew).
References:
1. Zhang, Y., Wiese, L., Fang, H., Alseekh, S., Perez de Souza, L., Scossa, F., Molloy, J., Christmann, M. and Fernie, A.R. Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis. Mol. Plant 16 (2023) 1951-1961. [PMID: 37897038]
Accepted name: 3-demethoxyubiquinol 3-hydroxylase
Reaction: 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzene-1,4-diol + a reduced acceptor + O2 = 3-demethylubiquinol + acceptor + H2O
For diagram of reaction click here
Glossary: 3-demethylubiquinol = 3-methoxy-6-methyl-5-(all trans-polyprenyl)benzene-1,2,4-triol
Other name(s): 6-methoxy-3-methyl-2-(all-trans-polyprenyl)-1,4-benzoquinol 5-hydroxylase; COQ7 (gene name); clk-1 (gene name); ubiF (gene name); 6-methoxy-3-methyl-2-(all-trans-polyprenyl)-1,4-benzoquinol,acceptor:oxygen oxidoreductase (5-hydroxylating)
Systematic name: 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzene-1,4-diol,acceptor:oxygen oxidoreductase (5-hydroxylating)
Comments: This prokaryotic enzyme catalyses the last hydroxylation reaction during the biosynthesis of ubiquinone. The eukaryotic enzyme is classified under EC 1.14.13.253, 3-demethoxyubiquinone 3-hydroxylase (NADH).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Kwon, O., Kotsakis, A. and Meganathan, R. Ubiquinone (coenzyme Q) biosynthesis in Escherichia coli: identification of the ubiF gene. FEMS Microbiol. Lett. 186 (2000) 157-161. [PMID: 10802164]
Accepted name: 2-(all-trans-polyprenyl)phenol 6-hydroxylase (prephenate)
Reaction: (1) a 2-(all-trans-polyprenyl)phenol + prephenate + acceptor = a 3-(all-trans-polyprenyl)benzene-1,2-diol + 3-phenyl-2-oxopropanoate + CO2 + reduced acceptor
(2) a 2-methoxy-6-(all-trans-polyprenyl)phenol + prephenate + acceptor = a 2-methoxy-6-(all-trans-polyprenyl)benzene-1,4-diol + 3-phenyl-2-oxopropanoate + CO2 + reduced acceptor
(3) a 5-methoxy-2-methyl-3-(all-trans-polyprenyl)benzene-1,4-diol + prephenate + acceptor = a 3-demethylubiquinol + 3-phenyl-2-oxopropanoate + CO2 + reduced acceptor
For diagram of reaction click here
Glossary: 3-phenyl-2-oxopropanoate = phenylpyruvate
Other name(s): ubiquinone hydroxylase UbiUV
Systematic name: prephenate,acceptor:2-(all-trans-polyprenyl)phenol oxidoreductase (6-hydroxylating)
Comments: The enzyme, characterized from the bacterium Escherichia coli, catalyses three hydroxylation reactions in the oxygen-independent pathway for ubiquinone (UQ) biosynthesis. The reaction involves an electron acceptor whose identity remains unknown as of 2024. The Escherichia coli enzyme is a heterodimer, with both subunits containing a 4Fe-4S iron-sulfur cluster that is essential for activity and may serve as part of an electron transfer chain from the substrate to the unidentified electron acceptor.
References:
1. Pelosi, L., Vo, C.D., Abby, S.S., Loiseau, L., Rascalou, B., Hajj Chehade, M., Faivre, B., Gousse, M., Chenal, C., Touati, N., Binet, L., Cornu, D., Fyfe, C.D., Fontecave, M., Barras, F., Lombard, M. and Pierrel, F. Ubiquinone biosynthesis over the entire O2 range: Characterization of a conserved O2-independent pathway. mBio 10 (2019) . [PMID: 31289180]
2. Arias-Cartin, R., Kazemzadeh Ferizhendi, K., Sechet, E., Pelosi, L., Loeuillet, C., Pierrel, F., Barras, F. and Bouveret, E. Role of the Escherichia coli ubiquinone-synthesizing UbiUVT pathway in adaptation to changing respiratory conditions. mBio 14 (2023) e0329822. [PMID: 37283518]
3. Ferizhendi, K.K., Simon, P., Pelosi, L., Sechet, E., Arulanandam, R., Chehade, M.H., Rey, M., Onal, D., Flandrin, L., Chreim, R., Faivre, B., Vo, S.C., Arias-Cartin, R., Barras, F., Fontecave, M., Bouveret, E., Lombard, M. and Pierrel, F. An organic O donor for biological hydroxylation reactions. Proc. Natl. Acad. Sci. USA 121 (2024) e2321242121. [PMID: 38507448]
Accepted name: tryptophan 2-C-methyltransferase
Reaction: S-adenosyl-L-methionine + L-tryptophan = S-adenosyl-L-homocysteine + 2-methyl-L-tryptophan (overall reaction)
(1a) methylcob(III)alamin + L-tryptophan = cob(I)alamin + 2-methyl-L-tryptophan
(1b) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
Other name(s): tsrM (gene name); tryptophan 2-methyltransferase; S-adenosylmethionine:tryptophan 2-methyltransferase
Systematic name: S-adenosyl-L-methionine:L-tryptophan 2-C-methyltransferase
Comments: The enzyme, characterized from the bacterium Streptomyces laurentii, is involved in thiostrepton biosynthesis. It is a radical SAM enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. It has an exceptional reaction mechanism as the S-adenosyl-L-methionine (SAM) is not bound to the [4Fe-4S] center and does not produce a 5'-deoxyadenosyl radical but instead is believed to be involved in binding of the L-tryptophan substrate. After transfer of the methyl group from methylcob(III)alaminIn a methyl transfer from SAM to the generated cob(I)alamin takes place, preparing the enzyme for the next catalytic cycle. The original methyl group configuration is preserved.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 126626-83-3
References:
1. Frenzel, T., Zhou, P. and Floss, H.G. Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase. Arch. Biochem. Biophys. 278 (1990) 35-40. [PMID: 2321967]
2. Pierre, S., Guillot, A., Benjdia, A., Sandstrom, C., Langella, P. and Berteau, O. Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes. Nat. Chem. Biol. 8 (2012) 957-959. [PMID: 23064318]
3. Blaszczyk, A.J., Silakov, A., Zhang, B., Maiocco, S.J., Lanz, N.D., Kelly, W.L., Elliott, S.J., Krebs, C. and Booker, S.J. Spectroscopic and electrochemical characterization of the ion-sulfur and cobalamin cofactors of TsrM, an unusual radical S-adenosylmethionine methylase. J. Am. Chem. Soc. 138 (2016) 3416-3426. [PMID: 26841310]
4. Blaszczyk, A.J., Wang, B., Silakov, A., Ho, J.V. and Booker, S.J. Efficient methylation of C2 in L-tryptophan by the cobalamin-dependent radical S-adenosylmethionine methylase TsrM requires an unmodified N1 amine. J. Biol. Chem. 292 (2017) 15456-15467. [PMID: 28747433]
5. Knox, H.L., Chen, P.Y., Blaszczyk, A.J., Mukherjee, A., Grove, T.L., Schwalm, E.L., Wang, B., Drennan, C.L. and Booker, S.J. Structural basis for non-radical catalysis by TsrM, a radical SAM methylase. Nat. Chem. Biol. 17 (2021) 485-491. [PMID: 33462497]
Accepted name: cytidylyl-2-hydroxyethylphosphonate methyltransferase
Reaction: 2 S-adenosyl-L-methionine + cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + reduced acceptor = S-adenosyl-L-homocysteine + 5'-deoxyadenosine + L-methionine + cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) + oxidized acceptor (overall reaction)
(1a) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
(1b) methylcob(III)alamin + cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} + S-adenosyl-L-methionine = cob(III)alamin + cytidine 5'-({hydroxy[(S)-2-hydroxypropyl]phosphonoyl}phosphate) + 5'-deoxyadenosine + L-methionine
(1c) cob(III)alamin + reduced acceptor = cob(I)alamin + oxidized acceptor
Other name(s): Fom3; S-adenosyl-L-methionine:methylcob(III)alamin:2-hydroxyethylphosphonate methyltransferase (incorrect); 2-hydroxyethylphosphonate methyltransferase (incorrect)
Systematic name: S-adenosyl-L-methionine:cytidine 5'-{[hydroxy(2-hydroxyethyl)phosphonoyl]phosphate} C2-methyltransferase
Comments: Requires cobalamin. The enzyme, isolated from the bacterium Streptomyces wedmorensis, is involved in fosfomycin biosynthesis. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. The enzyme uses two molecues of SAM for the reaction. One molecule forms a 5'-deoxyadenosyl radical, while the other is used to methylate the cobalamin cofactor. The 5'-deoxyadenosyl radical abstracts a hydrogen from the C2 position of cytidine 5'-{[(2-hydroxyethyl)phosphonoyl]phosphate} forming a free radical that reacts with the methyl group on methylcob(III)alamin at the opposite side from SAM and the [4Fe-4S] cluster with inversion of configuration to produce the (S)-isomer of the methylated product and cob(II)alamin. Both the [4Fe-4S] cluster and the cob(II)alamin need to be reduced by an unknown factor(s) before the enzyme could catalyse another cycle.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Woodyer, R.D., Li, G., Zhao, H. and van der Donk, W.A. New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin. Chem. Commun. (Camb.) (2007) 359-361. [PMID: 17220970]
2. Allen, K.D. and Wang, S.C. Initial characterization of Fom3 from Streptomyces wedmorensis: The methyltransferase in fosfomycin biosynthesis. Arch. Biochem. Biophys. 543 (2014) 67-73. [PMID: 24370735]
3. Sato, S., Kudo, F., Kim, S.Y., Kuzuyama, T. and Eguchi, T. Methylcobalamin-dependent radical SAM C-methyltransferase Fom3 recognizes cytidylyl-2-hydroxyethylphosphonate and catalyzes the nonstereoselective C-methylation in fosfomycin biosynthesis. Biochemistry 56 (2017) 3519-3522. [PMID: 28678474]
4. Blaszczyk, A.J. and Booker, S.J. A (re)discovery of the Fom3 substrate. Biochemistry 57 (2018) 891-892. [PMID: 29345912]
5. Sato, S., Kudo, F., Kuzuyama, T., Hammerschmidt, F. and Eguchi, T. C-methylation catalyzed by Fom3, a cobalamin-dependent radical S-adenosyl-L-methionine enzyme in fosfomycin biosynthesis, proceeds with inversion of configuration. Biochemistry 57 (2018) 4963-4966. [PMID: 29966085]
Accepted name: N-acetyldemethylphosphinothricin P-methyltransferase
Reaction: 2 S-adenosyl-L-methionine + N-acetyldemethylphosphinothricin + reduced acceptor = S-adenosyl-L-homocysteine + 5'-deoxyadenosine + L-methionine + N-acetylphosphinothricin + oxidized acceptor (overall reaction)
(1a) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
(1b) methylcob(III)alamin + N-acetyldemethylphosphinothricin + S-adenosyl-L-methionine = cob(III)alamin + N-acetylphosphinothricin + 5'-deoxyadenosine + L-methionine
(1c) cob(III)alamin + reduced acceptor = cob(I)alamin + oxidized acceptor
Glossary: N-acetyldemethylphosphinothricin = (2S)-2-acetamido-4-phosphinatobutanoate
Other name(s): phpK (gene name); bcpD (gene name); P-methylase
Systematic name: S-adenosyl-L-methionine:N-acetyldemethylphosphinothricin P-methyltransferase
Comments: The enzyme was originally characterized from bacteria that produce the tripeptides bialaphos and phosalacine, which inhibit plant and bacterial glutamine synthetases. It is a radical S-adenosyl-L-methionine (SAM) enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. According to the proposed mechanism, the reduced iron-sulfur center donates an electron to SAM, resulting in homolytic cleavage of the carbon-sulfur bond to form a 5'-deoxyadenosyl radical that abstracts the hydrogen atom from the P-H bond of the substrate, forming a phosphinate-centered radical. This radical reacts with methylcob(III)alamin to produce the methylated product and cob(II)alamin, which is reduced by an unknown donor to cob(I)alamin. A potential route for restoring the latter back to methylcob(III)alamin is a nucleophilic attack on a second SAM molecule. The enzyme acts in vivo on N-acetyldemethylphosphinothricin-L-alanyl-L-alanine or N-acetyl-demethylphosphinothricin-L-alanyl-L-leucine, the intermediates in the biosynthesis of bialaphos and phosalacine, respectively. This transformation produces the only example of a carbon-phosphorus-carbon linkage known to occur in nature.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Kamigiri, K., Hidaka, T., Imai, S., Murakami, T. and Seto, H. Studies on the biosynthesis of bialaphos (SF-1293) 12. C-P bond formation mechanism of bialaphos: discovery of a P-methylation enzyme. J. Antibiot. (Tokyo) 45 (1992) 781-787. [PMID: 1624380]
2. Hidaka, T., Hidaka, M., Kuzuyama, T. and Seto, H. Sequence of a P-methyltransferase-encoding gene isolated from a bialaphos-producing Streptomyces hygroscopicus. Gene 158 (1995) 149-150. [PMID: 7789803]
3. Werner, W.J., Allen, K.D., Hu, K., Helms, G.L., Chen, B.S. and Wang, S.C. In vitro phosphinate methylation by PhpK from Kitasatospora phosalacinea. Biochemistry 50 (2011) 8986-8988. [PMID: 21950770]
4. Allen, K.D. and Wang, S.C. Spectroscopic characterization and mechanistic investigation of P-methyl transfer by a radical SAM enzyme from the marine bacterium Shewanella denitrificans OS217. Biochim. Biophys. Acta 1844 (2014) 2135-2144. [PMID: 25224746]
5. Hu, K., Werner, W.J., Allen, K.D. and Wang, S.C. Investigation of enzymatic C-P bond formation using multiple quantum HCP nuclear magnetic resonance spectroscopy. Magn. Reson. Chem. 53 (2015) 267-272. [PMID: 25594737]
Accepted name: 2-(S-pantetheinyl)-carbapenam-3-carboxylate methyltransferase
Reaction: (1) (2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 2 S-adenosyl-L-methionine + reduced acceptor = (2R,3R,5S,6R)-6-(methyl)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 5'-deoxyadenosine + L-methionine + S-adenosyl-L-homocysteine + oxidized acceptor (overall reaction)
(1a) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
(1b) methylcob(III)alamin + (2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + S-adenosyl-L-methionine = cob(III)alamin + (2R,3R,5S,6R)-6-(methyl)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 5'-deoxyadenosine + L-methionine
(1c) cob(III)alamin + reduced acceptor = cob(I)alamin + oxidized acceptor
(2) (2R,3R,5S,6R)-6-(methyl)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 2 S-adenosyl-L-methionine + reduced acceptor = (2R,3R,5S,6R)-6-(ethyl)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 5'-deoxyadenosine + L-methionine + S-adenosyl-L-homocysteine + oxidized acceptor (overall reaction)
(2a) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin
(2b) methylcob(III)alamin + (2R,3R,5S,6R)-6-(methyl)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + S-adenosyl-L-methionine = cob(III)alamin + (2R,3R,5S,6R)-6-(ethyl)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 5'-deoxyadenosine + L-methionine
(2c) cob(III)alamin + reduced acceptor = cob(I)alamin + oxidized acceptor
Other name(s): thnK (gene name)
Systematic name: S-adenosyl-L-methionine:(2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate 6-C-methyltransferase
Comments: A radical SAM (AdoMet) enzyme that catalyses two consecutive methylations during the biosynthesis of complex carbapenem antibiotics. The enzyme adds a methyl group at position 6, followed by a second methylation that converts the methyl group to an ethyl group. The enzyme binds a [4Fe-4S] cluster and requires a cobalamin cofactor and an electron donor. Methyl viologen can be used in vitro.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Marous, D.R., Lloyd, E.P., Buller, A.R., Moshos, K.A., Grove, T.L., Blaszczyk, A.J., Booker, S.J. and Townsend, C.A. Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis. Proc. Natl. Acad. Sci. USA 112 (2015) 10354-10358. [PMID: 26240322]
2. Sinner, E.K. and Townsend, C.A. Purification and characterization of sequential cobalamin-dependent radical SAM methylases ThnK and TokK in carbapenem β-lactam antibiotic biosynthesis. Methods Enzymol. 669 (2022) 29-44. [PMID: 35644176]
Accepted name: hydroxystrychnine O-methyltransferase
Reaction: S-adenosyl-L-methionine + 10-hydroxystrychnine = S-adenosyl-L-homocysteine + β-colubrine
For diagram of reaction click here
Glossary: β-colubrine = 2-methoxystrychnidin-10-one = (4aR,5aS,8aR,13aS,15aS,15bR)-10-methoxy-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one
10-hydroxystrychnine (ref 1) = 2-hydroxystrychnidin-10-one (IUPAC)
Systematic name: S-adenosyl-L-methionine:hydroxystrychnine O-methyltransferase
Comments: The enzyme, isolated from the tree Strychnos nux-vomica, participates in the biosynthesis of brucine. It can methylate 10-hydroxystrychnine, and, with lower efficiency, 11-hydroxystrychnine and 11-demethylbrucine.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: isoflavone 3'-O-methyltransferase
Reaction: S-adenosyl-L-methionine + a 3'-hydroxyisoflavone = S-adenosyl-L-homocysteine + a 3'-methoxyisoflavone
Other name(s): PlOMT4; OMT4; 3'-OMT
Systematic name: S-adenosyl-L-methionine:3'-hydroxyisoflavone 3'-O-methyltransferase
Comments: The enzyme catalyses a step in the biosynthesis of 3'-methoxypuerarin, an isoflavone with bioactive properties isolated from the roots of the leguminous plant Pueraria lobata var. leguminosa. The highest activity has been found for 3'-hydroxydaidzein. The enzyme has low activity on the 3'-hydroxyflavones luteolin and quercetin. 3'-hydroxypuerarin is not a substrate.
References:
1. Li, J., Li, C., Gou, J. and Zhang, Y. Molecular cloning and functional characterization of a novel isoflavone 3'-O-methyltransferase from Pueraria lobata. Front. Plant Sci. 7 (2016) 793. [PMID: 27458460]
Accepted name: resveratrol 4'-O-methyltransferase
Reaction: S-adenosyl-L-methionine + trans-resveratrol = S-adenosyl-L-homocysteine + 4'-O-methyl-trans-resveratrol
Other name(s): AcOMT1
Systematic name: S-adenosyl-L-methionine:trans-resveratrol 4'-O-methyltransferase
Comments: The enzyme occurs in the roots and leaves of the plant Acorus calamus (sweet flag). In additon to trans-reveratrol it is active toward isorhapontigenin and shows slight activities toward piceatannol, oxyresveratrol, and pinostilbene.
References:
1. Koeduka, T., Hatada, M., Suzuki, H., Suzuki, S. and Matsui, K. Molecular cloning and functional characterization of an O-methyltransferase catalyzing 4'-O-methylation of resveratrol in Acorus calamus. J. Biosci. Bioeng. 127 (2019) 539-543. [PMID: 30471982]
Accepted name: valine amidinotransferase
Reaction: L-arginine + L-valine = N-amidino-L-valine + L-ornithine
Other name(s): ktmE (gene name); st-amdT (gene name)
Systematic name: L-arginine:L-valine amidinotransferase
Comments: The enzyme, characterized from the bacterium Salinispora tropica, participates in the biosynthesis of ketomemicins. In vitro the enzyme could use multiple other amino acids, including L-cysteine, L-isoleucine, L-leucine, L-methionine, L-tyrosine, L-phenylalanine and L-tryptophan instead of L-valine.
References:
1. Ogasawara, Y., Fujimori, M., Kawata, J. and Dairi, T. Characterization of three amidinotransferases involved in the biosynthesis of ketomemicins. Bioorg. Med. Chem. Lett. 26 (2016) 3662-3664. [PMID: 27289319]
Accepted name: arginine amidinotransferase
Reaction: 2 L-arginine = Nα-amidino-L-arginine + L-ornithine
Other name(s): ktmE (gene name); st-amdT (gene name)
Systematic name: L-arginine:L-arginine amidinotransferase
Comments: The enzyme, characterized from the bacteria Micromonospora sp. ATCC 39149 and Streptomyces mobaraensis, participates in the biosynthesis of ketomemicins.
References:
1. Ogasawara, Y., Fujimori, M., Kawata, J. and Dairi, T. Characterization of three amidinotransferases involved in the biosynthesis of ketomemicins. Bioorg. Med. Chem. Lett. 26 (2016) 3662-3664. [PMID: 27289319]
Accepted name: N-acetylneuraminate 9-O-acetyltransferase
Reaction: acetyl-CoA + CMP-N-acetyl-β-neuraminate = CoA + CMP-N-acetyl-9-O-acetyl-β-neuraminate
Other name(s): N-acetylneuraminate 7(8)-O-acetyltransferase; sialate O-acetyltransferase; N-acetylneuraminate 7,8-O-acetyltransferase; acetyl-CoA:N-acetylneuraminate-7- or 8-O-acetyltransferase; acetyl-CoA:N-acetylneuraminate-7- and/or 8-O-acetyltransferase; glycoprotein 7(9)-O-acetyltransferase; acetyl-CoA:N-acetylneuraminate-9(7)-O-acetyltransferase; N-acetylneuraminate O7-(or O9-)acetyltransferase; acetyl-CoA:N-acetylneuraminate-9(or 7)-O-acetyltransferase; CASD1; acetyl-CoA:N-acetylneuraminate 7-O(or 9-O)-acetyltransferase; N-acetylneuraminate 7-O(or 9-O)-acetyltransferase
Systematic name: acetyl-CoA:CMP-N-acetyl-β-neuraminate 9-O-acetyltransferase
Comments: The enzyme, found in animals, is essential for the formation of acetylated sialoglycans. The acetyl group has been shown to spontaneously move between the 9-O, 8-O, and 7-O positions of the neuraminate, with 9-O acetylation being most favoured.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 9054-50-6
References:
1. Schauer, R. Biosynthese von N-Acetyl-O-acetylneuraminsaüren. I. Inkorporation von [14C]Acetate in Schnitte der Unterkieferspeicheldrüse von Rind und Pferd. Hoppe-Seyler's Z. Physiol. Chem. 351 (1970) 595-602. [PMID: 5446640]
2. Schauer, R. Biosynthese von N-Acetyl-O-acetylneuraminsaüren. II. Untersuchungen über Substrat und intracelluläre Lokalisation der Acetyl-coenzym A: N-acetylneuraminat-7- and 8-O-acetyltransferase von Rind. Hoppe-Seyler's Z. Physiol. Chem. 351 (1970) 749-758. [PMID: 5425947]
3. Baumann, A.M., Bakkers, M.J., Buettner, F.F., Hartmann, M., Grove, M., Langereis, M.A., de Groot, R.J. and Muhlenhoff, M. 9-O-Acetylation of sialic acids is catalysed by CASD1 via a covalent acetyl-enzyme intermediate. Nat. Commun. 6 (2015) 7673. [PMID: 26169044]
Accepted name: phosphorylated butenolide synthase
Reaction: a 3-oxoacyl-[acyl-carrier protein] + glycerone phosphate = a (4-alkanoyl-5-oxo-2H-furan-3-yl)methyl phosphate + H2O + a holo-[acyl-carrier protein] (overall reaction)
(1a) a 3-oxoacyl-[acyl-carrier protein] + glycerone phosphate = a 2-oxo-3-(phosphooxy)propyl 3-oxoalkanoate + a holo-[acyl-carrier protein]
(1b) a 2-oxo-3-(phosphooxy)propyl 3-oxoalkanoate = a (4-alkanoyl-5-oxo-2H-furan-3-yl)methyl phosphate + H2O (spontaneous)
Glossary: glycerone phosphate = dihydroxyacetone phosphate = 3-hydroxy-2-oxopropyl phosphate
Other name(s): 2-oxo-3-(phosphooxy)propyl 3-oxoalkanoate synthase; afsA (gene name); scbA (gene name); barX (gene name); mmfL (gene name)
Systematic name: 3-oxoacyl-[acyl-carrier protein]:glycerone phosphate 3-oxoacyltransferase
Comments: The enzyme catalyses the first committed step in the biosynthesis of γ-butyrolactone, as well as 2-alkyl-4-hydroxymethylfuran-3-carboxylate (methylenomycin furan) autoregulators that control secondary metabolism and morphological development in Streptomyces bacteria.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Horinouchi, S., Suzuki, H., Nishiyama, M. and Beppu, T. Nucleotide sequence and transcriptional analysis of the Streptomyces griseus gene (afsA) responsible for A-factor biosynthesis. J. Bacteriol. 171 (1989) 1206-1210. [PMID: 2492509]
2. Kato, J.Y., Funa, N., Watanabe, H., Ohnishi, Y. and Horinouchi, S. Biosynthesis of γ-butyrolactone autoregulators that switch on secondary metabolism and morphological development in Streptomyces. Proc. Natl. Acad. Sci. USA 104 (2007) 2378-2383. [PMID: 17277085]
3. Hsiao, N.H., Soding, J., Linke, D., Lange, C., Hertweck, C., Wohlleben, W. and Takano, E. ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize γ-butyrolactones. Microbiology 153 (2007) 1394-1404. [PMID: 17464053]
4. Lee, Y.J., Kitani, S. and Nihira, T. Null mutation analysis of an afsA-family gene, barX, that is involved in biosynthesis of the γ-butyrolactone autoregulator in Streptomyces virginiae. Microbiology 156 (2010) 206-210. [PMID: 19778967]
5. Corre, C., Haynes, S.W., Malet, N., Song, L. and Challis, G.L. A butenolide intermediate in methylenomycin furan biosynthesis is implied by incorporation of stereospecifically 13C-labelled glycerols. Chem. Commun. (Camb.) 46 (2010) 4079-4081. [PMID: 20358097]
6. Zhou, S., Malet, N.R., Song, L., Corre, C. and Challis, G.L. MmfL catalyses formation of a phosphorylated butenolide intermediate in methylenomycin furan biosynthesis. Chem. Commun. (Camb.) 56 (2020) 14443-14446. [PMID: 33146163]
Accepted name: chlorogenate caffeoyltransferase
Reaction: 2 chlorogenate = 3,5-dicaffeoylquinate + quinate
Other name(s): CCT (gene name)
Systematic name: chlorogenate:chlorogenate 3-O-caffeoyltransferase
Comments: The enzyme has been purified from Solanum lycopersicum (tomato) fruits. In the vacuole, at pH 4-5, it produces 3,5-dicaffeoylquinic acid from cholorgenic acid. In the cytoplasm, at pH 6-7, it can use aromatic acyl-CoAs as donors and catalyses the reaction of EC 2.3.1.99 (quinate O-hydroxycinnamoyltransferase). The initial product, 3,5-dicaffeoylquinic acid, undergoes spontaneous acyl migration to form 4,5-dicaffeoylquinic acid. Small amounts of 1,5-dicaffeoylquinic acid are formed as a byproduct.
References:
1. Moglia, A., Lanteri, S., Comino, C., Hill, L., Knevitt, D., Cagliero, C., Rubiolo, P., Bornemann, S. and Martin, C. Dual catalytic activity of hydroxycinnamoyl-coenzyme A quinate transferase from tomato allows it to moonlight in the synthesis of both mono- and dicaffeoylquinic acids. Plant Physiol. 166 (2014) 1777-1787. [PMID: 25301886]
Accepted name: 17,18-epoxy-17-hydroxycur-19-ene N-malonyltransferase
Reaction: malonyl-CoA + 17,18-epoxy-17-hydroxycur-19-ene = CoA + prestrychnine
For diagram of reaction click here
Glossary: 17,18-epoxy-17-hydroxycur-19-ene = (19E)-18-hydroxycur-19-en-17-al = Wieland-Gumlich aldehyde
prestrychnine = 3-(17,18-epoxy-17-hydroxycur-19-en-1-yl)-3-oxopropanoic acid
Other name(s): Wieland-Gumlich aldehyde N-malonyltransferase
Systematic name: malonyl-CoA:17,18-epoxy-17-hydroxycur-19-ene N-malonyltransferase
Comments: The enzyme, characterized from the tree Strychnos nux-vomica, catalyses the last step in the biosynthesis of strychnine. The product, prestrychnine, undergoes a slow spontaneous decarboxylation and cyclization, forming strychnine.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: 17,18-epoxy-17-hydroxycur-19-ene N-acetyltransferase
Reaction: acetyl-CoA + 17,18-epoxy-17-hydroxycur-19-ene = CoA + diaboline
For diagram of reaction click here
Glossary: 17,18-epoxy-17-hydroxycur-19-ene = (19E)-18-hydroxycur-19-en-17-al = Wieland-Gumlich aldehyde
diaboline = (17R)-acetyl-17,18-epoxy-17-hydroxycur-19-ene
Other name(s): Wieland-Gumlich aldehyde N-acetyltransferase
Systematic name: acetyl-CoA:17,18-epoxy-17-hydroxycur-19-ene N-acetyltransferase
Comments: The enzyme has been characterized from a nonstrychnine-producing Strychnos sp. (Strychnos potatorum).
References:
1. Singh, H., Kapoor, V.K., Phillipson, J.D. and Bisset, N.G. Diaboline from Strychnos potatorum. Phytochemistry 14 (1975) 587-588.
2. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: long-chain acyl-[acp]:L-phenylalanine N-acyltransferase
Reaction: 11-methyldodecanoyl-[acp] + L-phenylalanine = [acp] + N-(11-methyldodecanoyl)-L-phenylalanine
Other name(s): N-acyl amino acid synthase A; nasA (gene name)
Systematic name: long-chain acyl-[acp]:L-phenylalanine N-acyltransferase
Comments: The enzyme, characterized from an environmental DNA sample and expressed in Paraburkholderia graminis, catalyses the transfer of linear and branched long-chain acyl-[acp] molecules to L-phenylalanine, forming N-acyl-L-phenylalanine molecules.
References:
1. Craig, J.W., Chang, F.Y., Kim, J.H., Obiajulu, S.C. and Brady, S.F. Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse proteobacteria. Appl. Environ. Microbiol. 76 (2010) 1633-1641. [PMID: 20081001]
2. Craig, J.W. and Brady, S.F. Discovery of a metagenome-derived enzyme that produces branched-chain acyl-(acyl-carrier-protein)s from branched-chain α-keto acids. Chembiochem 12 (2011) 1849-1853. [PMID: 21714057]
Accepted name: branched-chain 2-oxoacid:malonyl-[acyl-carrier protein] acyltransferase
Reaction: 4-methyl-2-oxopentanoate + malonyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine = 5-methyl-3-oxohexanoyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + 2 CO2 (overall reaction)
(1a) 4-methyl-2-oxopentanoate + a [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine = -a [lipoyl-carrier protein]-N6-[(3-methyl-2-oxobutanoyl)-(R)-lipoyl]-L-lysine + CO2
(1b) a [lipoyl-carrier protein]-N6-[(3-methyl-2-oxobutanoyl)-(R)-lipoyl]-L-lysine + malonyl-[acp] = 5-methyl-3-oxohexanoyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine + CO2
Glossary: 4-methyl-2-oxopentanoate = 2-oxoisocaproate
Other name(s): nasB (gene name)
Systematic name: branched-chain 2-oxoacid:malonyl-[acyl-carrier protein] acyltransferase
Comments: The enzyme, characterized from an environmental DNA sample and expressed in Paraburkholderia graminis, is a complex enzyme whose purpose is to divert branched-chain 2-oxo acids to production of branched-chain N-acyl amino acids by producing branched 3-oxoacyl-[acp] molecules. NasB accepts branched-chain 2-oxoacids such as 4-methyl-2-oxopentanoate, and catalyses a decarboxylative transfer to a thiamine diphosphate cofactor, followed by a transfer to a lipoyl cofactor, and finally a second decarboxylative transfer to the malonyl-[acp] acceptor. The products, such as 5-methyl-3-oxohexanoyl-[acp], can be extended by the fatty acid synthase system to form branched long-chain fatty-acyl-[acp] molecules, which serve as substrates for EC 2.3.1.327, long-chain acyl-[acp]:L-phenylalanine N-acyltransferase (NasA). During the reaction the lipoyl cofactor is reduced to dihydrolipoyl, which must be oxidized back to lipoyl by an unknown enzyme.
References:
1. Craig, J.W. and Brady, S.F. Discovery of a metagenome-derived enzyme that produces branched-chain acyl-(acyl-carrier-protein)s from branched-chain α-keto acids. Chembiochem 12 (2011) 1849-1853. [PMID: 21714057]
Accepted name: (sulfonamide-N)(L-isoleucyl)altemidicin (3R)-3-methyl-L-phenylalanyltransferase
Reaction: (3R)-3-methyl-L-phenylalanyl-[peptidyl carrier-protein] + SB-203207 = [peptidyl carrier-protein] + SB-203208
Glossary: SB-203207 = (sulfonamide-N)(L-isoleucyl)altemidicin = 4-(aminocarbonyl)-7-[[(2-amino-3-methylpentanoyl)aminosul phonyl]acetamido]-2,4a,5,6,7,7a-hexahydro-6-hydroxy-2-methyl-1H-2- pyrindine-7-carboxylate
SB-203208 = 4-(aminocarbonyl)-7-[[(2-amino-3-methyl pentanoyl)-aminosulphonyl]acetamido]-2,4a,5,6,7,7a-hexahydro-6-(2- amino-3-phenylbutanoyl oxy)-2-methyl-1H-2-pyrindine-7-carboxylate
Other name(s): sbzC (gene name)
Systematic name: (3R)-3-methyl-L-phenylalanyl-[peptidyl carrier-protein]:SB-20307 O-(3R)-3-methyl-L-phenylalanyl-transferase
Comments: The enzyme, characterized from the bacterium Streptomyces sioyaensis, catalyses the last step in the biosynthesis of the monoterpene alkaloid SB-203208.
References:
1. Hu, Z., Awakawa, T., Ma, Z. and Abe, I. Aminoacyl sulfonamide assembly in SB-203208 biosynthesis. Nat. Commun. 10 (2019) 184. [PMID: 30643149]
Accepted name: altemicidin L-isoleucyltransferase
Reaction: L-isoleucyl-[tRNAIle] + altemicidin = [tRNAIle] + SB-203207
Glossary: altemicidin = (4aR,6S,7R,7aS)-4-carbamoyl-6-hydroxy-2-methyl-7-[(2-sulamoylacetyl)amino]-4a,5,6,7a-tetrahydro-1H-cyclopenta[c]pyridine-7-carboxylate
SB-203207 = (sulfonamide-N)(L-isoleucyl)altemidicin = 4-(aminocarbonyl)-7-[[(2-amino-3-methylpentanoyl)aminosulphonyl]acetamido]-2,4a,5,6,7,7a-hexahydro-6-hydroxy-2-methyl-1H-2- pyrindine-7-carboxylate
Other name(s): sbzA (gene name)
Systematic name: L-isoleucyl-[tRNAIle]:altemicidin L-isoleucyltransferase
Comments: The enzyme, isolated from the bacterium Streptomyces sp. NCIMB40513, catalyses the N-aminoacyl transfer of L-isoleucine from a charged isoleucine tRNA onto the primary sulfonamide group of the monoterpene alkaloid altemicidin.
References:
1. Hu, Z., Awakawa, T., Ma, Z. and Abe, I. Aminoacyl sulfonamide assembly in SB-203208 biosynthesis. Nat. Commun. 10 (2019) 184. [PMID: 30643149]
Accepted name: S-adenosyl-L-methionine:NAD+ aminocarboxypropyltransferase
Reaction: S-adenosyl-L-methionine + NAD+ = S-methyl-5'-thioadenosine + (4aR,7S)-2-(adenosyl(5')diphospho(5)ribosyl)-7-amino-4-carbamoyl-4a,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-7-carboxylate
Glossary: S-methyl-5'-thioadenosine = 5'-methylthioadenosine
Other name(s): sbzP (gene name)
Systematic name: S-adenosyl-L-methionine:NAD+ aminocarboxypropyltransferase
Comments: The enzyme, isolated from the bacterium Streptomyces sp. NCIMB40513, participates in the biosynthesis of the monoterpene alkaloids altemicidin, SB-203207 and SB-203208.The enzyme catalyse a pyridoxal phosphate-dependent [3+2]-annulation reaction between S-adenosyl-L-methionine (SAM) and NAD+. It transfers an aminocarboxypropyl group that combines with the pyridinium moiety of NAD+ to create a pentacyclic ring, forming a 6-azatetrahydroindane scaffold.
References:
1. Barra, L., Awakawa, T., Shirai, K., Hu, Z., Bashiri, G. and Abe, I. β-NAD as a building block in natural product biosynthesis. Nature 600 (2021) 754-758. [PMID: 34880494]
Accepted name: dehydropreakuammicine esterase
Reaction: 17-dehydropreakuammicine + H2O = norfluorocurarine + methanol + CO2
For diagram of reaction click here
Glossary: 17-dehydropreakuammicine = methyl (16S,19E)-17-oxocura-1,19-diene-16-carboxylate
norfluorocurarine = (19E)-cura-2(16),19-dien-17-al
Other name(s): norfluorocurarine synthase; NS1 (gene name); NS2 (gene name)
Systematic name: 17-dehydropreakuammicine hydrolase (decarboxylating)
Comments: The enzyme, characterized from the tree Strychnos nux-vomica, participates in the biosynthesis of strychnine. The enzyme catalyses the hydrolysis of a methyl ester, which is followed by the spontaneous decarboxylation of the resulting carboxyl group.
References:
1. Hong, B., Grzech, D., Caputi, L., Sonawane, P., Lopez, C.ER., Kamileen, M.O., Hernandez Lozada, N.J., Grabe, V. and O'Connor, S.E. Biosynthesis of strychnine. Nature 607 (2022) 617-622. [PMID: 35794473]
Accepted name: N-acetyllactosaminidase
Reaction: lacto-N-neotetraose + H2O = N-acetyllactosamine + lactose
Glossary: lacto-N-neotetraose = β-D-Gal-(1→4)-β-D-GlcNAc-(1→3)-β-D-Gal-(1→4)-D-Glc
N-acetyllactosamine = β-D-Gal-(1→4)-D-GlcNAc
Systematic name: oligosaccharide exo β-(1,3)-N-acetyllactosamine hydrolase (non-reducing end)
Comments: The enzyme, characterized from several bacterial species, hydrolyses the terminal N-acetyllactosamine residue (β-D-Gal-(1→4)-D-GlcNAc) from the non-reducing end of oligosaccharides with the structure β-D-Gal (1→4)-β-D-GlcNAc-(1→3)-β-D-Gal-(1→R). The enzyme also catalyses the activity of EC 3.2.1.140, lacto-N-biosidase, and is not active on oligosaccharides with a terminal GlcNAc residue.
References:
1. Vuillemin, M., Muschiol, J., Zhang, Y., Holck, J., Barrett, K., Morth, J.P., Meyer, A.S. and Zeuner, B. Discovery of lacto-N-biosidases and a novel N-acetyllactosaminidase activity in the CAZy family GH20: functional diversity and structural insights. Chembiochem (2024) e202400710. [PMID: 39239753]
Accepted name: cholesterol-5,6-oxide hydrolase
Reaction: (1) 5,6α-epoxy-5α-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
(2) 5,6β-epoxy-5β-cholestan-3β-ol + H2O = 5α-cholestane-3β,5α,6β-triol
For diagram of reactions, click here
Glossary: cholesterol = cholest-5-en-3β-ol
Other name(s): cholesterol-epoxide hydrolase; ChEH
Systematic name: 5,6α-epoxy-5α-cholestan-3β-ol hydrolase
Comments: The activity has been attributed to the microsomal antiestrogen binding site, a complex formed by EC 5.3.3.5, cholestenol Δ-isomerase, and EC 1.3.1.21, 7-dehydrocholesterol reductase [6]. Both 5,6α-epoxy-5α-cholestan-3β-ol and 5,6β-epoxy-5β-cholestan-3β-ol are substrates [3]. The product is a competitive inhibitor of the reaction. In vertebrates, five epoxide-hydrolase enzymes have been identified to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase) [3].
Links to other databases: BRENDA, EXPASY, G KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Levin, W., Michaud, D.P., Thomas, P.E. and Jerina, D.M. Distinct rat hepatic microsomal epoxide hydrolases catalyze the hydration of cholesterol 5,6 α-oxide and certain xenobiotic alkene and arene oxides. Arch. Biochem. Biophys. 220 (1983) 485-494. [PMID: 6401984]
2. Oesch, F., Timms, C.W., Walker, C.H., Guenthner, T.M., Sparrow, A., Watabe, T. and Wolf, C.R. Existence of multiple forms of microsomal epoxide hydrolases with radically different substrate specificities. Carcinogenesis 5 (1984) 7-9. [PMID: 6690087]
3. Sevanian, A. and McLeod, L.L. Catalytic properties and inhibition of hepatic cholesterol-epoxide hydrolase. J. Biol. Chem. 261 (1986) 54-59. [PMID: 3941086]
4. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41-59. [PMID: 11154734]
5. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1-51. [PMID: 15748653]
6. de Medina, P., Paillasse, M.R., Segala, G., Poirot, M. and Silvente-Poirot, S. Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands. Proc. Natl. Acad. Sci. USA 107 (2010) 13520-13525. [PMID: 20615952]
Accepted name: urease
Reaction: urea + 2 H2O = hydrogen carbonate + 2 NH3 (overall reaction)
(1a) urea + H2O = carbamate + NH3
(1b) carbamate + H2O = hydrogen carbonate + NH3 (spontaneous)
Systematic name: urea amidohydrolase
Comments: A nickel protein. Urease catalyses the hydrolysis of urea to yield ammonia and carbamate, which spontaneously hydrolyses to form carbonic acid and a second molecule of ammonia. In aqueous solutions the products convert to ammonium and hydrogen carbonate. The enzyme is widespread and is found in many bacteria, some archaea, and many eukaryotes, including plants, some invertebrates, and numerous eukaryotic microorganisms. Urease is one of the earlier enzymes to be studied, first obtained In 1874 [1,2], and named urease in 1890 [3]. The crystallization of urease in 1926 was a significant landmark in biochemistry, showing for the first time ever that enzymes are proteins and can be crystallized [4]. In 1975 it was found that the enzyme contains nickel ions in its active site [5,6].
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9002-13-5
References:
1. Musculus, F. Sur un Papier Reactif de l’Uree. Comptes Rendus 78 (1874) 132-134.
2. Musculus, F. Sur le Ferment de l’Uree. Comptes Rendus 82 (1876) 333-336.
3. Miquel, P. Sur un Ferment Soluble de l’Uree. Comptes Rendus 111 (1890) 397-399.
4. Sumner, J.B. The isolation and crystallization of the enzyme urease. Journal of Biological Chemistry 69(2) (1926) 435-441.
5. Dixon, N.E., Gazzola, T.C., Blakeley, R.L. and Zermer, B. Jack bean urease (EC 3.5.1.5). A metalloenzyme. A simple biological role for nickel? J. Am. Chem. Soc. 97 (1975) 4131-4133. [PMID: 1159216]
6. Dixon, N.E., Gazzola, C., Blakeley, R.L. and Zerner, B. Metal ions in enzymes using ammonia or amides. Science 191 (1976) 1144-1150. [PMID: 769157]
7. Sumner, J.B. Urease. In: Sumner, J.B. and Myrbäck, K. (Ed.), The Enzymes, vol. 1, Academic Press, New York, 1951, pp. 873-892.
8. Varner, J.E. Urease. In: Boyer, P.D., Lardy, H. and Myrbäck, K. (Ed.), The Enzymes, 2nd edn, vol. 4, Academic Press, New York, 1960, pp. 247-256.
Accepted name: 4-hydroxy-3-methoxy-5-polyprenylbenzoate decarboxylase
Reaction: 4-hydroxy-3-methoxy- 5-all-trans-polyprenylbenzoate = 2-methoxy-6-(all-trans-polyprenyl)phenol + CO2
Other name(s): COQ4
Systematic name: 4-hydroxy-3-methoxy-5-all-trans-polyprenylbenzoate carboxy-lyase
Comments: Requires Zn2+. The enzyme, found in eukaryotes, is involved in the biosynthesis of ubiquinone. The number of isoprenoid subunits in the side chain varies in different species. The enzyme does not have any specificity concerning the length of the polyprenyl tail, and accepts tails of various lengths with similar efficiency.
References:
1. Nicoll, C.R., Alvigini, L., Gottinger, A., Cecchini, D., Mannucci, B., Corana, F., Mascotti, M.L. and Mattevi, A. In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis. Nat. Catal. 7 (2024) 148-160. [PMID: 38425362]
Accepted name: UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactose:2-oxoglutarate ligase
Reaction: ATP + UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactose + 2-oxoglutarate = ADP + phosphate + UDP-yelosamine
Glossary: UDP-yelosamine = UDP-N-acetyl-D-fucosamine-4N-(2)-oxoglutarate = UDP-D-FucNAc-4N-(2)-oxoglutarate
Other name(s): Pyl
Systematic name: UDP-2-acetamido-4-amino-2,4,6-trideoxy-α-D-galactose:2-oxoglutarate ligase (ADP-forming)
Comments: The enzyme, discovered in the bacterium Bacillus cereus ATCC 14579, produces the unusual nucleotide sugar UDP-yelosamine, which is incorporated into the capsular polysaccharide of this organism.
References:
1. Hwang, S., Li, Z., Bar-Peled, Y., Aronov, A., Ericson, J. and Bar-Peled, M. The biosynthesis of UDP-D-FucNAc-4N-2-oxoglutarate (UDP-Yelosamine) in Bacillus cereus ATCC 14579: Pat and Pyl, an aminotransferase and an ATP-dependent Grasp protein that ligates 2-oxoglutarate to UDP-4-amino-sugars. J. Biol. Chem. 289 (2014) 35620-35632. [PMID: 25368324]