An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: 2-dehydro-3-deoxy-L-fuconate 4-dehydrogenase
Reaction: 2-dehydro-3-deoxy-L-fuconate + NAD+ = 2,4-didehydro-3-deoxy-L-fuconate + NADH + H+
For diagram of reaction click here
Glossary: 2-dehydro-3-deoxy-L-fuconate = (4S,5S)-4,5-dihydroxy-2-oxohexanoate
2,4-didehydro-3-deoxy-L-fuconate = (5S)-5-hydroxy-2,4-dioxohexanoate
Systematic name: 2-dehydro-3-deoxy-L-fuconate:NAD+ 4-oxidoreductase
Comments: The enzyme, originally described from the bacterium Xanthomonas campestris pv. campestris, participates in an L-fucose degradation pathway. It can also act on 2-dehydro-3-deoxy-L-galactonate and 2-dehydro-3-deoxy-D-pentonate.
References:
1. Yew, W.S., Fedorov, A.A., Fedorov, E.V., Rakus, J.F., Pierce, R.W., Almo, S.C. and Gerlt, J.A. Evolution of enzymatic activities in the enolase superfamily: L-fuconate dehydratase from Xanthomonas campestris. Biochemistry 45 (2006) 14582-14597. [PMID: 17144652]
2. Watanabe, S., Fukumori, F., Nishiwaki, H., Sakurai, Y., Tajima, K. and Watanabe, Y. Novel non-phosphorylative pathway of pentose metabolism from bacteria. Sci. Rep. 9 (2019) 155. [PMID: 30655589]
Accepted name: L-fucose dehydrogenase
For diagram of reaction click here
Reaction: β-L-fucopyranose + NADP+ = L-fucono-1,5-lactone + NADPH + H+
Systematic name: β-L-fucopyranose:NADP+ 1-oxidoreductase
Comments: The enzyme, characterized from the bacterium Burkholderia multivorans, participates in an L-fucose degradation pathway. The enzyme catalyses the oxidation of β-L-fucopyranose to L-fucono-1,5-lactone, which is unstable and is rapidly converted to L-fucono-1,4-lactone. The α anomer is not recognized. The enzyme can also act on β-L-galactopyranose and D-arabinose with lower activity. NADP is a better cosubstrate than NAD.
References:
1. Hobbs, M.E., Vetting, M., Williams, H.J., Narindoshvili, T., Kebodeaux, D.M., Hillerich, B., Seidel, R.D., Almo, S.C. and Raushel, F.M. Discovery of an L-fucono-1,5-lactonase from cog3618 of the amidohydrolase superfamily. Biochemistry 52 (2013) 239-253. [PMID: 23214453]
Accepted name: lactate dehydrogenase (NAD+,ferredoxin)
Reaction: lactate + 2 NAD+ + 2 reduced ferredoxin [iron-sulfur] cluster = pyruvate + 2 NADH + 2 oxidized ferredoxin [iron-sulfur] cluster
Other name(s): electron bifurcating LDH/Etf complex
Systematic name: lactate:NAD+,ferredoxin oxidoreductase
Comments: The enzyme, isolated from the bacterium Acetobacterium woodii, uses flavin-based electron confurcation to drive endergonic lactate oxidation with NAD+ as oxidant at the expense of simultaneous exergonic electron flow from reduced ferredoxin to NAD+.
References:
1. Weghoff, M.C., Bertsch, J. and Muller, V. A novel mode of lactate metabolism in strictly anaerobic bacteria. Environ. Microbiol. 17 (2015) 670-677. [PMID: 24762045]
Accepted name: 5-dehydrofumagillol 5-reductase
Reaction: fumagillol + NADP+ = 5-dehydrofumagillol + NADPH + H+
For diagram of reaction click here
Glossary: fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
Other name(s): af490 (gene name); Fma-KR
Systematic name: fumagillol:NADP+ 5-oxidoreductase
Comments: The enzyme, characterized from the mold Aspergillus fumigatus, participates in the biosynthesis of the meroterpenoid fumagillin. It is a partial polyketide synthase (PKS) consisting of only a dehydratase (DH) and a ketoreductase (KR) domain.
References:
1. Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426-4436. [PMID: 24568283]
[EC 1.3.1.110 Transferred entry: lactate dehydrogenase (NAD+, ferredoxin). Now EC 1.1.1.436, lactate dehydrogenase (NAD+,ferredoxin) (EC 1.3.1.110 created 2015, deleted 2022)]
Accepted name: acrylate reductase
Reaction: propanoate + NAD+ = acrylate + NADH + H+
Other name(s): ard (gene name); NADH:acrylate oxidoreductase
Systematic name: propanoate:NAD+ oxidoreductase
Comments: The enzyme, characterized from the marine bacterium Vibrio harveyi, enables the organism to utilize acrylate as the terminal electron acceptor for NADH regeneration under anaerobic conditions.
References:
1. Bertsova, Y.V., Serebryakova, M.V., Baykov, A.A. and Bogachev, A.V. A novel, NADH-dependent acrylate reductase in Vibrio harveyi. Appl. Environ. Microbiol. 88 (2022) e0051922. [PMID: 35612301]
Accepted name: fumarate reductase (cytochrome)
Reaction: succinate + 2 ferricytochrome c = fumarate + 2 ferrocytochrome c
Other name(s): fccA (gene name); fcc3 (gene name); flavocytochrome c3
Systematic name: succinate:ferricytochrome-c oxidoreductase
Comments: Contains a non-covalently bound FAD cofactor and four heme c groups. The enzyme, characterized from the bacterium Shewanella frigidimarina, is a soluble periplasmic protein that functions as a terminal electron acceptor during anaerobic growth. The direct electron donor is the membrane-bound tetraheme c-type cytochrome CymA (EC 7.1.1.8, quinol—cytochrome-c reductase), which receives the electrons from the membrane quinol pool.
References:
1. Pealing, S.L., Black, A.C., Manson, F.D., Ward, F.B., Chapman, S.K. and Reid, G.A. Sequence of the gene encoding flavocytochrome c from Shewanella putrefaciens: a tetraheme flavoenzyme that is a soluble fumarate reductase related to the membrane-bound enzymes from other bacteria. Biochemistry 31 (1992) 12132-12140. [PMID: 1333793]
2. Pealing, S.L., Cheesman, M.R., Reid, G.A., Thomson, A.J., Ward, F.B. and Chapman, S.K. Spectroscopic and kinetic studies of the tetraheme flavocytochrome c from Shewanella putrefaciens NCIMB400. Biochemistry 34 (1995) 6153-6158. [PMID: 7742319]
3. Gordon, E.HJ., Pealing, S.L., Chapman, S.K., Ward, F.B. and Reid, G.A. Physiological function and regulation of flavocytochrome c3, the soluble fumarate reductase from Shewanella putrefaciens NCIMB 400. Microbiology (Reading) 144 (1998) 937-945. [PMID: 9579067]
4. Doherty, M.K., Pealing, S.L., Miles, C.S., Moysey, R., Taylor, P., Walkinshaw, M.D., Reid, G.A. and Chapman, S.K. Identification of the active site acid/base catalyst in a bacterial fumarate reductase: a kinetic and crystallographic study. Biochemistry 39 (2000) 10695-10701. [PMID: 10978153]
5. Reid, G.A., Miles, C.S., Moysey, R.K., Pankhurst, K.L. and Chapman, S.K. Catalysis in fumarate reductase. Biochim. Biophys Acta 1459 (2000) 310-315. [PMID: 11004445]
6. Schwalb, C., Chapman, S.K. and Reid, G.A. The membrane-bound tetrahaem c-type cytochrome CymA interacts directly with the soluble fumarate reductase in Shewanella. Biochem Soc Trans. 30 (2002) 658-662. [PMID: 12196158]
Accepted name: nicotine dehydrogenase
Reaction: (S)-nicotine + 2 ferricytochrome c = N-methylmyosmine + 2 ferrocytochrome c + 2 H+
Glossary: (S)-nicotine = 3-[(S)-1-methylpyrrolidin-2-yl]pyridine
N-methylmyosamine = 3-(1-methyl-4,5-dihydro-1H-pyrrol-2-yl)pyridine
Other name(s): nicA2 (gene name)
Systematic name: (S)-nicotine:cytochrome c oxidoreductase (N-methylmimosine-forming)
Comments: The enzyme, characterized from the bacterium Pseudomonas putida S16, contains an FAD cofactor and belongs to the flavin-containing amine oxidase family. The enzyme from this bacterium is specific for the c-type cytochrome CycN. The product undergoes spontaneous hydrolysis to form pseudooxynicotine.
References:
1. Tang, H., Wang, L., Wang, W., Yu, H., Zhang, K., Yao, Y. and Xu, P. Systematic unraveling of the unsolved pathway of nicotine degradation in Pseudomonas. PLoS Genet. 9 (2013) e1003923. [PMID: 24204321]
2. Dulchavsky, M., Clark, C.T., Bardwell, J.CA. and Stull, F. A cytochrome c is the natural electron acceptor for nicotine oxidoreductase. Nat. Chem. Biol. 17 (2021) 344-350. [PMID: 33432238]
Accepted name: pseudooxynicotine dehydrogenase
Reaction: pseudooxynicotine + H2O + 2 ferricytochrome c = 4-oxo-4-(pyridin-3-yl)butanal + methylamine + 2 ferrocytochrome c + 2 H+
Glossary: pseudooxynicotine = 4-(methylamino)-1-(pyridin-3-yl)butan-1-one
Other name(s): pnaO (gene name)
Systematic name: 4-(methylamino)-1-(pyridin-3-yl)butan-1-one:c-type cytochrome oxidoreductase (methylamine releasing)
Comments: Contains one non-covalently bound FAD molecule per dimer. This enzyme, characterized from the soil bacteria Pseudomonas sp. HZN6 and Pseudomonas putida S16, is involved the nicotine degradation.
References:
1. Qiu, J., Ma, Y., Wen, Y., Chen, L., Wu, L. and Liu, W. Functional identification of two novel genes from Pseudomonas sp. strain HZN6 involved in the catabolism of nicotine. Appl. Environ. Microbiol. 78 (2012) 2154-2160. [PMID: 22267672]
2. Choudhary, V., Wu, K., Zhang, Z., Dulchavsky, M., Barkman, T., Bardwell, J.CA. and Stull, F. The enzyme pseudooxynicotine amine oxidase from Pseudomonas putida S16 is not an oxidase, but a dehydrogenase. J. Biol. Chem. (2022) 102251. [PMID: 35835223]
[EC 1.4.3.24 Transferred entry: pseudooxynicotine oxidase, now classified as EC 1.4.2.3, pseudooxynicotine dehydrogenase (EC 1.4.3.24 created 2012, deleted 2022)]
Accepted name: homospermidine oxidase
Reaction: sym-homospermidine + 2 O2 + H2O = 1-formylpyrrolizidine + 2 H2O2 + 2 NH3 (overall reaction)
(1a) sym-homospermidine + O2 = N-(4-aminobutylpyrrolinium) ion + H2O2 + NH3
(1b) N-(4-aminobutylpyrrolinium) ion + O2 + H2O = N-(4-oxobutylpyrrolinium) ion + NH3 + H2O2
(1c) N-(4-oxobutylpyrrolinium) ion = 1-formylpyrrolizidine (spontaneous)
Glossary: (-)-trachelanthamidine = (1R,7aS)-hexahydro-1H-pyrrolizin-1-ylmethanol
Other name(s): HSO
Systematic name: homospermidine:oxygen oxidase (deaminating, cyclizing)
Comments: The copper-containing enzyme has been isolated from the plant Heliotropium indicum. It is involved in the biosynthesis of the pyrrolizidine alkaloid (-)-trachelanthamidine which acts as a secondary metabolite for the defense against herbivores. The oxidation of sym-homospermidine proceeds in three steps and results in a cyclization.
References:
1. Zakaria, M.M., Stegemann, T., Sievert, C., Kruse, L.H., Kaltenegger, E., Girreser, U., Cicek, S.S., Nimtz, M. and Ober, D. Insights into polyamine metabolism: homospermidine is double-oxidized in two discrete steps by a single copper-containing amine oxidase in pyrrolizidine alkaloid biosynthesis. Plant Cell 34 (2022) 2364-2382. [PMID: 35212762]
Accepted name: methylcytosine dioxygenase
Reaction: (1) 5-methylcytosine in DNA + 2-oxoglutarate + O2 = 5-hydroxymethylcytosine in DNA + succinate + CO2
(2) 5-hydroxymethylcytosine in DNA + 2-oxoglutarate + O2 = 5-formylcytosine in DNA + succinate + CO2 + H2O
(3) 5-formylcytosine in DNA + 2-oxoglutarate + O2 = 5-carboxycytosine in DNA + succinate + CO2
Other name(s): TET1 (gene name); TET2 (gene name); TET3 (gene name)
Systematic name: 5-methylcytosine in DNA,2-oxoglutarate:oxygen oxidoreductase
Comments: The TET proteins mediate iterative oxidation of 5-methylcytosine in DNA (5mc) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC and 5caC are recognized by EC 3.2.2.29, thymine-DNA glycosylase (TDG), which excises them, leaving an apyrimidinic site. Coupled with the base excision repair (BER) pathway, these activities result in a cytosine demethylation pathway.
References:
1. Ito, S., D'Alessio, A.C., Taranova, O.V., Hong, K., Sowers, L.C. and Zhang, Y. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature 466 (2010) 1129-1133. [PMID: 20639862]
2. Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C. and Zhang, Y. Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine. Science 333 (2011) 1300-1303. [PMID: 21778364]
3. He, Y.F., Li, B.Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., Sun, Y., Li, X., Dai, Q., Song, C.X., Zhang, K., He, C. and Xu, G.L. Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science 333 (2011) 1303-1307. [PMID: 21817016]
4. Maiti, A. and Drohat, A.C. Thymine DNA glycosylase can rapidly excise 5-formylcytosine and 5-carboxylcytosine: potential implications for active demethylation of CpG sites. J. Biol. Chem. 286 (2011) 35334-35338. [PMID: 21862836]
5. Zhang, L., Lu, X., Lu, J., Liang, H., Dai, Q., Xu, G.L., Luo, C., Jiang, H. and He, C. Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA. Nat. Chem. Biol. 8 (2012) 328-330. [PMID: 22327402]
Accepted name: (–)-cyclopenine synthase
Reaction: (1) cyclopeptine + 2-oxoglutarate + O2 = dehydrocyclopeptine + succinate + CO2 + H2O
(2) dehydrocyclopeptine + 2-oxoglutarate + O2 = (–)-cyclopenine + succinate + CO2
Glossary: cyclopeptine = (3S)-3-benzyl-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione
(–)-cyclopenine = (3S,3'R)-4-methyl-3'-phenyl-1H-spiro[1,4-benzodiazepine-3,2'-oxirane]-2,5-dione
Other name(s): asqJ (gene name)
Systematic name: cyclopeptine,2-oxoglutarate:oxygen oxidoreductase ((–)-cyclopenine-forming)
Comments: This fungal enzyme is involved in the biosynthesis of quinolone compounds. it catalyses two oxidation reactions: the first reaction results in a desaturation; the second reaction is a monooxygenation of the double bond, forming an epoxide. The enzyme is also active with 4'-methoxycyclopeptine.
References:
1. Nover, L. and Luckner, M. Mixed functional oxygenations during the biosynthesis of cyclopenin and cyclopenol, benzodiazepine alkaloids of Penicillium cyclopium westling. Incorporation of molecular oxygen and NIH-shift. FEBS Lett. 3 (1969) 292-296. [PMID: 11947032]
2. Ishikawa, N., Tanaka, H., Koyama, F., Noguchi, H., Wang, C.C., Hotta, K. and Watanabe, K. Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids. Angew. Chem. Int. Ed. Engl. 53 (2014) 12880-12884. [PMID: 25251934]
3. Brauer, A., Beck, P., Hintermann, L. and Groll, M. Structure of the dioxygenase AsqJ: Mechanistic insights into a one-pot multistep quinolone antibiotic biosynthesis. Angew. Chem. Int. Ed. Engl. 55 (2016) 422-426. [PMID: 26553478]
4. Chang, W.C., Li, J., Lee, J.L., Cronican, A.A. and Guo, Y. Mechanistic investigation of a non-heme iron enzyme catalyzed epoxidation in (–)-4'-methoxycyclopenin biosynthesis. J. Am. Chem. Soc. 138 (2016) 10390-10393. [PMID: 27442345]
5. Song, X., Lu, J. and Lai, W. Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations. Phys Chem Chem Phys 19 (2017) 20188-20197. [PMID: 28726913]
6. Liao, H.J., Li, J., Huang, J.L., Davidson, M., Kurnikov, I., Lin, T.S., Lee, J.L., Kurnikova, M., Guo, Y., Chan, N.L. and Chang, W.C. Insights into the desaturation of cyclopeptin and its C3 epimer catalyzed by a non-heme Iron enzyme: structural characterization and mechanism elucidation. Angew. Chem. Int. Ed. Engl. 57 (2018) 1831-1835. [PMID: 29314482]
7. Mader, S.L., Brauer, A., Groll, M. and Kaila, V.RI. Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ. Nat. Commun. 9 (2018) 1168. [PMID: 29563492]
8. Wojdyla, Z. and Borowski, T. On how the binding cavity of AsqJ dioxygenase controls the desaturation reaction regioselectivity: a QM/MM study. J. Biol. Inorg. Chem. 23 (2018) 795-808. [PMID: 29876666]
9. Li, J., Liao, H.J., Tang, Y., Huang, J.L., Cha, L., Lin, T.S., Lee, J.L., Kurnikov, I.V., Kurnikova, M.G., Chang, W.C., Chan, N.L. and Guo, Y. Epoxidation catalyzed by the nonheme iron(II)- and 2-oxoglutarate-dependent oxygenase, AsqJ: mechanistic elucidation of oxygen atom transfer by a ferryl intermediate. J. Am. Chem. Soc. 142 (2020) 6268-6284. [PMID: 32131594]
10. Tang, H., Tang, Y., Kurnikov, I.V., Liao, H.J., Chan, N.L., Kurnikova, M.G., Guo, Y. and Chang, W.C. Harnessing the substrate promiscuity of dioxygenase AsqJ and developing efficient chemoenzymatic synthesis for quinolones. ACS Catal. 11 (2021) 7186-7192. [PMID: 35721870]
Accepted name: 5-dehydro-6-demethoxyfumagillol dioxygenase
Reaction: 5-dehydro-6-demethoxyfumagillol + 2-oxoglutarate + O2 = 5-dehydro-6-demethoxy-6-hydroxyfumagillol + succinate + CO2
For diagram of reaction click here
Glossary: fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
Other name(s): fmaF (gene name); Fma-C6H
Systematic name: 5-dehydro-6-demethoxyfumagillol,2-oxoglutarate:oxygen oxidoreductase (6-hydroxylating)
Comments: Requires iron(II). The enzyme, characterized from the mold Aspergillus fumigatus, participates in the biosynthesis of the meroterpenoid fumagillin.
References:
1. Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426-4436. [PMID: 24568283]
Accepted name: rifampicin monooxygenase
Reaction: rifampicin + NAD(P)H + O2 = 2-hydroxyrifampicin + NAD(P)+ + H2O
For diagram of reaction click here
Glossary: rifampicin = (2S,12Z,14E,16S,17S,18R,19R,20R,21S,22R,23S,24E)-5,6,9,17,19-pentahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-{[(E)-(4-methylpiperazin-1-yl)imino]methyl}-1,11-dioxo-1,2-dihydro-2,7-(epoxypentadeca-1,11,13-trienoimino)nathpho[2,1-b]furan-21-yl acetate
Other name(s): RIF-O; ROX; RIFMO; rifampicin:NAD(P)H:oxygen oxidoreductase (2'-N-hydroxyrifampicin-forming) (incorrect)
Systematic name: rifampicin:NAD(P)H:oxygen oxidoreductase (C2-hydroxyrifampicin-forming; ring-cleaving)
Comments: The enzyme has been found in a variety of environmental bacteria, notably Rhodococcus, Nocardia, and Streptomyces. It hydroxylates C-2 of rifampicin leading to its macro-ring cleaving.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Andersen, S.J., Quan, S., Gowan, B. and Dabbs, E.R. Monooxygenase-like sequence of a Rhodococcus equi gene conferring increased resistance to rifampin by inactivating this antibiotic. Antimicrob. Agents Chemother. 41 (1997) 218-221. [PMID: 8980786]
2. Hoshino, Y., Fujii, S., Shinonaga, H., Arai, K., Saito, F., Fukai, T., Satoh, H., Miyazaki, Y. and Ishikawa, J. Monooxygenation of rifampicin catalyzed by the rox gene product of Nocardia farcinica: structure elucidation, gene identification and role in drug resistance. J. Antibiot. (Tokyo) 63 (2010) 23-28. [PMID: 19942945]
3. Koteva, K., Cox, G., Kelso, J.K., Surette, M.D., Zubyk, H.L., Ejim, L., Stogios, P., Savchenko, A., Sørensen, D. and Wright, G.D. Rox, a rifamycin resistance enzyme with an unprecedented mechanism of action. Cell Chem Biol 25 (2018) 403-412.e5. [PMID: 29398560]
4. Liu, L.K., Dai, Y., Abdelwahab, H., Sobrado, P. and Tanner, J.J. Structural evidence for rifampicin monooxygenase inactivating rifampicin by cleaving Its ansa-bridge. Biochemistry 57 (2018) 2065-2068. [PMID: 29578336]
Accepted name: 2,4,6-trichlorophenol monooxygenase
Reaction: 2,4,6-trichlorophenol + FADH2 + O2 = 6-chloro-2-hydroxy-1,4-benzoquinone + 2 Cl- + FAD (overall reaction)
(1a) 2,4,6-trichlorophenol + FADH2 + O2 = 2,6-dichloro-1,4-benzoquinone + Cl- + FAD + H2O
(1b) 2,6-dichloro-1,4-benzoquinone + H2O = 6-chloro-2-hydroxy-1,4-benzoquinone + Cl-
Other name(s): tcpA (gene name)
Systematic name: 2,4,6-trichlorophenol,FADH2:oxygen oxidoreductase (dechlorinating)
Comments: The enzyme, characterized from Cupriavidus pinatubonensis, participates in the degradation of 2,4,6-trichlorophenol, a compound that has been used for decades as a wood preservative. The enzyme is a multifunctional flavin-dependent monooxygenase that catalyses two different reactions to displace two chlorine atoms, a monooxygenase reaction followed by a hydrolysis reaction that takes advantage of the reactivity of the product of the first reaction, 2,6-dichloro-1,4-benzoquinone [2]. The large amount of FADH2 that is required is generated by a dedicated flavin reductase (TcpB). cf. EC 1.14.14.172, 3,5,6-trichloropyridin-2-ol monooxygenase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Louie, T.M., Webster, C.M. and Xun, L. Genetic and biochemical characterization of a 2,4,6-trichlorophenol degradation pathway in Ralstonia eutropha JMP134. J. Bacteriol. 184 (2002) 3492-3500. [PMID: 12057943]
2. Xun, L. and Webster, C.M. A monooxygenase catalyzes sequential dechlorinations of 2,4,6-trichlorophenol by oxidative and hydrolytic reactions. J. Biol. Chem. 279 (2004) 6696-6700. [PMID: 14662756]
3. Hayes, R.P., Webb, B.N., Subramanian, A.K., Nissen, M., Popchock, A., Xun, L. and Kang, C. Structural and catalytic differences between two FADH2-dependent monooxygenases: 2,4,5-TCP 4-monooxygenase (TftD) from Burkholderia cepacia AC1100 and 2,4,6-TCP 4-monooxygenase (TcpA) from Cupriavidus necator JMP134. Int. J. Mol. Sci. 13 (2012) 9769-9784. [PMID: 22949829]
Accepted name: 5-dehydro-6-demethoxyfumagillol synthase
Reaction: (+)-exo-β-bergamotene + 2 [reduced NADPH—hemoprotein reductase] + 3 O2 = 5-dehydro-6-demethoxyfumagillol + 2 [oxidized NADPH—hemoprotein reductase] + 3 H2O (overall reaction)
(1a) (+)-exo-β-bergamotene + [reduced NADPH—hemoprotein reductase] + O2 = (5R)-hydroxy-(+)-exo-β-bergamotene + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) (5R)-hydroxy-(+)-exo-β-bergamotene + O2 = (3S)-3-[2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-4-methylidenecyclohexan-1-one + H2O
(1c) (3S)-3-[2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-4-methylidenecyclohexan-1-one + [reduced NADPH—hemoprotein reductase] + O2 = 5-dehydro-6-demethoxyfumagillol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
Glossary: (+)-exo-β-bergamotene = β-trans-bergamotene = (1S,5S,6R)-6-methyl-2-methylidene-6-(4-methylpent-3-enyl)bicyclo[3.1.1]heptane
fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
fumagillin = (2E,4E,6E,8E)-10-({(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]oct-6-yl}oxy)-10-oxodeca-2,4,6,8-tetraenoate
Other name(s): fumagillin multifunctional cytochrome P450 monooxygenase; Fma-P450; fmaG (gene name)
Systematic name: (+)-exo-β-bergamotene,[reduced NADPH—hemoprotein reductase] oxidoreductase (5-dehydro-6-demethoxyfumagillol-producing)
Comments: The enzyme, characterized from the mold Aspergillus fumigatus, catalyses a complex transformation comprising hydroxylation, bicyclic ring-opening, and two epoxidations, generating the sesquiterpenoid core skeleton of fumagillin.
References:
1. Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426-4436. [PMID: 24568283]
Accepted name: tetraether lipid synthase
Reaction: (1) 2 a 2,3-bis-O-phytanyl-sn-glycero-phospholipid + 4 S-adenosyl-L-methionine + 2 reduced acceptor = a glycerol dibiphytanyl glycerol tetraether phospholipid + 4 L-methionine + 4 5'-deoxyadenosine + 2 acceptor
(2) a 3-bis-O-phytanyl-sn-glycero-phospholipid + 2 S-adenosyl-L-methionine + reduced acceptor = a macrocyclic archaeol phospholipid + 2 L-methionine + 2 5'-deoxyadenosine + acceptor
Glossary: 2,3-bis-O-phytanyl-sn-glycerol = archaeol
Other name(s): GDGT/MA synthase; GDGT/MAS; tetraether synthase; Tes; Mj0619 (locus name)
Systematic name: a 2,3-bis-O-phytanyl-sn-glycero-phospholipid:S-adenosyl-L-methionine,acceptor oxidoreductase (cyclyzing)
Comments: This archaeal enzyme catalyses a C—C bond formation during the biosynthesis of tetraether lipids. The bond is formed between the termini of two lipid tails from two glycerophospholipids to generate the macrocycle glycerol dibiphytanyl glycerol tetraether (GDGT). The enzyme does not distinguish whether the two lipids are connected in antiparallel or parallel geometry, resulting in formation of two forms of the product, which are known as caldarchaeol and isocaldarchaeol, respectively. The enzyme can also form macrocyclic archaeol phospholipids by joining the two lipid tails of a single substrate molecule. Even though the reaction shown here describes phospholipid substrates, the enzyme can also act on glycolipids or lipids that contains mixed types of polar head groups. The enzyme is a radical SAM enzyme that contains 3 [4Fe-4S] clusters and one mononuclear rubredoxin-like iron ion, each found in a separate domain. The enzyme uses the 5'-deoxyadenosyl radical to initiate the reaction, which involves the formation of an intermediate bond between the substrate carbon and a sulfur of one of the [4Fe-4S] clusters. Two radicals are needed per C-C bond formed. The source of the required additional electrons is not known.
References:
1. Zeng, Z., Chen, H., Yang, H., Chen, Y., Yang, W., Feng, X., Pei, H. and Welander, P.V. Identification of a protein responsible for the synthesis of archaeal membrane-spanning GDGT lipids. Nat. Commun. 13 (2022) 1545. [PMID: 35318330]
2. Lloyd, C.T., Iwig, D.F., Wang, B., Cossu, M., Metcalf, W.W., Boal, A.K. and Booker, S.J. Discovery, structure, and mechanism of a tetraether lipid synthase. Nature (2022) . [PMID: 35882349]
Accepted name: small RNA 2'-O-methyltransferase
Reaction: S-adenosyl-L-methionine + an [sRNA]-3'-end ribonucleotide = S-adenosyl-L-homocysteine + an [sRNA]-3'-end 2'-O-methylated ribonucleotide
Glossary: sRNA = small RNA
Other name(s): HENMT1 (gene name); HEN1 (gene name)
Systematic name: S-adenosyl-L-methionine:[sRNA]-3'-end ribonucleotide 2'-O-methyltransferase
Comments: The enzyme adds a 2'-O-methyl group to the ribose of the last nucleotide in several types of small RNAs (sRNAs), protecting the 3'-end of sRNAs from uridylation activity and subsequent degradation.
References:
1. Park, W., Li, J., Song, R., Messing, J. and Chen, X. CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Curr. Biol. 12 (2002) 1484-1495. [PMID: 12225663]
2. Yu, B., Yang, Z., Li, J., Minakhina, S., Yang, M., Padgett, R.W., Steward, R. and Chen, X. Methylation as a crucial step in plant microRNA biogenesis. Science 307 (2005) 932-935. [PMID: 15705854]
3. Kirino, Y. and Mourelatos, Z. 2'-O-methyl modification in mouse piRNAs and its methylase. Nucleic Acids Symp Ser (Oxf) (2007) 417-418. [PMID: 18029764]
4. Huang, Y., Ji, L., Huang, Q., Vassylyev, D.G., Chen, X. and Ma, J.B. Structural insights into mechanisms of the small RNA methyltransferase HEN1. Nature 461 (2009) 823-827. [PMID: 19812675]
5. Peng, L., Zhang, F., Shang, R., Wang, X., Chen, J., Chou, J.J., Ma, J., Wu, L. and Huang, Y. Identification of substrates of the small RNA methyltransferase Hen1 in mouse spermatogonial stem cells and analysis of its methyl-transfer domain. J. Biol. Chem. 293 (2018) 9981-9994. [PMID: 29703750]
Accepted name: 5-dehydro-6-demethoxy-6-hydroxyfumagillol O-methyltransferase
Reaction: S-adenosyl-L-methionine + 5-dehydro-6-demethoxy-6-hydroxyfumagillol = S-adenosyl-L-homocysteine + 5-dehydrofumagillol
For diagram of reaction click here
Glossary: fumagillol = (3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]octan-6-ol
Other name(s): Fma-MT; fmaD (gene name); af390-400 (gene name)
Systematic name: S-adenosyl-L-methionine:5-dehydro-6-demethoxy-6-hydroxyfumagillol 6-O-methyltransferase
Comments: The enzyme, characterized from the mold Aspergillus fumigatus, participates in the biosynthesis of the meroterpenoid fumagillin.
References:
1. Lin, H.C., Tsunematsu, Y., Dhingra, S., Xu, W., Fukutomi, M., Chooi, Y.H., Cane, D.E., Calvo, A.M., Watanabe, K. and Tang, Y. Generation of complexity in fungal terpene biosynthesis: discovery of a multifunctional cytochrome P450 in the fumagillin pathway. J. Am. Chem. Soc. 136 (2014) 4426-4436. [PMID: 24568283]
Accepted name: tRNA carboxymetyluridine synthase
Reaction: acetyl-CoA + uridine34 in tRNA + S-adenosyl-L-methionine + H2O = CoA + 5-(carboxymethyl)uridine34 in tRNA + L-methionine + 5'-deoxyadenosine
Other name(s): elongator complex; ELP3
Systematic name: acetyl-CoA:tRNA uridine carboxymethyltransferase
Comments: The enzyme, found in eukaryotes, most archaea, and some bacteria, catalyses the first step in modification of the wobble uridine base of certain tRNAs. In eukaryotes the enzyme is a complex of six conserved subunits, with ELP3 being the catalytic subunit. In archaea and bacteria the enzyme consists of a single subunit, homologous to ELP3. The enzyme contains an [4Fe-4S] cluster and uses radical chemistry. A 5'-deoxyadenosyl radical generated in the radical AdoMet (SAM) domain attacks the acetyl-CoA donor, activating its methyl group, which forms a C-C bond with C5 of the uridine moiety.
References:
1. Paraskevopoulou, C., Fairhurst, S.A., Lowe, D.J., Brick, P. and Onesti, S. The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Mol. Microbiol. 59 (2006) 795-806. [PMID: 16420352]
2. Selvadurai, K., Wang, P., Seimetz, J. and Huang, R.H. Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism. Nat. Chem. Biol. 10 (2014) 810-812. [PMID: 25151136]
3. Lin, T.Y., Abbassi, N.EH., Zakrzewski, K., Chramiec-Glabik, A., Jemiola-Rzeminska, M., Rozycki, J. and Glatt, S. The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase. Nat. Commun. 10 (2019) 625. [PMID: 30733442]
Accepted name: 4,3-α-glucanotransferase
Reaction: formation of a mixed (1→4)/(1→3)-α-D-glucan from (1→4)-α-D-glucans
Other name(s): gtfB (gene name) (ambiguous)
Systematic name: (1→4)-α-D-glucan:(1→4)/(1→3)-α-D-glucan 3-α-D-glucosyltransferase
Comments: The enzyme, characterized from the bacterium Lactobacillus fermentum NCC 2970, possesses hydrolysis and transglycosylase activities on malto-oligosaccharides with a degree of polymerization of at least 6, as well as polymers such as amylose, potato starch, and amylopectin. The enzyme, which belongs to glycoside hydrolase 70 (GH70) family, attaches the glucosyl residues by α(1→3) linkages in both linear and branched orientations. While capable of forming large polymers, the enzyme produces mainly oligosaccharides in vitro.
References:
1. Gangoiti, J., van Leeuwen, S.S., Gerwig, G.J., Duboux, S., Vafiadi, C., Pijning, T. and Dijkhuizen, L. 4,3-α-Glucanotransferase, a novel reaction specificity in glycoside hydrolase family 70 and clan GH-H. Sci. Rep. 7 (2017) 39761. [PMID: 28059108]
2. Pijning, T., Gangoiti, J., Te Poele, E.M., Borner, T. and Dijkhuizen, L. Insights into broad-specificity starch modification from the crystal structure of Limosilactobacillus reuteri NCC 2613 4,6-α-glucanotransferase GtfB. J. Agric. Food Chem. 69 (2021) 13235-13245. [PMID: 34708648]
Accepted name: β-1,2-glucosyltransferase
Reaction: [(1→2)-β-D-glucosyl]n + a D-glucoside = [(1→2)-β-D-glucosyl]n-1 + a β-D-glucosyl-(1→2)-D-glucoside
Systematic name: 1,2-β-D-glucan:D-glucoside 2-β-D-glucosyltransferase (configuration-retaining)
Comments: The enzyme, characterized from the bacterium Ignavibacterium album, transfers a glucosyl residue from the non-reducing end of a 1,2-β-D-glucan to a glucose residue of an acceptor molecule, forming a β(1,2) linkage. The donor molecule can be as small as sophorose (which contains two glucosyl residues). The enzyme has a very broad specificity for the acceptor, and can act on various aryl- and alkyl-glucosides. In addition, the accepting glucose unit can be in either α or β configuration.
References:
1. Kobayashi, K., Shimizu, H., Tanaka, N., Kuramochi, K., Nakai, H., Nakajima, M. and Taguchi, H. Characterization and structural analyses of a novel glycosyltransferase acting on the β-1,2-glucosidic linkages. J. Biol. Chem. 298 (2022) 101606. [PMID: 35065074]
Accepted name: 3-O-β-D-glucopyranosyl-β-D-glucuronide phosphorylase
Reaction: a 3-O-β-D-glucosyl-β-D-glucuronoside + phosphate = a β-D-glucuronoside + α-D-glucopyranose 1-phosphate
Other name(s): PBOR_13355 (locus name)
Systematic name: 3-O-β-D-glucopyranosyl-β-D-glucuronide:phosphate α-D-glucosyltransferase
Comments: The enzyme, characterized from the bacterium Paenibacillus borealis, catalyses a reversible reaction, transferring a glucosyl residue attached by a β(1,3) linkage to a D-glucuronate residue (either free or as a part of a β-D-glucuronide) to a free phosphate, generating α-D-glucopyranose 1-phosphate
References:
1. Isono, N., Mizutani, E., Hayashida, H., Katsuzaki, H. and Saburi, W. Functional characterization of a novel GH94 glycoside phosphorylase, 3-O-β-D-glucopyranosyl β-D-glucuronide phosphorylase, and implication of the metabolic pathway of acidic carbohydrates in Paenibacillus borealis. Biochem. Biophys. Res. Commun. 625 (2022) 60-65. [PMID: 35947916]
[EC 2.5.1.4 Transferred entry: adenosylmethionine cyclotransferase. Now classified as EC 4.4.1.42, S-adenosyl-L-methionine lyase (EC 2.5.1.4 created 1965, deleted 2022)]
[EC 2.6.1.8 Deleted entry: 2,5-diaminovalerate transaminase (EC 2.6.1.8 created 1961, modified 1982, deleted 2022)]
Accepted name: α-D-ribose-1-phosphate 5-kinase (ATP)
Reaction: ATP + α-D-ribose-1-phosphate = ADP + α-D-ribose 1,5-bisphosphate
Systematic name: ATP:α-D-ribose-1-phosphate 5-phosphotransferase
Comments: The enzyme, characterized from the halophilic archaeon Halopiger xanaduensis, participates in a non-carboxylating pentose bisphosphate pathway for nucleoside degradation, which is found in some halophilic archaea. cf. EC 2.7.1.212, α-D-ribose-1-phosphate 5-kinase (ADP).
References:
1. Sato, T., Utashima, S.H., Yoshii, Y., Hirata, K., Kanda, S., Onoda, Y., Jin, J.Q., Xiao, S., Minami, R., Fukushima, H., Noguchi, A., Manabe, Y., Fukase, K. and Atomi, H. A non-carboxylating pentose bisphosphate pathway in halophilic archaea. Commun Biol 5 (2022) 1290. [PMID: 36434094]
Accepted name: ceramide phosphoethanolamine synthase
Reaction: CDP-ethanolamine + a ceramide = a ceramide phosphorylethanolamine + CMP
Other name(s): Cpes (gene name)
Systematic name: CDP-ethanolamine:ceramide phosphoethanolaminyltransferase
Comments: The enzyme, studied from the fly Drosophila melanogaster, has homologues among the invertebrates, but not in other animal phyla. Its product, ceramide phosphoethanolamine, is synthesized as the main sphingolipid in cell membranes of arthropods, such as Drosophila and Musca, and is common in worms, bees, spiders, and scorpions. It has also been reported in deep-sea mussels and some sea snails, as well as protozoans and oomycetes. The enzyme requires a Mn(II) cofactor.
References:
1. Vacaru, A.M., Tafesse, F.G., Ternes, P., Kondylis, V., Hermansson, M., Brouwers, J.F., Somerharju, P., Rabouille, C. and Holthuis, J.C. Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. J. Cell Biol. 185 (2009) 1013-1027. [PMID: 19506037]
2. Vacaru, A.M., van den Dikkenberg, J., Ternes, P. and Holthuis, J.C. Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen. J. Biol. Chem. 288 (2013) 11520-11530. [PMID: 23449981]
Accepted name: L-fucono-1,5-lactonase
For diagram of reaction click here
Reaction: L-fucono-1,5-lactone + H2O = L-fuconate
Systematic name: L-fucono-1,5-lactone lactonohydrolase
Comments: The enzyme, characterized from the bacterium Burkholderia multivorans, participates in an L-fucose degradation pathway. The enzyme exhibits catalytic activity for the hydrolysis of several lactones, including L-fucono-1,4-lactone, D-arabinono-1,4-lactone, L-xylono-1,4-lactone, and L-galactono-1,4-lactone, but L-fucono-1,5-lactone is the best substrate.
References:
1. Hobbs, M.E., Vetting, M., Williams, H.J., Narindoshvili, T., Kebodeaux, D.M., Hillerich, B., Seidel, R.D., Almo, S.C. and Raushel, F.M. Discovery of an L-fucono-1,5-lactonase from cog3618 of the amidohydrolase superfamily. Biochemistry 52 (2013) 239-253. [PMID: 23214453]
Accepted name: ribulose-1,5-bisphosphate 5-phosphatase
Reaction: D-ribulose-1,5-bisphosphate + H2O = D-ribulose 1-phosphate + phosphate
Other name(s): RuBP 5-phosphatase
Systematic name: D-ribulose-1,5-bisphosphate 5-phosphohydrolase
Comments: The enzyme, characterized from the halophilic archaeon Halopiger xanaduensis, participates in a non-carboxylating pentose bisphosphate pathway for nucleoside degradation, which is found in some halophilic archaea. The enzyme requires both monovalent and divalent ions for optimal activity.
References:
1. Sato, T., Utashima, S.H., Yoshii, Y., Hirata, K., Kanda, S., Onoda, Y., Jin, J.Q., Xiao, S., Minami, R., Fukushima, H., Noguchi, A., Manabe, Y., Fukase, K. and Atomi, H. A non-carboxylating pentose bisphosphate pathway in halophilic archaea. Commun Biol 5 (2022) 1290. [PMID: 36434094]
Accepted name: α-3'-ketoglucosidase
Reaction: 3'-dehydrosucrose + H2O = 3-dehydro-D-glucopyranose + β-D-fructofuranose
Other name(s): 3'-keto-α-D-gluco-disaccharide hydrolase; α-3-ketoglucosidase (incorrect); 3-keto-glucoside hydrolase
Systematic name: 3'-dehydrosucrose 3'-dehydroglucohydrolase
Comments: The enzyme, originally characterized from the bacterium Agrobacterium tumefaciens, is specific for disaccharides that contain a 3-dehydro-α-D-glucose at the non-reducing end such as 3'-dehydrosucrose and 3'-dehydro-α,α-trehalose. It has no activity with disaccharides in which the glucose is in β conformation, and greatly reduced activity with disaccharides with an unmodified 3' position.
References:
1. Hayano, K. and Fukui, S. Alpha-3-ketoglucosidase of Agrobacterium tumefaciens. J. Bacteriol. 101 (1970) 692-697. [PMID: 5438043]
2. Liu, H., Shiver, A.L., Price, M.N., Carlson, H.K., Trotter, V.V., Chen, Y., Escalante, V., Ray, J., Hern, K.E., Petzold, C.J., Turnbaugh, P.J., Huang, K.C., Arkin, A.P. and Deutschbauer, A.M. Functional genetics of human gut commensal Bacteroides thetaiotaomicron reveals metabolic requirements for growth across environments. Cell Rep. 34 (2021) 108789. [PMID: 33657378]
Accepted name: palatinase
Reaction: palatinose + H2O = α-D-glucopyranose + D-fructofuranose
Glossary: palatinose = 6-O-α-D-glucopyranosyl-D-fructofuranose
Other name(s): palQ (gene name)
Systematic name: palatinose α-1,6-glucohydrolase
Comments: The enzyme, characterized from the bacterium Erwinia rhapontici, is specific for palatinose.
References:
1. Bornke, F., Hajirezaei, M. and Sonnewald, U. Cloning and characterization of the gene cluster for palatinose metabolism from the phytopathogenic bacterium Erwinia rhapontici. J. Bacteriol. 183 (2001) 2425-2430. [PMID: 11274100]
[EC 3.5.1.61 Transferred entry: mimosinase. Now EC 4.3.3.8, mimosinase (EC 3.5.1.61 created 1989, deleted 2022)]
Accepted name: prenyl-diphosphate phosphatase
Reaction: (1) prenyl diphosphate + H2O = prenyl phosphate + phosphate
(2) 3-methylbut-3-en-1-yl diphosphate + H2O = 3-methylbut-3-en-1-yl phosphate + phosphate
Glossary: isopentenyl = 3-methylbut-3-en-1-yl
prenyl = 3-methylbut-2-en-1-yl = dimethylallyl
dimethylallyl diphosphate = DMAPP
isopentenyl diphosphate = IPP
Systematic name: prenyl diphosphate/3-methylbut-3-en-1-yl diphosphate phosphohydrolase
Comments: The enzyme, characterized from the methanogenic archaeon Methanosarcina mazei, belongs to the Nudix hydrolase family (a superfamily of hydrolytic enzymes capable of cleaving nucleoside diphosphates linked to a moiety). Its main purpose is to provide the substrate for EC 2.5.1.129, flavin prenyltransferase.
References:
1. Ishibashi, Y., Matsushima, N., Ito, T. and Hemmi, H. Isopentenyl diphosphate/dimethylallyl diphosphate-specific Nudix hydrolase from the methanogenic archaeon Methanosarcina mazei. Biosci. Biotechnol. Biochem. 86 (2022) 246-253. [PMID: 34864834]
[EC 3.13.2.2 Transferred entry: S-adenosyl-L-methionine hydrolase (L-homoserine-forming). Now classified as EC 4.4.1.42, S-adenosyl-L-methionine lyase (EC 3.13.2.2 created 1972 as EC 3.3.1.2, modified 1976, modified 2018, transferred 2022 to EC 3.13.2.2, transferred 2022 to EC 4.4.1.42, deleted 2022)]
Accepted name: anthranilate synthase
Reaction: chorismate + L-glutamine = anthranilate + pyruvate + L-glutamate (overall reaction)
(1a) L-glutamine + H2O = L-glutamate + NH3
(1b) chorismate + NH3 = (2S)-2-amino-4-deoxychorismate + H2O
(1c) (2S)-2-amino-4-deoxychorismate = anthranilate + pyruvate
For diagram of reaction, click here
Other name(s): anthranilate synthetase; chorismate lyase; chorismate pyruvate-lyase (amino-accepting); TrpDE
Systematic name: chorismate pyruvate-lyase (amino-accepting; anthranilate-forming)
Comments: The enzyme, found in plants, fungi and bacteria is composed of two parts, a glutaminase subunit and a lyase subunit. The glutaminase produces ammonia that is channeled to the lyase subunit. In the absence of the glutaminase, the lyase can convert ammonia and chorismate into anthranilate. In some organisms, this enzyme is part of a multifunctional protein, together with one or more other components of the system for the biosynthesis of tryptophan [EC 2.4.2.18 (anthranilate phosphoribosyltransferase), EC 4.1.1.48 (indole-3-glycerol-phosphate synthase), EC 4.2.1.20 (tryptophan synthase) and EC 5.3.1.24 (phosphoribosylanthranilate isomerase)].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 9031-59-8
References:
1. Baker, T. and Crawford, I.P. Anthranilate synthetase. Partial purification and some kinetic studies on the enzyme from Escherichia coli. J. Biol. Chem. 241 (1966) 5577-5584. [PMID: 5333199]
2. Creighton, T.E. and Yanofsky, C. Chorismate to tryptophan (Escherichia coli) - anthranilate synthetase, PR transferase, PRA isomerase, InGP synthetase, tryptophan synthetase. Methods Enzymol. 17A (1970) 365-380.
3. Hütter, R., Niederberger, P. and DeMoss, J.A. Tryptophan synthetic genes in eukaryotic microorganisms. Annu. Rev. Microbiol. 40 (1986) 55-77. [PMID: 3535653]
4. Ito, J. and Yanofsky, C. Anthranilate synthetase, an enzyme specified by the tryptophan operon of Escherichia coli: Comparative studies on the complex and the subunits. J. Bacteriol. 97 (1969) 734-742. [PMID: 4886290]
5. Zalkin, H. and Kling, D. Anthranilate synthetase. Purification and properties of component I from Salmonella typhimurium. Biochemistry 7 (1968) 3566-3573. [PMID: 4878701]
6. Morollo, A.A. and Bauerle, R. Characterization of composite aminodeoxyisochorismate synthase and aminodeoxyisochorismate lyase activities of anthranilate synthase. Proc. Natl. Acad. Sci. USA 90 (1993) 9983-9987. [PMID: 8234345]
7. Kanno, T., Kasai, K., Ikejiri-Kanno, Y., Wakasa, K. and Tozawa, Y. In vitro reconstitution of rice anthranilate synthase: distinct functional properties of the α subunits OASA1 and OASA2. Plant Mol. Biol. 54 (2004) 11-22. [PMID: 15159631]
Accepted name: cyclopenase
Reaction: (–)-cyclopenine = viridicatin + methyl isocyanate
Glossary: (–)-cyclopenine = (3S,3'R)-4-methyl-3'-phenyl-1H-spiro[1,4-benzodiazepine-3,2'-oxirane]-2,5-dione
viridicatin = 3-hydroxy-4-phenyl-1H-quinolin-2-one
Other name(s): asqI (gene name)
Systematic name: (–)-cyclopenine methyl-isocyanate lyase (viridicatin-forming)
Comments: This fungal enzyme catalyses a key reaction in the biosynthesis of quinolone compounds, converting the benzodiazepine structure into a quinolone structure. The enzyme is also active with (–)-4'-methoxycyclopenine.
References:
1. Kishimoto, S., Hara, K., Hashimoto, H., Hirayama, Y., Champagne, P.A., Houk, K.N., Tang, Y. and Watanabe, K. Enzymatic one-step ring contraction for quinolone biosynthesis. Nat. Commun. 9 (2018) 2826. [PMID: 30026518]
Accepted name: α-L-rhamnosyl-(1→4)-β-D-glucuronate lyase
Reaction: an α-L-rhamnose-(1→4)-β-D-glucuronide = α-L-rhamnopyranose + a 4-deoxy-α-L-threo-hex-4-enopyranuronoside
Other name(s): L-rhamnose-α-1,4-D-glucuronate lyase; FoRham (gene name)
Systematic name: α-L-rhamnosyl-(1→4)-β-D-glucuronate lyase
Comments: The enzyme, characterized from the phytopathogenic fungus Fusarium oxysporum, removes the rhamnosyl residue from α-L-rhamnosyl-(1→4)-β-D-glucuronate or from oligosaccharides that contain this motif at the non-reducing end, leaving an unsaturated glucuronate residue. Among its natural substrates is the type II arabinogalactan component of gum arabic.
References:
1. Kondo, T., Kichijo, M., Maruta, A., Nakaya, M., Takenaka, S., Arakawa, T., Fushinobu, S. and Sakamoto, T. Structural and functional analysis of gum arabic L-rhamnose-α-1,4-D-glucuronate lyase establishes a novel polysaccharide lyase family. J. Biol. Chem. 297 (2021) 101001. [PMID: 34303708]
Accepted name: (–)-cyatha-3,12-diene synthase
Reaction: geranylgeranyl diphosphate = (–)-cyatha-3,12-diene + diphosphate
Diagram of reaction click here
Glossary: (–)-cyatha-3,12-diene = (3aS,5aS,10aS)-3a,5a,8-trimethyl-1-(propan-2-yl)-2,3,4,5,6,9,10,10a-octahydrocyclohepta[e]indene
Other name(s): eriG (gene name); CyaTC
Systematic name: geranylgeranyl diphosphate-lyase [(–)-cyatha-3,12-diene-forming]
Comments: The enzyme, characterized from the fungi Hericium erinaceus and Cyathus africanus, requires Mg2+ for activity.
References:
1. Yang, Y.L., Zhang, S., Ma, K., Xu, Y., Tao, Q., Chen, Y., Chen, J., Guo, S., Ren, J., Wang, W., Tao, Y., Yin, W.B. and Liu, H. Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi. Angew. Chem. Int. Ed. Engl. 56 (2017) 4749-4752. [PMID: 28371074]
Accepted name: neoverrucosan-5β-ol synthase
Reaction: geranylgeranyl diphosphate + H2O = neoverrucosan-5β-ol + diphosphate
Diagram of reaction click here
Glossary: neoverrucosan-5β-ol = (1aS,3R,3aS,5aR,8bR,8cS,12S,14S)-1a,3a,5a-trimethyl-8-(propan-2-yl)tetradecahydrocyclopenta[a]cyclopropa[h]naphthalen-3-ol
Other name(s): SapTC1
Systematic name: geranylgeranyl- diphosphate diphosphate-lyase (neoverrucosan-5β-ol-forming)
Comments: Requires Mg2+. Characterized from the marine bacterium Saprospira grandis.
References:
1. Yang, Y.L., Zhang, S., Ma, K., Xu, Y., Tao, Q., Chen, Y., Chen, J., Guo, S., Ren, J., Wang, W., Tao, Y., Yin, W.B. and Liu, H. Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi. Angew. Chem. Int. Ed. Engl. 56 (2017) 4749-4752. [PMID: 28371074]
Accepted name: verrucosan-2β-ol synthase
Reaction: geranylgeranyl diphosphate + H2O = verrucosan-2β-ol + diphosphate
Diagram of reaction click here
Glossary: verrucosan-2β-ol = (1S,3aR,5aS,6aR,7aR,8S,8aR,9bR)-1-(propan-2-yl)tetradecahydrocyclopenta[a]cyclopropa[g]naphthalene-8-ol
Other name(s): ChlTC2
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (verrucosan-2β-ol-forming)
Comments: Requires Mg2+. Characterized from the bacterium Chloroflexus aurantiacus.
References:
1. Yang, Y.L., Zhang, S., Ma, K., Xu, Y., Tao, Q., Chen, Y., Chen, J., Guo, S., Ren, J., Wang, W., Tao, Y., Yin, W.B. and Liu, H. Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi. Angew. Chem. Int. Ed. Engl. 56 (2017) 4749-4752. [PMID: 28371074]
Accepted name: (R)-axinyssene synthase
Reaction: geranylgeranyl diphosphate = (R)-axinyssene + diphosphate
Diagram of reaction click here
Glossary: (R)-axinyssene = (4R)-4-[(5E)-6,10-dimethylundeca-1,5,9-trien-2-yl]-1-methylcyclohexene
Other name(s): CysTC2
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase [(R)-axinyssene-forming]
Comments: Requires Mg2+. Characterized from the bacterium Archangium violaceum.
References:
1. Yang, Y.L., Zhang, S., Ma, K., Xu, Y., Tao, Q., Chen, Y., Chen, J., Guo, S., Ren, J., Wang, W., Tao, Y., Yin, W.B. and Liu, H. Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi. Angew. Chem. Int. Ed. Engl. 56 (2017) 4749-4752. [PMID: 28371074]
Accepted name: lydicene synthase
Reaction: geranylgeranyl diphosphate = lydicene + diphosphate
Diagram of reaction click here
Glossary: lydicene = (4aR,6aS)-2,2,4α,6α,9-pentamethyl-2,3,4,5,6,7,10,11-octahydro-1Hcyclohepta[a]naphthalene
Other name(s): StlTC
Systematic name: geranylgerany-diphosphate diphosphate-lyase (lydicene-forming)
Comments: Requires Mg2+. Characterized from the bacterium Streptomyces lydicus.
References:
1. Yang, Y.L., Zhang, S., Ma, K., Xu, Y., Tao, Q., Chen, Y., Chen, J., Guo, S., Ren, J., Wang, W., Tao, Y., Yin, W.B. and Liu, H. Discovery and characterization of a new family of diterpene cyclases in bacteria and fungi. Angew. Chem. Int. Ed. Engl. 56 (2017) 4749-4752. [PMID: 28371074]
Accepted name: (+)-exo-β-bergamotene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (+)-exo-β-bergamotene + diphosphate
Diagram of reaction click here and mechanism click here
Glossary: (+)-exo-β-bergamotene = β-trans-bergamotene = (1S,5S,6R)-6-methyl-2-methylidene-6-(4-methylpent-3-enyl)bicyclo[3.1.1]heptane
fumagillin = w(2E,4E,6E,8E)-10-({(3R,4S,5S,6R)-5-methoxy-4-[(2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl]-1-oxaspiro[2.5]oct-6-yl}oxy)-10-oxodeca-2,4,6,8-tetraenoate
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-exo-β-bergamotene-forming]
Comments: The enzyme, characterized from the mold Aspergillus fumigatus, participates in the biosynthesis of the meroterpenoid fumagillin.
References:
1. Lin, H.C., Chooi, Y.H., Dhingra, S., Xu, W., Calvo, A.M. and Tang, Y. The fumagillin biosynthetic gene cluster in Aspergillus fumigatus encodes a cryptic terpene cyclase involved in the formation of β-trans-bergamotene. J. Am. Chem. Soc. 135 (2013) 4616-4619. [PMID: 23488861]
Accepted name: mimosinase
Reaction: L-mimosine + H2O = 3-hydroxy-4H-pyrid-4-one + pyruvate + ammonia (overall reaction)
(1a) L-mimosine = 3-hydroxy-4H-pyrid-4-one + 2-aminoprop-2-enoate
(1b) 2-aminoprop-2-enoate = 2-iminopropanoate
(1c) 2-iminopropanoate + H2O = pyruvate + ammonia
Glossary: L-mimosine = (2S)-2-amino-3-[3-hydroxy-4-oxopyridin-1(4H)-yl]propanoate
Other name(s): mimosine amidohydrolase (incorrect)
Systematic name: (2S)-2-amino-3-[3-hydroxy-4-oxopyridin-1(4H)-yl]propanoate 3-hydroxy-4H-pyrid-4-one-lyase (2-aminoprop-2-enoate-forming)
Comments: A pyridoxal-phosphate protein. The enzyme degrades the toxic amino acid L-mimosine. It cleaves a carbon-nitrogen bond, releasing 3-hydroxy-4H-pyrid-4-one and an unstable enamine product that tautomerizes to an imine form, which undergoes a hydrolytic deamination to form pyruvate and ammonia. It is thought to have evolved from EC 4.4.1.13, cysteine-S-conjugate β-lyase. It has been described in both mimosine-producing plants and some bacteria.
References:
1. Tangendjaja, B., Lowry, J.B. and Wills, R.H. Isolation of a mimosine degrading enzyme from Leucaena leaf. J. Sci. Food Agric. 37 (1986) 523-526.
2. Negi, V.S., Bingham, J.P., Li, Q.X. and Borthakur, D. A carbon-nitrogen lyase from Leucaena leucocephala catalyzes the first step of mimosine degradation. Plant Physiol. 164 (2014) 922-934. [PMID: 24351687]
3. Oogai, S., Fukuta, M., Watanabe, K., Inafuku, M. and Oku, H. Molecular characterization of mimosinase and cystathionine β-lyase in the Mimosoideae subfamily member Mimosa pudica. J. Plant Res. 132 (2019) 667-680. [PMID: 31368041]
4. Oogai, S., Fukuta, M., Inafuku, M. and Oku, H. Isolation and characterization of mimosine degrading enzyme from Arthrobacter sp. Ryudai-S1. World J. Microbiol. Biotechnol. 38 (2022) 172. [PMID: 35908235]
Accepted name: S-adenosyl-L-methionine lyase
Reaction: S-adenosyl-L-methionine = L-homoserine lactone + S-methyl-5'-thioadenosine
Other name(s): T3p01 (gene name); SAM lyase; SAMase; adenosylmethionine cyclotransferase; S-adenosyl-L-methionine alkyltransferase (cyclizing)
Systematic name: S-adenosyl-L-methionine S-methyl-5'-thioadenosine-lyase (cyclizing; L-homoserine lactone-forming)
Comments: The enzyme was originally described from the yeast Saccharomyces cerevisiae (as EC 2.5.1.4), though it had not been well characterized. It was also incorrectly described from several bacteriophages as a hydrolase (EC 3.13.2.2). Later work has shown the bacteriophage enzyme to be a lyase. The enzyme binds its substrate at the border between two subunits of a trimeric complex in a position that prevents it from interacting with water. Instead, the substrate reacts with itself and splits in two. The product, L-homoserine lactone, spontaneously hydrolyses to L-homoserine.
References:
1. Mudd, S.H. The mechanism of the enzymatic cleavage of S-adenosylmethionine to α-amino-γ-butyrolactone. J. Biol. Chem. 234 (1959) 1784-1786. [PMID: 13672964]
2. Mudd, S.H. Enzymatic cleavage of S-adenosylmethionine. J. Biol. Chem. 234 (1959) 87-92. [PMID: 13610898]
3. Hausmann, R. Synthesis of an S-adenosylmethionine-cleaving enzyme in T3-infected Escherichia coli and its disturbance by co-infection with enzymatically incompetent bacteriophage. J. Virol. 1 (1967) 57-63. [PMID: 4918233]
4. Studier, F.W. and Movva, N.R. SAMase gene of bacteriophage T3 is responsible for overcoming host restriction. J. Virol. 19 (1976) 136-145. [PMID: 781304]
5. Guo, X., Soderholm, A., Kanchugal, P., S., Isaksen, G.V., Warsi, O., Eckhard, U., Triguis, S., Gogoll, A., Jerlstrom-Hultqvist, J., Aqvist, J., Andersson, D.I. and Selmer, M. Structure and mechanism of a phage-encoded SAM lyase revises catalytic function of enzyme family. Elife 10 (2021) . [PMID: 33567250]
Accepted name: canavanine-γ-lyase
Reaction: L-canavanine + H2O = L-homoserine + N-hydroxyguanidine (overall reaction)
(1a) L-canavanine = vinylglycine + N-hydroxyguanidine
(1b) vinylglycine = (2E)-2-aminobut-2-enoate (spontaneous)
(1c) (2E)-2-aminobut-2-enoate + H2O = L-homoserine (spontaneous)
Other name(s): CangL
Systematic name: L-canavanine N-hydroxyguanidine-lyase (L-homoserine-forming)
Comments: A pyridoxal-phosphate protein. The enzyme, characterized from the bacterium Pseudomonas canavaninivorans, cleaves a carbon-oxygen bond, releasing N-hydroxyguanidine and an unstable enamine product that tautomerizes to an imine form, which is attacked by a water molecule to form L-homoserine.
References:
1. Hauth, F., Buck, H., Stanoppi, M., and Hartig, J. S. Canavanine utilization via homoserine and hydroxyguanidine by a PLP-dependent γ-lyase in Pseudomonadaceae and Rhizobiales. RSC Chemical Biology (0) .
Accepted name: thiohydroximate-O-sulfate sulfate/sulfur-lyase (nitrile-forming)
Reaction: an N-(sulfonatooxy)alkanimidothioate = a nitrile + sulfate + sulfur
Glossary: an N-(sulfonatooxy)alkanimidothioate = a thiohydroximate-O-sulfate
Other name(s): NSP (gene name); nitrile-specifier protein
Systematic name: thiohydroximate-O-sulfate sulfate/sulfur-lyase (nitrile-forming)
Comments: The enzyme is involved in the breakdown of glucosinolates. It can act on both aliphatic and aromatic glucosinolates, and forms nitrile-containing products. cf. EC 4.8.1.6, N-(sulfonatooxy)alkenimidothioic acid sulfate-lyase (epithionitrile-forming), and EC 4.8.1.7, phenyl-N-(sulfonatooxy)methanimidothioate sulfolyase.
References:
1. Kissen, R. and Bones, A.M. Nitrile-specifier proteins involved in glucosinolate hydrolysis in Arabidopsis thaliana. J. Biol. Chem. 284 (2009) 12057-12070. [PMID: 19224919]
2. Burow, M., Losansky, A., Muller, R., Plock, A., Kliebenstein, D.J. and Wittstock, U. The genetic basis of constitutive and herbivore-induced ESP-independent nitrile formation in Arabidopsis. Plant Physiol. 149 (2009) 561-574. [PMID: 18987211]
Accepted name: N-(sulfonatooxy)alkenimidothioic acid sulfate-lyase (epithionitrile-forming)
Reaction: N-(sulfonatooxy)alkenimidothioic acid with a terminal double bond = an epithionitrile + sulfate
Other name(s): ESP (gene name); epithionitrile-specifier protein; epithiospecifier protein
Systematic name: N-(sulfonatooxy)alkenimidothioic acid sulfate-lyase (epithionitrile-forming)
Comments: The enzyme is involved in the breakdown of glucosinolates. It acts only on aliphatic N-(sulfonatooxy)alkenimidothioic acids produced from ω-alkenyl-glucosinolates, and forms epithionitrile-containing products. cf. EC 4.8.1.5, thiohydroximate-O-sulfate sulfate/sulfur-lyase (nitrile-forming), and EC 4.8.1.7, phenyl-N-(sulfonatooxy)methanimidothioate sulfolyase.
References:
1. Lambrix, V., Reichelt, M., Mitchell-Olds, T., Kliebenstein, D.J. and Gershenzon, J. The Arabidopsis epithiospecifier protein promotes the hydrolysis of glucosinolates to nitriles and influences Trichoplusia ni herbivory. Plant Cell 13 (2001) 2793-2807. [PMID: 11752388]
2. Zabala M. de, T., Grant, M., Bones, A.M., Bennett, R., Lim, Y.S., Kissen, R. and Rossiter, J.T. Characterisation of recombinant epithiospecifier protein and its over-expression in Arabidopsis thaliana. Phytochemistry 66 (2005) 859-867. [PMID: 15845404]
Accepted name: phenyl-N-(sulfonatooxy)methanimidothioate sulfolyase
Accepted name: phenyl-N-(sulfonatooxy)methanimidothioate sulfolyase
Reaction: phenyl-N-(sulfonatooxy)methanimidothioate = benzylthiocyanate + sulfate
For diagram of reaction click here
Glossary: glucotropaeolin = 1-S-[(1Z)-2-phenyl-N-(sulfonatooxy)ethanimidoyl]-1-thio-β-D-glucopyranose
Other name(s): TFP (gene name) (ambiguous); thiocyanate-forming protein (ambiguous)
Systematic name: phenyl-N-(sulfonatooxy)methanimidothioate sulfate-lyase (benzylthiocyanate-forming)
Comments: The enzyme, characterized from the plant Lepidium sativum, is involved in the breakdown of the glucosinolate glucotropaeolin. Depending on the substrate, it can also form simple nitrile- and epithionitrile-containing products. cf. EC 4.8.1.5, thiohydroximate-O-sulfate sulfate/sulfur-lyase (nitrile-forming), and EC 4.8.1.6, N-(sulfonatooxy)alkenimidothioic acid sulfate-lyase (epithionitrile-forming).
References:
1. Burow, M., Bergner, A., Gershenzon, J. and Wittstock, U. Glucosinolate hydrolysis in Lepidium sativum - identification of the thiocyanate-forming protein. Plant Mol. Biol. 63 (2007) 49-61. [PMID: 17139450]
Accepted name: N-(sulfonatooxy)prop-2-enimidothioate sulfolyase
Reaction: (1) N-(sulfonatooxy)prop-2-enimidothioate = prop-2-enylthiocyanate + sulfate
(2) N-(sulfonatooxy)prop-2-enimidothioate = 2-(thiiran-2-yl)acetonitrile + sulfate
Other name(s): TFP (gene name) (ambiguous); thiocyanate-forming protein (ambiguous)
Systematic name: N-(sulfonatooxy)prop-2-enimidothioate sulfate-lyase (prop2-enylthiocyanate-forming)
Comments: The enzyme, characterized from the plant Thlaspi arvense, is involved in the breakdown of the glucosinolate sinigrin. Depending on the substrate, it can also form simple nitrile-containing products. cf. EC 4.8.1.5, thiohydroximate-O-sulfate sulfate/sulfur-lyase (nitrile-forming) and EC 4.8.1.6, N-(sulfonatooxy)alkenimidothioic acid sulfate-lyase (epithionitrile-forming).
References:
1. Kuchernig, J.C., Backenkohler, A., Lubbecke, M., Burow, M. and Wittstock, U. A thiocyanate-forming protein generates multiple products upon allylglucosinolate breakdown in Thlaspi arvense. Phytochemistry 72 (2011) 1699-1709. [PMID: 21783213]
2. Gumz, F., Krausze, J., Eisenschmidt, D., Backenkohler, A., Barleben, L., Brandt, W. and Wittstock, U. The crystal structure of the thiocyanate-forming protein from Thlaspi arvense, a kelch protein involved in glucosinolate breakdown. Plant Mol. Biol. 89 (2015) 67-81. [PMID: 26260516]
3. Eisenschmidt-Bonn, D., Schneegans, N., Backenkohler, A., Wittstock, U. and Brandt, W. Structural diversification during glucosinolate breakdown: mechanisms of thiocyanate, epithionitrile and simple nitrile formation. Plant J. 99 (2019) 329-343. [PMID: 30900313]
Accepted name: neopinone isomerase
Reaction: neopinone = codeinone
For diagram of reaction click here
Glossary: neopinone = 3-methoxy-17-methyl-8,14-didehydro-4,5α-epoxymorphinan-6-one
codeinone = 3-methoxy-17-methyl-7,8-didehydro-4,5α-epoxymorphinan-6-one
Other name(s): NISO (gene name)
Systematic name: neopinone Δ8-Δ7-isomerase
Comments: The enzyme, characterized from the opium poppy (Papaver somniferum), participates in the biosynthesis of morphine. It also catalyses the isomerization of neomorphinone and morphinone.
References:
1. Dastmalchi, M., Chen, X., Hagel, J.M., Chang, L., Chen, R., Ramasamy, S., Yeaman, S. and Facchini, P.J. Neopinone isomerase is involved in codeine and morphine biosynthesis in opium poppy. Nat. Chem. Biol. 15 (2019) 384-390. [PMID: 30886433]
[EC 7.1.3.2 Transferred entry: Na+-exporting diphosphatase. Now EC 7.2.3.1, Na+-exporting diphosphatase (EC 7.1.3.2 created 2021, deleted 2022)]
EC 7.2 Catalysing the translocation of inorganic cations
EC 7.2.3 Linked to the hydrolysis of diphosphate
Accepted name: Na+-exporting diphosphatase
Reaction: diphosphate + H2O + Na+[side 1] = 2 phosphate + Na+[side 2]
Other name(s): Na+-translocating membrane pyrophosphatase; sodium-translocating pyrophosphatase
Systematic name: diphosphate phosphohydrolase (Na+-transporting)
Comments: Requires Na+ and K+. This enzyme, found in some bacteria and archaea, couples the energy from diphosphate hydrolysis to active sodium translocation across the membrane. The enzyme is electrogenic, as the Na+ transport results in generation of a positive potential in the inner side of the membrane.
References:
1. Belogurov, G.A., Malinen, A.M., Turkina, M.V., Jalonen, U., Rytkonen, K., Baykov, A.A. and Lahti, R. Membrane-bound pyrophosphatase of Thermotoga maritima requires sodium for activity. Biochemistry 44 (2005) 2088-2096. [PMID: 15697234]
2. Malinen, A.M., Belogurov, G.A., Baykov, A.A. and Lahti, R. Na+-pyrophosphatase: a novel primary sodium pump. Biochemistry 46 (2007) 8872-8878. [PMID: 17605473]
3. Luoto, H.H., Belogurov, G.A., Baykov, A.A., Lahti, R. and Malinen, A.M. Na+-translocating membrane pyrophosphatases are widespread in the microbial world and evolutionarily precede H+-translocating pyrophosphatases. J. Biol. Chem. 286 (2011) 21633-21642. [PMID: 21527638]