An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: ureidoglycolate dehydrogenase [NAD(P)+]
Reaction: (S)-ureidoglycolate + NAD(P)+ = N-carbamoyl-2-oxoglycine + NAD(P)H + H+
For diagram of reaction, click here
Other name(s): ureidoglycolate dehydrogenase (ambiguous)
Systematic name: (S)-ureidoglycolate:NAD(P)+ oxidoreductase
Comments: Involved in catabolism of purines. The enzyme from the bacterium Arthrobacter allantoicus can use both NAD+ and NADP+ with similar activity. cf. EC 1.1.1.350, ureidoglycolate dehydrogenase (NAD+).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 62213-62-1
References:
1. van der Drift, C., van Helvoort, P.E.M. and Vogels, G.D. S-Ureidoglycolate dehydrogenase: purification and properties. Arch. Biochem. Biophys. 145 (1971) 465-469. [PMID: 4399430]
Accepted name: alcohol-forming fatty acyl-CoA reductase (NADPH)
Reaction: a long-chain acyl-CoA + 2 NADPH + 2 H+ = a long-chain alcohol + 2 NADP+ + CoA
Glossary: a long-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 13 to 22 carbon atoms.
Other name(s): FAR (gene name); long-chain acyl-CoA:NADPH reductase
Systematic name: NADPH:long-chain acyl-CoA reductase
Comments: The enzyme has a wide distribution and is found in bacteria, plants, fungi, and animals. The alcohol is formed by a four-electron reduction of fatty acyl-CoA. Although the reaction proceeds through an aldehyde intermediate, a free aldehyde is not released. Enzymes from different sources vary in their chain-length preference. cf. EC 1.2.1.108, alcohol-forming fatty acyl-CoA reductase (NADH).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Metz, J.G., Pollard, M.R., Anderson, L., Hayes, T.R. and Lassner, M.W. Purification of a jojoba embryo fatty acyl-coenzyme A reductase and expression of its cDNA in high erucic acid rapeseed. Plant Physiol. 122 (2000) 635-644. [PMID: 10712526]
2. Cheng, J.B. and Russell, D.W. Mammalian wax biosynthesis. I. Identification of two fatty acyl-Coenzyme A reductases with different substrate specificities and tissue distributions. J. Biol. Chem. 279 (2004) 37789-37797. [PMID: 15220348]
3. Doan, T.T., Carlsson, A.S., Hamberg, M., Bulow, L., Stymne, S. and Olsson, P. Functional expression of five Arabidopsis fatty acyl-CoA reductase genes in Escherichia coli. J. Plant Physiol. 166 (2009) 787-796. [PMID: 19062129]
4. Moto, K., Yoshiga, T., Yamamoto, M., Takahashi, S., Okano, K., Ando, T., Nakata, T. and Matsumoto, S. Pheromone gland-specific fatty-acyl reductase of the silkmoth, Bombyx mori. Proc. Natl. Acad. Sci. USA 100 (2003) 9156-9161. [PMID: 12871998]
Accepted name: alcohol-forming fatty acyl-CoA reductase (NADH)
Reaction: a long-chain acyl-CoA + 2 NADH + 2 H+ = a long-chain alcohol + 2 NAD+ + CoA
Glossary: a long-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 13 to 22 carbon atoms.
Other name(s): FAR (gene name); long-chain acyl-CoA:NADH reductase
Systematic name: NADH:long-chain acyl-CoA reductase
Comments: The enzyme has been characterized from the photosynthetic flagellate Euglena gracilis. The alcohol is formed by a four-electron reduction of fatty acyl-CoA by NADH. Although the reaction proceeds through an aldehyde intermediate, a free aldehyde is not released. cf. EC 1.2.1.84, alcohol-forming fatty acyl-CoA reductase (NADPH).
References:
1. Kolattukudy, P.E. Reduction of fatty acids to alcohols by cell-free preparations of Euglena gracilis. Biochemistry 9 (1970) 1095-1102. [PMID: 4313936]
2. Teerawanichpan, P. and Qiu, X. Fatty acyl-CoA reductase and wax synthase from Euglena gracilis in the biosynthesis of medium-chain wax esters. Lipids 45 (2010) 263-273. [PMID: 20195781]
Accepted name: thioredoxin-disulfide reductase (NADPH)
Reaction: thioredoxin + NADP+ = thioredoxin disulfide + NADPH + H+
Glossary: The term ‘oxidized thioredoxin’ has been replaced by ‘thioredoxin disulfide’ as the former is ambiguous
Other name(s): NADP-thioredoxin reductase; NADPH-thioredoxin reductase; thioredoxin reductase (NADPH); NADPH2:oxidized thioredoxin oxidoreductase; thioredoxin-disulfide reductase (ambiguous)
Systematic name: thioredoxin:NADP+ oxidoreductase
Comments: A flavoprotein (FAD). The enzyme restores the activity of thioredoxin by reducing an internal disulfide bridge. cf. EC 1.8.98.8, thioredoxin-disulfide reductase (factor 420-dependent).
Links to other databases: BRENDA, EXPASY, GTD, KEGG, MetaCyc, PDB, CAS registry number: 9074-14-0
References:
1. Moore, E.C., Reichard, P. and Thelander, L. Enzymatic synthesis of deoxyribonucleotides. V. Purification and properties of thioredoxin reductase from Escherichia coli B. J. Biol. Chem. 239 (1964) 3445-3452. [PMID: 14245401]
2. Speranza, M.L., Ronchi, S. and Minchiotti, L. Purification and characterization of yeast thioredoxin reductase. Biochim. Biophys. Acta 327 (1973) 274-281. [PMID: 4149839]
3. Arner, E.S. and Holmgren, A. Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 267 (2000) 6102-6109. [PMID: 11012661]
Accepted name: sulfur-oxidizing heterodisulfide reductase-like enzyme system (type I)
Reaction: [TusA sulfur-carrier protein]-S-sulfanyl-L-cysteine + 2 [LbpA protein]-N6-lipoyl-L-lysine + 3 H2O = [TusA sulfur-carrier protein]-L-cysteine + 2 [LbpA protein]-N6-dihydrolipoyl-L-lysine + sulfite
Other name(s): sHdr system (type I)
Systematic name: [TusA sulfur-carrier protein]-S-sulfanyl-L-cysteine:[LbpA protein]-N6-lipoyl-L-lysine oxidoreductase
Comments: This enzyme complex, usually referred to as the sHdr system (type I), is a cytoplasmic sulfur oxidation system found in many bacterial and archaeal sulfur oxidizers. The system consists of a dimer of the iron-sulfur flavoprotein sHdrA and one subunit each of the proposed catalytic subunit sHdrB1, the disulfide reductase sHdrB2, and the ferredoxin-like electron carrier proteins sHdrC1 and sHdrC2. The system oxidizes a sulfane sulfur, provided by the TusA sulfur-carrier protein, to sulfite, using a dedicated lipoylated protein (LbpA) as the electron acceptor.
References:
1. Boughanemi, S., Lyonnet, J., Infossi, P., Bauzan, M., Kosta, A., Lignon, S., Giudici-Orticoni, M.T. and Guiral, M. Microbial oxidative sulfur metabolism: biochemical evidence of the membrane-bound heterodisulfide reductase-like complex of the bacterium Aquifex aeolicus. FEMS Microbiol. Lett. 363 (2016) . [PMID: 27284018]
2. Koch, T. and Dahl, C. A novel bacterial sulfur oxidation pathway provides a new link between the cycles of organic and inorganic sulfur compounds. ISME J. 12 (2018) 2479-2491. [PMID: 29930335]
3. Cao, X., Koch, T., Steffens, L., Finkensieper, J., Zigann, R., Cronan, J.E. and Dahl, C. Lipoate-binding proteins and specific lipoate-protein ligases in microbial sulfur oxidation reveal an atpyical role for an old cofactor. Elife 7 (2018) . [PMID: 30004385]
4. Ernst, C., Kayastha, K., Koch, T., Venceslau, S.S., Pereira, I.AC., Demmer, U., Ermler, U. and Dahl, C. Structural and spectroscopic characterization of a HdrA-like subunit from Hyphomicrobium denitrificans. FEBS J. 288 (2021) 1664-1678. [PMID: 32750208]
5. Appel, L., Willistein, M., Dahl, C., Ermler, U. and Boll, M. Functional diversity of prokaryotic HdrA(BC) modules: Role in flavin-based electron bifurcation processes and beyond. Biochim Biophys Acta Bioenerg 1862 (2021) 148379. [PMID: 33460586]
6. Tanabe, T.S., Bach, E., D'Ermo, G., Mohr, M.G., Hager, N., Pfeiffer, N., Guiral, M. and Dahl, C. A cascade of sulfur transferases delivers sulfur to the sulfur-oxidizing heterodisulfide reductase-like complex. Protein Sci. 33 (2024) e5014. [PMID: 38747384]
Accepted name: thioredoxin-disulfide reductase (factor 420-dependent)
Reaction: thioredoxin + an oxidized factor 420 = thioredoxin disulfide + a reduced factor 420
Other name(s): F420-dependent thioredoxin-disulfide reductase; deazaflavin-dependent flavin-containing thioredoxin reductase; (coenzyme F420)-dependent thioredoxin-disulfide reductase
Systematic name: thioredoxin:factor 420 oxidoreductase
Comments: A flavoprotein (FAD). The enzyme is found only in methanogenic archaea living in deep-sea volcanoes, and requires high partial pressure of hydrogen, which effects the reducing potential of the F420/F420H2 pair. cf. EC 1.8.1.9, thioredoxin-disulfide reductase (NADPH).
References:
1. Susanti, D., Loganathan, U. and Mukhopadhyay, B. A novel F420-dependent thioredoxin reductase gated by low potential FAD: a tool for redox regulation in an anaerobe. J. Biol. Chem. 291 (2016) 23084-23100. [PMID: 27590343]
[EC 1.9.98.1 Transferred entry: iron—cytochrome-c reductase. now EC 1.16.2.1, iron—cytochrome-c reductase (EC 1.9.98.1 created 1972 as EC 1.9.99.1, transferred 2014 to EC 1.9.98.1, deleted 2024)]
Accepted name: torosachrysone 7,10′-coupling peroxygenase
Reaction: 2 (R)-torosachrysone + H2O2 = phlegmacin + 2 H2O
Glossary: (R)-torosachrysone = (3R)-3,8,9-trihydroxy-6-methoxy-3-methyl-3,4-dihydroanthracen-1(2H)-one
phlegmacin = 1,2′,5′,6,9,10′-hexahydroxy-3,7′-dimethoxy-2′,6-dimethyl-2′,3′,6,7-tetrahydro-[2,9′-bianthracene]-4′(1'H),8(5H)-dione
Other name(s): UPO1
Systematic name: (R)-torosachrysone:hydrogen-peroxide oxidoreductase (phlegmacin-forming)
Comments: The enzyme, characterized from the mushroom Calonarius odorifer, catalyses the regioselective coupling of two molecules of the phenolic compound (R)-torosachrysone at the corresponding C7 and C10′ positions, forming the 7,10′-coupled dimeric product (phlegmacin). The enzyme produces both atropisomers of the product.
References:
1. Platz, L., Lohr, N.A., Girkens, M.P., Eisen, F., Braun, K., Fessner, N., Bar, C., Huttel, W., Hoffmeister, D. and Muller, M. Regioselective oxidative phenol coupling by a mushroom unspecific peroxygenase. Angew. Chem. Int. Ed. Engl. 63 (2024) e202407425. [PMID: 38963262]
Accepted name: L-tryptophan 5-peroxygenase
Reaction: L-tryptophan + H2O2 = 5-hydroxy-L-tryptophan + H2O
Other name(s): luz15 (gene name); bacterial tryptophan 5-hydroxylase
Systematic name: L-tryptophan:hydrogen-peroxide 5-oxidoreductase
Comments: The enzyme from the bacterium Actinomadura luzonensis is involved in the biosynthesis of the antitumour and antiviral depsipeptide luzopeptin A. Contains a heme b cofactor. The enzyme can use O2 (and ascorbate) instead of H2O2, but the reaction with H2O2 is at least two orders of magnitude faster. cf. EC 1.14.16.4, tryptophan 5-monooxygenase.
References:
1. Shi, X., Zhao, G., Li, H., Zhao, Z., Li, W., Wu, M. and Du, Y.L. Hydroxytryptophan biosynthesis by a family of heme-dependent enzymes in bacteria. Nat. Chem. Biol. 19 (2023) 1415-1422. [PMID: 37653171]
Accepted name: taxane oxetanase 1
Reaction: taxa-4(20),11-dien-5α-yl acetate + [reduced NADPH—hemoprotein reductase] + O2 = 5,20-epoxytaxa-11-en-4α-yl acetate + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here and mechanism click here
Other name(s): TOT1; Chr9_74725878
Systematic name: taxa-4(20),11-dien-5α-yl acetate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (oxetane ring forming)
Comments: A cytochrome-P-450 (heme thiolate) enzyme. Demonstrated in the plant Taxus mairei (Maire's yew). It is involved in the biosynthesis of taxol (paclitaxel). The reaction involves epoxidation of the 4(20)-double bond followed by rearangement giving the oxetane ring.
References:
1. Jiang, B., Gao, L., Wang, H., Sun, Y., Zhang, X., Ke, H., Liu, S., Ma, P., Liao, Q., Wang, Y., Wang, H., Liu, Y., Du, R., Rogge, T., Li, W., Shang, Y., Houk, K.N., Xiong, X., Xie, D., Huang, S., Lei, X. and Yan, J. Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III. Science 383 (2024) 622-629. [PMID: 38271490]
Accepted name: taxoid 1β-hydroxylase
Reaction: 10-deacetyl-1-deoxybaccatin III + [reduced NADPH—hemoprotein reductase] + O2 = 10-deacetylbaccatin III + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
Other name(s): taxane 1β-hydroxylase; CYP725 A23-1; T1βOH
Systematic name: 10-deacetyl-1-deoxybaccatin III,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (1β-hydroxylating)
Comments: A cytochrome-P-450 (heme thiolate) enzyme involved in paclitaxel (taxol) biosynthesis. Isolated from the plant Taxus baccata (English 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: taxol side chain-2′-hydroxylase
Reaction: 3′-N-debenzoyl-2′-deoxytaxol + [reduced NADPH-hemoprotein reductase] + O2 = 3′-N-debenzoyltaxol + [oxidized NADPH-hemoprotein reductase] + H2O
For diagram of reaction click here
Other name(s): CYP73A171; T2'OH; TB506
Systematic name: 3′-N-debenzoyl-2′-deoxytaxol,[reduced NADPH-hemoprotein reductase]:oxygen oxidoreductase (2′-hydroxylating)
Comments: A cytochrome-P-450 (heme thiolate) enzyme isolated from the plant Taxus × media. The penultimate step in paclitaxel (taxol) biosynthesis.
References:
1. Sanchez-Munoz, R., Perez-Mata, E., Almagro, L., Cusido, R.M., Bonfill, M., Palazon, J. and Moyano, E. A novel hydroxylation step in the taxane biosynthetic pathway: a new approach to paclitaxel production by synthetic biology. Front Bioeng Biotechnol 8 (2020) 410. [PMID: 32528936]
2. Long, R.M. and Croteau, R. Preliminary assessment of the C13-side chain 2′-hydroxylase involved in taxol biosynthesis. Biochem. Biophys. Res. Commun. 338 (2005) 410-417. [PMID: 16137660]
Accepted name: ecgonone synthase
Reaction: (S)-4(1-methylpyrrolidin-2-yl)-3-oxobutanoate + [reduced NADPH—hemoprotein reductase] + O2 = ecgonone + [oxidized NADPH—hemoprotein reductase] + 2 H2O
For diagram of reaction click here.
Glossary: ecgonone = (1R,2R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate
Other name(s): CYP81AN15; CYP82M3
Systematic name: (S)-4(1-methylpyrrolidin-2-yl)-3-oxobutanoate,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (excogone forming)
Comments: A cytochrome P450 (heme thiolate) enzyme that has been isolated from the plants Atropa belladonna, Erythroxylum novogranatense and Anisodus acutangulus. It participates in biosynthesis of assorted tropane alkaloids.
References:
1. Bedewitz, M.A., Jones, A.D., D'Auria, J.C. and Barry, C.S. Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization. Nat. Commun. 9 (2018) 5281. [PMID: 30538251]
2. Wang, Y.J., Huang, J.P., Tian, T., Yan, Y., Chen, Y., Yang, J., Chen, J., Gu, Y.C. and Huang, S.X. Discovery and engineering of the cocaine biosynthetic pathway. J. Am. Chem. Soc. 144 (2022) 22000-22007. [PMID: 36376019]
3. Wang, Y.J., Tain, T., Yu, J.Y., Li, J., Xu, B., Chen, J., D'Auria, J.C., Huang, J.P. and Huang, S.X. Genomic and structural basis for evolution of tropane alkaloid biosynthesis. Proc. Natl. Acad. Sci. USA 120 (2023) e2302448120. [PMID: 37068250]
Accepted name: littorine mutase
Reaction: littorine + [reduced NADPH—hemoprotein reductase] + O2 = hyoscyamine aldehyde + [oxidized NADPH—hemoprotein reductase] + 2 H2O (overall reaction)
(1a) littorine + [reduced NADPH—hemoprotein reductase] + O2 = 3-hydroxylittorine + [oxidized NADPH—hemoprotein reductase] + H2O
(1b) 3-hydroxylittorine = hyoscamine aldehyde + H2O (spontaneous)
For diagram of reaction click here and mechanism click here.
Other name(s): CYP80F1
Systematic name: littorine,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (hyoscyamine aldehyde forming)
Comments: Isolated from the plants Hyoscyamus niger (black henbane) and Anisodus acutangulus. Involved in the biosynthesis of the alkaloids hyoscyamine (atropine) and scopalamine. The reaction involves hydroxylation of littorine, giving a 1,2-diol that undergoes a spontaneous dehydration accompanied by pinacol rearrangement.
References:
1. Li, R., Reed, D.W., Liu, E., Nowak, J., Pelcher, L.E., Page, J.E. and Covello, P.S. Functional genomic analysis of alkaloid biosynthesis in Hyoscyamus niger reveals a cytochrome P450 involved in littorine rearrangement. Chem. Biol. 13 (2006) 513-520. [PMID: 16720272]
2. Sandala, G.M., Smith, D.M. and Radom, L. The carbon-skeleton rearrangement in tropane alkaloid biosynthesis. J. Am. Chem. Soc. 130 (2008) 10684-10690. [PMID: 18627156]
3. Nasomjai, P., Reed, D.W., Tozer, D.J., Peach, M.J., Slawin, A.M., Covello, P.S. and O'Hagan, D. Mechanistic insights into the cytochrome P450-mediated oxidation and rearrangement of littorine in tropane alkaloid biosynthesis. Chembiochem 10 (2009) 2382-2393. [PMID: 19693762]
4. Cui, L., Huang, F., Zhang, D., Lin, Y., Liao, P., Zong, J. and Kai, G. Transcriptome exploration for further understanding of the tropane alkaloids biosynthesis in Anisodus acutangulus. Mol. Genet. Genomics 290 (2015) 1367-1377. [PMID: 25876163]
Accepted name: ortho-methoxyphenolase
Reaction: (1) para-substituted 2-methoxyphenol + O2 = meta-substituted 3-methoxy-1,2-benzoquinone + H2O
(2) 2 para-substituted 2,6-dimethoxyphenol + O2 = 2 meta-substituted 3-methoxy-1,2-benzoquinone + 2 methanol
(3) 2 meta-substituted 3-methoxybenzene-1,2-diol + O2 = 2 meta-substituted 3-methoxy-1,2-benzoquinone + 2 H2O
Systematic name: an ortho-methoxylated phenol:oxygen oxidoreductase (ortho-quinone-forming)
Comments: A group of coupled binuclear copper enzymes found in filamentous fungi. Unlike EC 1.14.18.1, tyrosinase, these enzymes exhibit a distinct preference for ortho-methoxylated phenolic compounds such as guaiacyl- and syringyl-type phenolics derived from lignin depolymerization. When acting on syringyl-type substrates (having two ortho-methoxy groups), but not on guaiacyl-type substrates (a single ortho-methoxy group), the enzyme catalyses oxidative demethoxylation releasing methanol. The enzymes accommodate a wide range of methoxylated phenolic substrates, with variability in the para-position substituent relative to the phenolic hydroxyl.
References:
1. Frommhagen, M., Mutte, S.K., Westphal, A.H., Koetsier, M.J., Hinz, S.WA., Visser, J., Vincken, J.P., Weijers, D., van Berkel, W.JH., Gruppen, H. and Kabel, M.A. Boosting LPMO-driven lignocellulose degradation by polyphenol oxidase-activated lignin building blocks. Biotechnol Biofuels 10 (2017) 121. [PMID: 28491137]
2. de Oliveira Gorgulho Silva, C., Vuillemin, M., Kabel, M.A., van Berkel, W.JH., Meyer, A.S. and Agger, J.W. Polyphenol oxidase products are priming agents for LPMO peroxygenase activity. ChemSusChem 16 (2023) e202300559. [PMID: 37278305]
3. de, O., G. Silva, C., Sun, P., Barrett, K., Sanders, M.G., van Berkel, W.JH., Kabel, M.A., Meyer, A.S. and Agger, J.W. Polyphenol Oxidase Activity on Guaiacyl and Syringyl Lignin Units. Angew. Chem. Int. Ed. Engl. 63 (2024) e202409324. [PMID: 39285758]
EC 1.16.2 With a cytochrome as acceptor
Accepted name: iron—cytochrome-c reductase
Reaction: ferrocytochrome c + Fe3+ = ferricytochrome c + Fe2+
Other name(s): iron-cytochrome c reductase; mtrC (gene name); omcA (gene name); omcB (gene name)
Systematic name: ferrocytochrome-c:Fe3+ oxidoreductase
Comments: The MtrC and OmcA proteins of the bacterium Shewanella oneidensis MR-1 are decaheme c-type cytochromes that reduce iron oxides extracellularly, passing the electrons to MtrA, another decaheme c-type cytochrome located in the periplasm.
References:
1. Beliaev, A.S., Saffarini, D.A., McLaughlin, J.L. and Hunnicutt, D. MtrC, an outer membrane decahaem c cytochrome required for metal reduction in Shewanella putrefaciens MR-1. Mol. Microbiol. 39 (2001) 722-730. [PMID: 11169112]
2. Myers, C.R. and Myers, J.M. Cell surface exposure of the outer membrane cytochromes of Shewanella oneidensis MR-1. Lett. Appl. Microbiol. 37 (2003) 254-258. [PMID: 12904229]
3. Lower, B.H., Shi, L., Yongsunthon, R., Droubay, T.C., McCready, D.E. and Lower, S.K. Specific bonds between an iron oxide surface and outer membrane cytochromes MtrC and OmcA from Shewanella oneidensis MR-1. J. Bacteriol. 189 (2007) 4944-4952. [PMID: 17468239]
4. Hartshorne, R.S., Reardon, C.L., Ross, D., Nuester, J., Clarke, T.A., Gates, A.J., Mills, P.C., Fredrickson, J.K., Zachara, J.M., Shi, L., Beliaev, A.S., Marshall, M.J., Tien, M., Brantley, S., Butt, J.N. and Richardson, D.J. Characterization of an electron conduit between bacteria and the extracellular environment. Proc. Natl. Acad. Sci. USA 106 (2009) 22169-22174. [PMID: 20018742]
5. Mitchell, A.C., Peterson, L., Reardon, C.L., Reed, S.B., Culley, D.E., Romine, M.R. and Geesey, G.G. Role of outer membrane c-type cytochromes MtrC and OmcA in Shewanella oneidensis MR-1 cell production, accumulation, and detachment during respiration on hematite. Geobiology 10 (2012) 355-370. [PMID: 22360295]
6. Jing, X., Wu, Y., Shi, L., Peacock, C.L., Ashry, N.M., Gao, C., Huang, Q. and Cai, P. Outer membrane c-type cytochromes OmcA and MtrC play distinct roles in enhancing the attachment of Shewanella oneidensis MR-1 cells to goethite. Appl. Environ. Microbiol. 86 (2020) . [PMID: 32978123]
Accepted name: hydrogen-dependent carbon dioxide reductase
Reaction: formate + 2 H+ = CO2 + H2
Other name(s): HCDR
Systematic name: formate:proton oxidoreductase
Comments: The enzyme, originally characterized from the acetogenic bacterium Acetobacterium woodii, catalyses the reduction of CO2 to formate with electrons provided by the oxidation of molecular hydrogen. It consists of two catalytic subunits - a hydrogenase and a formate dehydrogenase, which are connected by two types of electron transfer subunits. The enzyme forms membrane-anchored nanowires in which the electron-transfer subunits oligomerize through their C-terminal helices to form the backbone of the filament. The rapid electron transfer via the filaments enhances the activity of the enzyme, resulting in a very high catalytic turnover rate. While the reaction is similar to that catalysed by the formate hydrogenlyase complex, which is formed by EC 1.17.98.4, formate dehydrogenase (hydrogenase), and EC 1.12.7.2, ferredoxin hydrogenase, this enzyme is not biased towards formate oxidation, and does not require ferredoxin in order to complete the reaction (although it is able to use reduced ferredoxin instead of dihydrogen for the reduction of CO2).
References:
1. Schuchmann, K. and Muller, V. Direct and reversible hydrogenation of CO2 to formate by a bacterial carbon dioxide reductase. Science 342 (2013) 1382-1385. [PMID: 24337298]
2. Schuchmann, K., Vonck, J. and Muller, V. A bacterial hydrogen-dependent CO2 reductase forms filamentous structures. FEBS J. 283 (2016) 1311-1322. [PMID: 26833643]
3. Schwarz, F.M., Schuchmann, K. and Muller, V. Hydrogenation of CO2 at ambient pressure catalyzed by a highly active thermostable biocatalyst. Biotechnol. Biofuels 11 (2018) 237. [PMID: 30186365]
4. Dietrich, H.M., Righetto, R.D., Kumar, A., Wietrzynski, W., Trischler, R., Schuller, S.K., Wagner, J., Schwarz, F.M., Engel, B.D., Muller, V. and Schuller, J.M. Membrane-anchored HDCR nanowires drive hydrogen-powered CO2 fixation. Nature 607 (2022) 823-830. [PMID: 35859174]
Accepted name: 6-carboxymethyl-5-methyl-4-hydroxypyridin-2-ol 3-C-methyltransferase
Reaction: S-adenosyl-L-methionine + 6-carboxymethyl-5-methyl-4-hydroxypyridin-2-ol = S-adenosyl-L-homocysteine + 6-carboxymethyl-3,5-dimethyl-4-hydroxypyridin-2-ol
Glossary: guanylylpyridinol = [4-(5′-guanylyloxy)-6-hydroxy-3,5-dimethylpyridin-2-yl]acetate
Other name(s): hcgC (gene name)
Systematic name: S-adenosyl-L-methionine:6-carboxymethyl-5-methyl-4-hydroxypyridin-2-ol 3-C-methyltransferase
Comments: The enzyme, characterized from the archaeon Methanococcus maripaludis, participates in the biosynthesis of the iron-guanylylpyridinol (FeGP) cofactor of EC 1.12.98.2, 5,10-methenyltetrahydromethanopterin hydrogenase (also known as [Fe]-hydrogenase).
References:
1. Fujishiro, T., Bai, L., Xu, T., Xie, X., Schick, M., Kahnt, J., Rother, M., Hu, X., Ermler, U. and Shima, S. Identification of HcgC as a SAM-dependent pyridinol methyltransferase in [Fe]-hydrogenase cofactor biosynthesis. Angew. Chem. Int. Ed. Engl. 55 (2016) 9648-9651. [PMID: 27391308]
2. Bai, L., Fujishiro, T., Huang, G., Koch, J., Takabayashi, A., Yokono, M., Tanaka, A., Xu, T., Hu, X., Ermler, U. and Shima, S. Towards artificial methanogenesis: biosynthesis of the [Fe]-hydrogenase cofactor and characterization of the semi-synthetic hydrogenase. Faraday Discuss 198 (2017) 37-58. [PMID: 28294213]
3. Schaupp, S., Arriaza-Gallardo, F.J., Pan, H.J., Kahnt, J., Angelidou, G., Paczia, N., Costa, K., Hu, X. and Shima, S. In vitro biosynthesis of the [Fe]-hydrogenase cofactor verifies the proposed biosynthetic precursors. Angew. Chem. Int. Ed. Engl. 61 (2022) e202200994. [PMID: 35286742]
Accepted name: nicotinate methyltransferase
Reaction: S-adenosyl-L-methionine + nicotinate = S-adenosyl-L-homocysteine + methyl nicotinate
Glossary: methyl nicotinate = nicitinic acid methyl ester
Other name(s): NaMT1
Systematic name: S-adenosyl-L-methionine:nicotinate O-methyltransferase
Comments: The enzyme has been charcterized from the plant Arabidopsis thaliana. The product, methyl nicotinate, is involved in the transport of nicotinate to different parts of the plant.
References:
1. Wu, R., Zhang, F., Liu, L., Li, W., Pichersky, E. and Wang, G. MeNA, controlled by reversible methylation of nicotinate, is an NAD precursor that undergoes long-distance transport in Arabidopsis. Mol. Plant 11 (2018) 1264-1277. [PMID: 30055263]
Accepted name: sialate 8-O-methyltransferase
Reaction: S-adenosyl-L-methionine + N-acetylneuraminate = S-adenosyl-L-homocysteine + N-acetyl-8-O-methyl-neuraminate
Other name(s): N-acetylneuraminate 8-O-methyltransferase
Systematic name: S-adenosyl-L-methionine:sialate-8-O-methyltransferase
Comments: The enzyme has been isolated from gonads of the starfish Asterias rubens. It methylates N-glycolylneuraminate with equal specificity. Oligosaccharides containing N-acetyl-α-neuraminyl-(2→3)-β-D-galactosyl-(1→3)-N-acetyl-D-galactosyl structures are also methylated.
References:
1. Bergwerff, A.A., Hulleman, S.H., Kamerling, J.P., Vliegenthart, J.F., Shaw, L., Reuter, G. and Schauer, R. Nature and biosynthesis of sialic acids in the starfish Asterias rubens. Identification of sialo-oligomers and detection of S-adenosyl-L-methionine: N-acylneuraminate 8-O-methyltransferase and CMP-N-acetylneuraminate monooxygenase activities. Biochimie 74 (1992) 25-37. [PMID: 1576206]
2. Kelm, A., Shaw, L., Schauer, R. and Reuter, G. The biosynthesis of 8-O-methylated sialic acids in the starfish Asterias rubens—isolation and characterisation of S-adenosyl-L-methionine:sialate-8-O-methyltransferase. Eur. J. Biochem. 251 (1998) 874-884. [PMID: 9490063]
Accepted name: methylecgonone synthase
Reaction: S-adenosyl L-methionine + ecgonone = S-adenosyl-L-homocysteine + ecgonone methyl ester
For diagram of reaction click here.
Glossary: ecgonone = (1R,2R,5S)-8-methyl-3-oxo-8-azabicyclo[3.2.1]octane-2-carboxylate
Other name(s): MT4
Systematic name: S-adenosyl-L-methionine:ecgonone O-methyltransferase
Comments: Isolated from the plant Erythroxylum novogranatense. The enzyme, which is highly stereoselective, is involved in cocaine biosynthesis. The substrate, ecgonone, is unstable, and in the absence of the methyltransferase decarboxylates into tropinone.
References:
1. Wang, Y.J., Huang, J.P., Tian, T., Yan, Y., Chen, Y., Yang, J., Chen, J., Gu, Y.C. and Huang, S.X. Discovery and engineering of the cocaine biosynthetic pathway. J. Am. Chem. Soc. 144 (2022) 22000-22007. [PMID: 36376019]
Accepted name: long-chain-alcohol O-fatty-acyltransferase
Reaction: acyl-CoA + a long-chain alcohol = CoA + a long-chain alcohol wax ester
Other name(s): wax synthase (ambiguous); wax-ester synthase (ambiguous)
Systematic name: acyl-CoA:long-chain-alcohol O-acyltransferase
Comments: The enzyme transfers acyl residues from acyl-CoA to long-chain alcohols, forming wax esters. Wax esters have diverse biological functions in bacteria, insects, mammals, and terrestrial plants. The enzyme from the plant Simmondsia chinensis (jojoba) prefers acyl residues of chain-length C18 to C20 and its preferred acceptor is (11Z)-icos-11-en-1-ol. cf. EC 2.3.1.332, medium-chain-alcohol O-fatty-acyltransferase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 64060-40-8
References:
1. Wu, X.-Y., Moreau, R.A. and Stumpf, P.K. Studies of biosynthesis of waxes by developing jojoba seed. 3. Biosynthesis of wax esters from acyl-CoA and long-chain alcohols. Lipids 16 (1981) 897-902.
2. Uthoff, S., Stoveken, T., Weber, N., Vosmann, K., Klein, E., Kalscheuer, R. and Steinbuchel, A. Thio wax ester biosynthesis utilizing the unspecific bifunctional wax ester synthase/acyl coenzyme A:diacylglycerol acyltransferase of Acinetobacter sp. strain ADP1. Appl. Environ. Microbiol. 71 (2005) 790-796. [PMID: 15691932]
3. Teerawanichpan, P. and Qiu, X. Fatty acyl-CoA reductase and wax synthase from Euglena gracilis in the biosynthesis of medium-chain wax esters. Lipids 45 (2010) 263-273. [PMID: 20195781]
4. Tomiyama, T., Kurihara, K., Ogawa, T., Maruta, T., Ogawa, T., Ohta, D., Sawa, Y. and Ishikawa, T. Wax ester synthase/diacylglycerol acyltransferase isoenzymes play a pivotal role in wax ester biosynthesis in Euglena gracilis. Sci. Rep. 7 (2017) 13504. [PMID: 29044218]
Accepted name: isonitrile lipopeptide synthase
Reaction: 2 (3R)-3-isocyanobutanoyl-[acyl-carrier protein] + L-lysyl-[L-lysyl-carrier protein] + 2 NADPH = (3R)-N-[(2S)-1-hydroxy-6-[(3R)-3-isocyanobutanamido]hexan-2-yl]-3-isocyanobutanamide + [L-lysyl-carrier protein] + 2 [acyl-carrier protein] + 2 NADP+
Other name(s): scoA (gene name); mmaA (gene name)
Systematic name: (3R)-3-isocyano-fatty acyl-[acyl-carrier protein]:L-lysyl-[L-lysyl-carrier protein] (3R)-3-isocyano-fatty acyltransferase (hydrolysing)
Comments: The enzyme, found in some actinobacterial species, is a non-ribosomal peptide synthase (NRPS). Adenylation and thiolation domains of the enzyme activate a lysine residue and load it on the enzyme (this activity is described separately as EC 6.2.1.77, L-lysine—[L-lysyl-carrier protein] ligase). A condensation domain catalyses the condensation of two isonitrile-containing moieties to both amino groups of the lysine, a rare activity in non-ribosomal peptide biosynthesis. A reductase domain catalyses a four-electron reduction, releasing the product from the NRPS with a terminal alcohol group.
References:
1. Chhabra, A., Haque, A.S., Pal, R.K., Goyal, A., Rai, R., Joshi, S., Panjikar, S., Pasha, S., Sankaranarayanan, R. and Gokhale, R.S. Nonprocessive [2 + 2]e- off-loading reductase domains from mycobacterial nonribosomal peptide synthetases. Proc. Natl. Acad. Sci. USA 109 (2012) 5681-5686. [PMID: 22451903]
2. Harris, N.C., Sato, M., Herman, N.A., Twigg, F., Cai, W., Liu, J., Zhu, X., Downey, J., Khalaf, R., Martin, J., Koshino, H. and Zhang, W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc. Natl. Acad. Sci. USA 114 (2017) 7025-7030. [PMID: 28634299]
Accepted name: D-xylulose 5-phosphate:acyl-carrier protein glycolyltransferase system
Reaction: D-xylulose 5-phosphate + [acp] + a [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine = D-glyceraldehyde 3-phosphate + glycolyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine (overall reaction)
(1a) D-xylulose 5-phosphate + a [lipoyl-carrier protein]-N6-[(R)-lipoyl]-L-lysine = D-glyceraldehyde 3-phosphate + a [lipoyl-carrier protein]-N6-[glycolyl-(R)-dihydrolipoyl]-L-lysine
(1b) a [lipoyl-carrier protein]-N6-[glycolyl-(R)-dihydrolipoyl]-L-lysine + [acp] = glycolyl-[acp] + a [lipoyl-carrier protein]-N6-[(R)-dihydrolipoyl]-L-lysine
Other name(s): sclQ1/sclQ2/sclQ3 (gene names); napB/napD (gene names); QncN/QncL (gene names)
Systematic name: D-xylulose 5-phosphate:acyl-carrier protein glycolyltransferase
Comments: This enzyme system produces glycolyl-[acp] units that can be used by non-ribosomal peptide synthases. It catalyses a transketolase-like reaction on ketose phosphates derived from primary metabolism and transfers the resulting glycolyl moiety to a dedicated acyl-carrier protein. During the reaction cycle the glycolyl moiety is transferred first to a thiamine diphosphate cofactor, then to a lipoyl cofactor, and eventually to the acyl-carrier protein. While D-xylulose 5-phosphate is the best substrate, the enzyme can also accept D-fructose 6-phosphate and D-sedheptulose 7-phosphate. During the reaction the lipoyl cofactor is reduced to dihydrolipoyl, which must be oxidized back to lipoyl by an unknown enzyme.
References:
1. Peng, C., Pu, J.Y., Song, L.Q., Jian, X.H., Tang, M.C. and Tang, G.L. Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line. Proc. Natl. Acad. Sci. USA 109 (2012) 8540-8545. [PMID: 22586110]
2. Alberti, F., Leng, D.J., Wilkening, I., Song, L., Tosin, M. and Corre, C. Triggering the expression of a silent gene cluster from genetically intractable bacteria results in scleric acid discovery. Chem. Sci. 10 (2019) 453-463. [PMID: 30746093]
Accepted name: phenylglycine N-acetyltransferase
Reaction: acetyl-CoA + L-phenylglycine = (2S)-2-acetylamino-2-phenylacetic acid + CoA
Other name(s): natA (gene name)
Systematic name: acetyl-CoA:L-phenylgylcine N-acetyltransferase
Comments: The enzyme has been isolated from the bacterium Chryseobacterium sp. 5-3B. Reduced activity has been observed with L-2-phenylglycine methyl ester, L-2-chlorophenylglycine and L-4-hydroxyphenylglycine.
References:
1. Takenaka, S., Honma, Y., Yoshida, K. and Yoshida, K. Enantioselective N-acetylation of 2-phenylglycine by an unusual N-acetyltransferase from Chryseobacterium sp. Biotechnol. Lett. 35 (2013) 1053-1059. [PMID: 23479412]
2. Takenaka, S., Yoshida, K., Tanaka, K. and Yoshida, K. Molecular characterization of a novel N-acetyltransferase from Chryseobacterium sp. Appl. Environ. Microbiol. 80 (2014) 1770-1776. [PMID: 24375143]
3. Takenaka, S., Ozeki, T., Tanaka, K. and Yoshida, K.I. Homology modeling and prediction of the amino acid residues participating in the transfer of acetyl-CoA to arylalkylamine by the N-acetyltransferase from Chryseobacterium sp. Biotechnol. Lett. 39 (2017) 1699-1707. [PMID: 28721586]
Accepted name: medium-chain-alcohol O-fatty-acyltransferase
Reaction: acyl-CoA + a medium-chain alcohol = CoA + a medium-chain alcohol wax ester
Other name(s): wax synthase (ambiguous); wax-ester synthase (ambiguous)
Systematic name: acyl-CoA:medium-chain-alcohol O-acyltransferase
Comments: The enzyme transfers an acyl group from an acyl-CoA to a medium-chain fatty alcohol, forming a wax ester. Wax esters have diverse biological functions in bacteria, insects, mammals, and terrestrial plants.The enzyme from the plant Petunia × hybrida prefers medium chain alcohols and saturated very long-chain acyl-CoAs. The human enzyme AWAT1 prefers decan-1-ol (C10) and has lower activity with C16, C18, and C20 alcohols. cf. EC 2.3.1.75, long-chain-alcohol O-fatty-acyltransferase.
References:
1. Turkish, A.R., Henneberry, A.L., Cromley, D., Padamsee, M., Oelkers, P., Bazzi, H., Christiano, A.M., Billheimer, J.T. and Sturley, S.L. Identification of two novel human acyl-CoA wax alcohol acyltransferases: members of the diacylglycerol acyltransferase 2 (DGAT2) gene superfamily. J. Biol. Chem. 280 (2005) 14755-14764. [PMID: 15671038]
2. King, A., Nam, J.W., Han, J., Hilliard, J. and Jaworski, J.G. Cuticular wax biosynthesis in petunia petals: cloning and characterization of an alcohol-acyltransferase that synthesizes wax-esters. Planta 226 (2007) 381-394. [PMID: 17323080]
Accepted name: 3-oxoglutarate synthase
Reaction: 2 malonyl-CoA + H2O = 3-oxoglutarate + 2 CoA + CO2
Other name(s): EnPKS1; EnPKS2; PcPYKS1; HsPKS4
Systematic name: malonyl-CoA:malonyl-CoA malonyltransferase (3-oxoglutarate-forming)
Comments: The enzyme has been isolated from the plants Erythroxylum novogranatense and Atropa belladonna, and is widely distributed in Solanaceae and Erythroxylaceae plants, where it is involved in the biosynthesis of tropane alkaloids. The enzyme has also been isolated from the club-moss Huperzia serrata, and by implication is likely present in other Lycopodiaceae plants, where it is involved in the biosynthesis of lycopodium alkaloids.
References:
1. Bedewitz, M.A., Jones, A.D., D'Auria, J.C. and Barry, C.S. Tropinone synthesis via an atypical polyketide synthase and P450-mediated cyclization. Nat. Commun. 9 (2018) 5281. [PMID: 30538251]
2. Huang, J.P., Fang, C., Ma, X., Wang, L., Yang, J., Luo, J., Yan, Y., Zhang, Y. and Huang, S.X. Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation. Nat. Commun. 10 (2019) 4036. [PMID: 31492848]
3. Wang, J., Zhang, Z.K., Jiang, F.F., Qi, B.W., Ding, N., Hnin, S.YY., Liu, X., Li, J., Wang, X.H., Tu, P.F., Abe, I., Morita, H. and Shi, S.P. Deciphering the biosynthetic mechanism of pelletierine in lycopodium alkaloid biosynthesis. Org. Lett. 22 (2020) 8725-8729. [PMID: 33104367]
4. Tian, T., Wang, Y.J., Huang, J.P., Li, J., Xu, B., Chen, Y., Wang, L., Yang, J., Yan, Y. and Huang, S.X. Catalytic innovation underlies independent recruitment of polyketide synthases in cocaine and hyoscyamine biosynthesis. Nat. Commun. 13 (2022) 4994. [PMID: 36008484]
Accepted name: cocaine synthase
Reaction: benzoyl-CoA + ecgonine methyl ester = CoA + cocaine
For diagram of reaction click here.
Systematic name: benzoyl-CoA:ecgonine methyl ester O-benzoyltransferase
Comments: Isolated from the plant Erythoxylum coca. Cinnamoyl-CoA can substitute for benzoyl-CoA.
References:
1. Schmidt, G.W., Jirschitzka, J., Porta, T., Reichelt, M., Luck, K., Torre, J.C., Dolke, F., Varesio, E., Hopfgartner, G., Gershenzon, J. and D'Auria, J.C. The last step in cocaine biosynthesis is catalyzed by a BAHD acyltransferase. Plant Physiol. 167 (2015) 89-101. [PMID: 25406120]
Accepted name: ribostamycin 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoate transferase
Reaction: 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] + ribostamycin = [BtrI acyl-carrier protein] + γ-L-glutamyl-butirosin B
Other name(s): btrH (gene name); ribostamycin:4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein] 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoate transferase
Systematic name: 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoyl-[BtrI acyl-carrier protein]:ribostamycin 4-(γ-L-glutamylamino)-(S)-2-hydroxybutanoate transferase
Comments: The enzyme attaches the side chain of the aminoglycoside antibiotics of the butirosin family. The side chain confers resistance against several aminoglycoside-modifying enzymes.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Llewellyn, N.M., Li, Y. and Spencer, J.B. Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain. Chem. Biol. 14 (2007) 379-386. [PMID: 17462573]
Accepted name: N-acetylneuraminylgalactosylglucosyl-glucoside β-1,4-N-acetylgalactosaminyltransferase
Reaction: UDP-N-acetyl-α-D-galactosamine + an α-N-acetylneuraminyl-(2→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-R = UDP + an N-acetyl-β-D-galactosaminyl-(1→4)-[α-N-acetylneuraminyl-(2→3)]-β-D-galactosyl-(1→4)-β-D-glucosyl-R
Other name(s): B4GALNT2 (gene name); uridine diphosphoacetylgalactosamine-acetylneuraminyl(α2→3)galactosyl(β1→4)glucosyl β1→4-acetylgalactosaminyltransferase; UDP-N-acetyl-D-galactosamine:N-acetylneuraminyl-2,3-α-D-galactosyl-1,4-β-D-glucosylceramide β-1,4-N-acetylgalactosaminyltransferase (incorrect); UDP-N-acetyl-D-galactosamine:N-acetylneuraminyl-(2→3)-α-D-galactosyl-(1→4)-β-D-glucosyl(1↔1)ceramide 4-β-N-acetylgalactosaminyltransferase (incorrect); UDP-N-acetyl-D-galactosamine:N-acetylneuraminyl-(2→3)-α-D-galactosyl-(1→4)-β-D-glucosyl-(1↔1)-ceramide 4-β-N-acetylgalactosaminyltransferase (incorrect); N-acetylneuraminylgalactosylglucosylceramide β-1,4-N-acetylgalactosaminyltransferase (incorrect)
Systematic name: UDP-N-acetyl-α-D-galactosamine:α-N-acetylneuraminyl-(2→3)-β-D-galactosyl-(1→4)-β-D-glucosyl-R 4-β-N-acetylgalactosaminyltransferase
Comments: Requires Mn2+. The enzyme, found in mammals, is only active with substrates containing (2→3) linked sialic acid residues [2,3]. It is active with glycoproteins, but not with gangliosides. The enzyme is involved in synthesis of the blood group antigen Sda.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 109136-50-7
References:
1. Piller, F., Blanchard, D., Huet, M. and Cartron, J.-P. Identification of a α-NeuAc-(2-3)-β-D-galactopyranosyl N-acetyl-β-D-galactosaminyltransferase in human kidney. Carbohydr. Res. 149 (1986) 171-184. [PMID: 2425965]
2. Takeya, A., Hosomi, O. and Kogure, T. Identification and characterization of UDP-GalNAc: NeuAc α2-3Gal β1-4Glc(NAc) β1-4(GalNAc to Gal)N-acetylgalactosaminyltransferase in human blood plasma. J. Biochem. (Tokyo) 101 (1987) 251-259. [PMID: 3106337]
3. Dohi, T., Nishikawa, A., Ishizuka, I., Totani, M., Yamaguchi, K., Nakagawa, K., Saitoh, O., Ohshiba, S. and Oshima, M. Substrate specificity and distribution of UDP-GalNAc:sialylparagloboside N-acetylgalactosaminyltransferase in the human stomach. Biochem. J. 288 (1992) 161-165. [PMID: 1445260]
4. Montiel, M.D., Krzewinski-Recchi, M.A., Delannoy, P. and Harduin-Lepers, A. Molecular cloning, gene organization and expression of the human UDP-GalNAc:Neu5Acα2-3Galβ-R β1,4-N-acetylgalactosaminyltransferase responsible for the biosynthesis of the blood group Sda/Cad antigen: evidence for an unusual extended cytoplasmic domain. Biochem. J. 373 (2003) 369-379. [PMID: 12678917]
Accepted name: phenyllactate glucosyltransferase
Reaction: UDP-α-D-glucose + (R)-3-(phenyl)lactate = UDP + (R)-(phenyl)lactyl-β-D-glucose
For diagram of reaction click here.
Other name(s): UGT1
Systematic name: UDP-α-D-glucose:(R)-3-(phenyl)lactate O-β-D-glucosyltransferase
Comments: Isolated from the plant Atropa belladonna (deadly nightshade). Involved in the biosynthesis of littorine
References:
1. Qiu, F., Zeng, J., Wang, J., Huang, J.P., Zhou, W., Yang, C., Lan, X., Chen, M., Huang, S.X., Kai, G. and Liao, Z. Functional genomics analysis reveals two novel genes required for littorine biosynthesis. New Phytol. 225 (2020) 1906-1914. [PMID: 31705812]
Accepted name: littorine synthase
Reaction: (R)-phenyllactyl-β-D-glucose + tropine = D-glucose + littorine
For diagram of reaction click here.
Glossary: tropine = (3-endo)-8-methyl-8-azabicyclo[3.2.1]octan-3-ol
littorine = 8-methyl-8-azabicyclo[3.2.1]oct-3-yl (2R)-2-hydroxy-3-phenylpropanoate
Other name(s): LS (gene name)
Systematic name: (R)-phenyllactyl-β-D-glucose:tropine O-D-glucosyltransferase (littorine forming)
Comments: Isolated from the plant Atropa belladonna (deadly nightshade). Involved in the biosynthesis of the alkaloid L-hyoscyamine (S-atropine).
References:
1. Qiu, F., Zeng, J., Wang, J., Huang, J.P., Zhou, W., Yang, C., Lan, X., Chen, M., Huang, S.X., Kai, G. and Liao, Z. Functional genomics analysis reveals two novel genes required for littorine biosynthesis. New Phytol. 225 (2020) 1906-1914. [PMID: 31705812]
Accepted name: spermidine—8-amino-7-oxononanoate transaminase
Reaction: spermidine + 8-amino-7-oxononanoate = N-(3-aminopropyl)-4-aminobutanal + 7,8-diaminononanoate
Other name(s): BIO3-BIO1 (gene name)
Systematic name: spermidine:8-amino-7-oxononanoate aminotransferase
Comments: A pyridoxal 5′-phosphate enzyme. The enzyme, characterized from the plant Arabidopsis thaliana, differs from enzymes that catalyse a similar reaction by using spermidine as the amino group donor. The enzyme from Arabidopsis thaliana is bifunctional and also catalyses EC 6.3.3.3, dethiobiotin synthase. cf. EC 2.6.1.62, adenosylmethionine—8-amino-7-oxononanoate transaminase, and EC 2.6.1.105, lysine—8-amino-7-oxononanoate transaminase
References:
1. Noble, C.G., Hollinshead, T., Kende, A., Langford, M.P., Lim, P.P., Linney, E., Mattocks, J., Swindale, L.Y. and Green, K. The plant Diaminopelargonic acid aminotransferase uses spermidine as its amino donor. Plant J. 121 (2025) e70076. [PMID: 40028677]
Accepted name: pyridinol guanylyltransferase
Reaction: GTP + 6-carboxymethyl-3,5-dimethyl-4-hydroxypyridin-2-ol = guanylylpyridinol + diphosphate
Glossary: guanylylpyridinol = [4-(5′-guanylyloxy)-6-hydroxy-3,5-dimethylpyridin-2-yl]acetate
Other name(s): hcgB (gene name)
Systematic name: GTP:6-carboxymethyl-3,5-dimethyl-4-hydroxypyridin-2-ol guanylyltransferase
Comments: The enzyme, characterized from the archaeon Methanococcus maripaludis, participates in the biosynthesis of the iron-guanylylpyridinol (FeGP) cofactor of EC 1.12.98.2, 5,10-methenyltetrahydromethanopterin hydrogenase (also known as [Fe]-hydrogenase).
References:
1. Fujishiro, T., Tamura, H., Schick, M., Kahnt, J., Xie, X., Ermler, U. and Shima, S. Identification of the HcgB enzyme in [Fe]-hydrogenase-cofactor biosynthesis. Angew. Chem. Int. Ed. Engl. 52 (2013) 12555-12558. [PMID: 24249552]
2. Bai, L., Fujishiro, T., Huang, G., Koch, J., Takabayashi, A., Yokono, M., Tanaka, A., Xu, T., Hu, X., Ermler, U. and Shima, S. Towards artificial methanogenesis: biosynthesis of the [Fe]-hydrogenase cofactor and characterization of the semi-synthetic hydrogenase. Faraday Discuss 198 (2017) 37-58. [PMID: 28294213]
Accepted name: guanylylpyridinol adenylase
Reaction: ATP + guanylylpyridinol = guanylylpyridinol adenylate + diphosphate
Glossary: guanylylpyridinol = [4-(5′-guanylyloxy)-6-hydroxy-3,5-dimethylpyridin-2-yl]acetate
Other name(s): hcgE (gene name)
Systematic name: ATP:[4-(5′-guanylyloxy)-6-hydroxy-3,5-dimethylpyridin-2-yl]acetate adenylyltransferase
Comments: The enzyme, characterized from the archaeon Methanothermobacter marburgensis, participates in the biosynthesis of the iron-guanylylpyridinol (FeGP) cofactor of EC 1.12.98.2, 5,10-methenyltetrahydromethanopterin hydrogenase (also known as [Fe]-hydrogenase).
References:
1. Fujishiro, T., Kahnt, J., Ermler, U. and Shima, S. Protein-pyridinol thioester precursor for biosynthesis of the organometallic acyl-iron ligand in [Fe]-hydrogenase cofactor. Nat. Commun. 6 (2015) 6895. [PMID: 25882909]
Accepted name: ceramide phosphoethanolamine synthase
Reaction: (1) CDP-ethanolamine + a ceramide = a ceramide phosphorylethanolamine + CMP
(2) a phosphatidylethanolamine + a ceramide = a ceramide phosphorylethanolamine + a 1,2-diacyl-sn-glycerol
Other name(s): CPE synthase; Cpes (gene name); SGMS1 (gene name); SGMS2 (gene name); SAMD8 (gene name)
Systematic name: CDP-ethanolamine:ceramide phosphoethanolaminyltransferase
Comments: The enzyme from invertebrates, best studied from the fly Drosophila melanogaster, is common in arthropods, worms, bees, spiders, and scorpions, and has also been reported in deep-sea mussels and some sea snails, as well as protozoans and oomycetes. Its product, ceramide phosphoethanolamine, is the main sphingolipid in cell membranes of arthropods, such as Drosophila and Musca. The invertebrate enzyme requires a Mn(II) cofactor. In mammals the activity has been shown to be catalysed by members of the EC 2.7.8.27, sphingomyelin synthase, family, such as SGMS1, SGMS2, and SAMD8.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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. Ternes, P., Brouwers, J.F., van den Dikkenberg, J. and Holthuis, J.C. Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase. J. Lipid Res. 50 (2009) 2270-2277. [PMID: 19454763]
3. 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]
4. Kol, M., Panatala, R., Nordmann, M., Swart, L., van Suijlekom, L., Cabukusta, B., Hilderink, A., Grabietz, T., Mina, J.GM., Somerharju, P., Korneev, S., Tafesse, F.G. and Holthuis, J.CM. Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site-engineering of sphingomyelin synthases. J. Lipid Res. 58 (2017) 962-973. [PMID: 28336574]
5. Suzuki, R., Murakami, C., Dilimulati, K., Atsuta-Tsunoda, K., Kawai, T. and Sakane, F. Human sphingomyelin synthase 1 generates diacylglycerol in the presence and absence of ceramide via multiple enzymatic activities. FEBS Lett. 597 (2023) 2672-2686. [PMID: 37715942]
Accepted name: [Src-family] C-terminal protein kinase
Reaction: ATP + [a protein]-(L-tyrosine) = ADP + [a protein]-(L-tyrosine)-phosphate. The optimal peptide substrate contains the sequence (relative to the phosphorylated tyrosine: Glu-Glu-Asp/Glu-Ile-Tyr-Phe-Phe-Phe-Phe [1]. Physiological substrates are C-terminal tail of Src-family protein kinases [1].
Other name(s): C-terminal Src kinase; CSK (human gene name); Tyrosine-protein kinase CSK
Systematic name: ATP:[protein]-L-tyrosine O-phosphotransferase (Src-specific)
Comments: Requires Mg2+. Specifically phosphorylates a C-terminal tyrosine in Src family of non-receptor protein kinases (Tyr 527 chicken c-Src numbering, Tyr 530 human c-Src numbering) [1,2]. The enzyme engages in particular binding mode with its substrate proteins to present the C-terminal sequence in the active site. A shortened activation loop disrupts the conventional substrate peptide docking observed in most tyrosine kinases [1]. It can be activated by docking of the SH2 and linking regions to the kinase domain [3]. Removal of the SH3/SH2 domain decreases kinase activity by 100-fold [4]. Phosphorylation of Ser364 by cAMP-dependent protein kinase (EC 2.7.11.1) activates the enzyme in the presence of the Csk SH3 domain [5]. The SH3 domain lacks a tyrosine for autophosphorylation in its activation loop and requires a specific binding mode to its substrate proteins for catalysis [6].
References:
1. Sondhi, D., Xu, W., Songyang, Z., Eck, M.J. and Cole, P.A. Peptide and protein phosphorylation by protein tyrosine kinase Csk: insights into specificity and mechanism. Biochemistry 37 (1998) 165-172. [PMID: 9425036]
2. Nada, S., Okada, M., MacAuley, A., Cooper, J.A. and Nakagawa, H. Cloning of a complementary DNA for a protein-tyrosine kinase that specifically phosphorylates a negative regulatory site of p60c-src. Nature 351 (1991) 69-72. [PMID: 1709258]
3. Ogawa, A., Takayama, Y., Sakai, H., Chong, K.T., Takeuchi, S., Nakagawa, A., Nada, S., Okada, M. and Tsukihara, T. Structure of the carboxyl-terminal Src kinase, Csk. J. Biol. Chem. 277 (2002) 14351-14354. [PMID: 11884384]
4. Sondhi, D. and Cole, P.A. Domain interactions in protein tyrosine kinase Csk. Biochemistry 38 (1999) 11147-11155. [PMID: 10460171]
5. Yaqub, S., Abrahamsen, H., Zimmerman, B., Kholod, N., Torgersen, K.M., Mustelin, T., Herberg, F.W., Tasken, K. and Vang, T. Activation of C-terminal Src kinase (Csk) by phosphorylation at serine-364 depends on the Csk-Src homology 3 domain. Biochem. J. 372 (2003) 271-278. [PMID: 12600271]
6. Levinson, N.M., Seeliger, M.A., Cole, P.A. and Kuriyan, J. Structural basis for the recognition of c-Src by its inactivator Csk. Cell 134 (2008) 124-134. [PMID: 18614016]
Accepted name: ellagitannin acyl hydrolase
Reaction: punicalagin = punicalin + ellagic acid (overall reaction)
(1a) punicalagin + 2 H2O = punicalin + 4,4′,5,5′,6,6′-hexahydroxydiphenic acid
(1b) 4,4′,5,5′,6,6′-hexahydroxydiphenic acid = ellagic acid + 2 H2O (spontaneous)
For diagram of reaction click here
Other name(s): ellagitannase; ellagitannin acyl esterase; EAH
Systematic name: punicalagin acyl hydrolase
Comments: The enzyme, which has been studied from the fungus Aspergillus niger, catalyses a step in the degradation of ellagitannins such as punicalagin, which are phenolic compounds occurring in pomegranates and some tropical trees. It hydrolyses ester bonds between the D-glucose core and the hexahydroxydiphenic acid groups of ellagitannins, releasing hexahydroxydiphenic acid that undergoes spontaneous lactonization to form ellagic acid. Unlike EC 3.1.1.20, tannase, it does not act on gallotannins. More recent studies suggest that the activity may be catalysed by EC 3.1.4.3, phospholipase C [5].
References:
1. Ascacio-Valdes, J.A., Buenrostro, J.J., De la Cruz, R., Sepulveda, L., Aguilera, A.F., Prado, A., Contreras, J.C., Rodriguez, R. and Aguilar, C.N. Fungal biodegradation of pomegranate ellagitannins. J. Basic Microbiol. 54 (2014) 28-34. [PMID: 23564673]
2. de la Cruz, R., Ascacio, J.A., Buenrostro, J., Sepulveda, L., Rodriguez, R., Prado-Barragan, A., Contreras, J.C., Aguilera, A. and Aguilar, C.N. Optimization of ellagitannase production by Aspergillus niger GH1 by solid-state fermentation. Prep Biochem Biotechnol 45 (2015) 617-631. [PMID: 25085574]
3. Ascacio-Valdes, J.A., Aguilera-Carbo, A.F., Buenrostro, J.J., Prado-Barragan, A., Rodriguez-Herrera, R. and Aguilar, C.N. The complete biodegradation pathway of ellagitannins by Aspergillus niger in solid-state fermentation. J. Basic Microbiol. 56 (2016) 329-336. [PMID: 26915983]
4. Buenrostro-Figueroa, J., Mireles, M., Ascacio-Valdes, J.A., Aguilera-Carbo, A., Sepulveda, L., Contreras-Esquivel, J., Rodriguez-Herrera, R. and, N. Aguilar, C. Enzymatic biotransformation of pomegranate ellagitannins: initial approach to reaction conditions. Iran. J. Biotechnol. 18 (2020) e2305. [PMID: 33542933]
5. Buenrostro-Figueroa, J., Gutierrez-Sanchez, G., Prado-Barragan, L.A., Rodriguez-Herrera, R., Aguilar-Zarate, P., Sepulveda, L., Ascacio-Valdes, J.A., Tafolla-Arellano, J.C. and Aguilar, C.N. Influence of culture conditions on ellagitannase expression and fungal ellagitannin degradation. Bioresour. Technol. 337 (2021) 125462. [PMID: 34320742]
Accepted name: phosphatidylethanolamine phospholipase C
Reaction: a phosphatidylethanolamine + H2O = a 1,2-diacyl-sn-glycerol + O-phosphoethanolamine
Other name(s): phosphatidylethanolamine-specific phospholipase C; PE-PLC; SMSr; SAMD8 (gene name); SMS1 (gene name)
Systematic name: phosphatidylethanolamine ethanolaminephosphohydrolase
Comments: This activity, which is similar to that of EC 3.1.4.3, phospholipase C, has been characterized from mammalian cells [1-4]. Multiple enzymes have been shown to catalyse this activity, including human sphingomyelin synthase-related protein (SMSr, gene name; SAMD8) [6-8] and sphingomyelin synthase 1 (SMS1, gene name; SGMS1) [9] (cf. EC 2.7.8.27, sphingomyelin synthase). Minor activity was also observed by sphingomyelin synthase 2 (SMS2, gene name; SGMS2) [10].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
References:
1. Hafez, M.M. and Costlow, M.E. Phosphatidylethanolamine turnover is an early event in the response of NB2 lymphoma cells to prolactin. Exp. Cell Res. 184 (1989) 37-43. [PMID: 2507337]
2. Kiss, Z. and Anderson, W.B. ATP stimulates the hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. Potentiating effects of guanosine triphosphates and sphingosine. J. Biol. Chem. 265 (1990) 7345-7350. [PMID: 2185245]
3. Kiss, Z., Crilly, K. and Chattopadhyay, J. Ethanol potentiates the stimulatory effects of phorbol ester, sphingosine and 4-hydroxynonenal on the hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. Eur. J. Biochem. 197 (1991) 785-790. [PMID: 2029907]
4. Kiss, Z. The long-term combined stimulatory effects of ethanol and phorbol ester on phosphatidylethanolamine hydrolysis are mediated by a phospholipase C and prevented by overexpressed α-protein kinase C in fibroblasts. Eur. J. Biochem. 209 (1992) 467-473. [PMID: 1327780]
5. Kiss, Z. and Tomono, M. Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis. Biochim. Biophys Acta 1259 (1995) 105-108. [PMID: 7492608]
6. Murakami, C. and Sakane, F. Sphingomyelin synthase-related protein generates diacylglycerol via the hydrolysis of glycerophospholipids in the absence of ceramide. J. Biol. Chem. 296 (2021) 100454. [PMID: 33621517]
7. Chiang, Y.P., Li, Z., Chen, Y., Cao, Y. and Jiang, X.C. Sphingomyelin synthase related protein is a mammalian phosphatidylethanolamine phospholipase C. Biochim Biophys Acta Mol Cell Biol Lipids 1866 (2021) 159017. [PMID: 34332077]
8. Hu, K., Zhang, Q., Chen, Y., Yang, J., Xia, Y., Rao, B., Li, S., Shen, Y., Cao, M., Lu, H., Qin, A., Jiang, X.C., Yao, D., Zhao, J., Zhou, L. and Cao, Y. Cryo-EM structure of human sphingomyelin synthase and its mechanistic implications for sphingomyelin synthesis. Nat. Struct. Mol. Biol. (2024) . [PMID: 38388831]
9. Suzuki, R., Murakami, C., Dilimulati, K., Atsuta-Tsunoda, K., Kawai, T. and Sakane, F. Human sphingomyelin synthase 1 generates diacylglycerol in the presence and absence of ceramide via multiple enzymatic activities. FEBS Lett. 597 (2023) 2672-2686. [PMID: 37715942]
10. Murakami, C., Dilimulati, K., Atsuta-Tsunoda, K., Kawai, T., Inomata, S., Hijikata, Y., Sakai, H. and Sakane, F. Multiple activities of sphingomyelin synthase 2 generate saturated fatty acid- and/or monounsaturated fatty acid-containing diacylglycerol. J. Biol. Chem. 300 (2024) 107960. [PMID: 39510177]
Accepted name: chitinosanase
Reaction: Xm-(1→4)-β-D-GlcpN-(1→4)-β-D-GlcpNAc-(1→4)-Xn + H2O = Xm-(1→4)-β-D-GlcpN-(1→4)-α-D-GlcpNAc + Xn
Glossary: X = [→4)-β-D-GlcpN/GlcNAc-(1→]; m > 1; n ≥ 0
Other name(s): chitosan hydrolase (ambiguous)
Systematic name: partially acetylated chitosan endo glucsamino-N-acetylglucosaminohydrolase (configuration-inverting)
Comments: The enzyme is an endo hydrolase that cleaves after the GlcN-GlcNAc diad in partially acetylated chitosan with subsite -2 specific for GlcN and subsite -1 specific for GlcNAc. The enzyme does not cleave fully deacetylated chitosans which are cleaved by chitosanases (EC 3.2.1.132) and glucosaminidases (EC 3.2.1.165) or fully acetylated chitins which are cleaved by chitinases (EC 3.2.1.14, EC 3.2.1.200, EC 3.2.1.201, EC 3.2.1.202) and N-acetylglucosaminidases (EC 3.2.1.52). The protein was found in the medium in which the plant pathogenic fungus Alternaria alternata was grown.
References:
1. Kohlhoff, M., Niehues, A., Wattjes, J., Beneteau, J., Cord-Landwehr, S., El Gueddari, N.E., Bernard, F., Rivera-Rodriguez, G.R. and Moerschbacher, B.M. Chitinosanase: A fungal chitosan hydrolyzing enzyme with a new and unusually specific cleavage pattern. Carbohydr. Polym. 174 (2017) 1121-1128. [PMID: 28821036]
Accepted name: activated protein C (thrombin-activated peptidase)
Reaction: Degradation of blood coagulation factors Va and VIIIa
Other name(s): blood-coagulation factor XIVa; activated blood coagulation factor XIV; activated protein C; autoprothrombin II-A; protein Ca; APC; GSAPC; protein C (activated)
Comments: A peptidase of family S1 (trypsin family), one of the γ-carboxyglutamic acid-containing coagulation factors. The enzyme plays an important role in regulating anticoagulation, inflammation, and cell death by proteolytically inactivating the blood coagulation factors factor Va and factor VIIIa. Formed from protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin. Protein C can also be activated by serine endopeptidases present in several snake venoms.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, MEROPS, PDB, CAS registry number: 42617-41-4
References:
1. Esmon, C.T. The regulation of natural anticoagulant pathways. Science 235 (1987) 1348-1352. [PMID: 3029867]
2. Esmon, C.T. The roles of protein C and thrombomodulin in the regulation of blood coagulation. J. Biol. Chem. 264 (1989) 4743-4746. [PMID: 2538457]
Accepted name: 2-deoxy-4-epi-scyllo-inosose synthase
Reaction: D-mannose 6-phosphate = 2-deoxy-4-epi-scyllo-inosose + phosphate
Glossary: 2-deoxy-4-epi-scyllo-inosose = (2R,3S,4S,5S)-2,3,4,5-tetrahydroxycyclohexan-1-one
Other name(s): eboD (gene name)
Systematic name: D-mannose-6-phosphate phosphate-lyase (2-deoxy-4-epi-scyllo-inosose-forming)
Comments: Requires Co2+ or Ni2+. The enzyme has been characterized from the cyanobacterium Nostoc punctiforme and the Gram-negative cellulose degrading bacterium Sporocytophaga myxococcoides. cf. EC 4.2.3.124, 2-deoxy-scyllo-inosose synthase
References:
1. Tanoeyadi, S., Zhou, W., Osborn, A.R., Tsunoda, T., Samadi, A., Burade, S., Waldo, T.J., Higgins, M.A. and Mahmud, T. 2-Deoxy-4-epi-scyllo-inosose (DEI) is the product of EboD, a highly conserved dehydroquinate synthase-like enzyme in bacteria and eustigmatophyte algae. ACS Chem. Biol. 19 (2024) 2277-2283. [PMID: 39404639]
Accepted name: intrinsic cysteine-dependent pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase
Reaction: (1) [LarE]-L-cysteine + pyridin-1-ium-3,5-dicarboxylate mononucleotide + ATP = [LarE]-dehydroalanine + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + AMP + diphosphate (overall reaction)
(1a) ATP + pyridin-1-ium-3,5-dicarboxylate mononucleotide = diphosphate + 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate
(1b) 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate + [LarE]-L-cysteine = AMP + [LarE]-S-[5-carboxy-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl]-L-cysteine
(1c) [LarE]-S-[5-carboxy-1-(5-O-phosphono-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl]-L-cysteine = [LarE]-dehydroalanine + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide
(2) [LarE]-L-cysteine + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + ATP = [LarE]-dehydroalanine + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide + AMP + diphosphate (overall reaction)
(2a) ATP + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide = diphosphate + 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate
(2b) 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate + [LarE]-L-cysteine = AMP + [LarE]-S-[1-(5-O-phosphono-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl]-L-cysteine
(2c) [LarE]-S-[1-(5-O-phosphono-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl]-L-cysteine = [LarE]-dehydroalanine + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide
Other name(s): LarE (ambiguous); P2CMN sulfurtransferase (ambiguous); pyridinium-3,5-biscarboxylic acid mononucleotide sulfurtransferase (ambiguous); P2TMN synthase (ambiguous); pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase (ambiguous)
Systematic name: [LarE]-S-[1-(5-O-phosphono-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl]-L-cysteine pyridin-1-ium-3,5-dicarbothioate-mononucleotide-lyase (ATP-consuming)
Comments: This enzyme, found in Lactobacillus plantarum, is involved in the biosynthesis of a nickel-pincer cofactor. The process starts when one enzyme molecule adenylates pyridinium-3,5-dicarboxylate mononucleotide (P2CMN) and covalently binds the adenylated product to an intrinsic cysteine residue. Next, the enzyme cleaves the carbon-sulfur bond, liberating pyridinium-3-carboxylate-5-thiocarboxylate mononucleotide (PCTMN) and leaving a 2-aminoprop-2-enoate (dehydroalanine) residue attached to the protein. Since the cysteine residue is not regenerated in vivo, the enzyme is inactivated during the process. A second enzyme molecule then repeats the process with PCTMN, adenylating it and covalently binding it to the same cysteine residue, followed by liberation of pyridinium-3,5-bisthiocarboxylate mononucleotide (P2TMN) and the inactivation of the second enzyme molecule. cf. EC 4.4.1.45, extrinsic cysteine-dependent pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Desguin, B., Goffin, P., Viaene, E., Kleerebezem, M., Martin-Diaconescu, V., Maroney, M.J., Declercq, J.P., Soumillion, P. and Hols, P. Lactate racemase is a nickel-dependent enzyme activated by a widespread maturation system. Nat. Commun. 5 (2014) 3615. [PMID: 24710389]
2. Desguin, B., Soumillion, P., Hols, P. and Hausinger, R.P. Nickel-pincer cofactor biosynthesis involves LarB-catalyzed pyridinium carboxylation and LarE-dependent sacrificial sulfur insertion. Proc. Natl. Acad. Sci. USA 113 (2016) 5598-5603. [PMID: 27114550]
3. Fellner, M., Desguin, B., Hausinger, R.P. and Hu, J. Structural insights into the catalytic mechanism of a sacrificial sulfur insertase of the N-type ATP pyrophosphatase family, LarE. Proc. Natl. Acad. Sci. USA 114 (2017) 9074-9079. [PMID: 28784764]
Accepted name: 2-(S-pantetheinyl)-carbapenam-3-carboxylate synthase
Reaction: (1) pantetheine + (3S,5S)-carbapenam-3-carboxylate + S-adenosyl-L-methionine = (2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate + 5′-deoxyadenosine + L-methionine
(2) pantetheine + (5R)-carbapen-2-em-3-carboxylate + S-adenosyl-L-methionine = 6-desethyl-OA-6129 A + 5′-deoxyadenosine + L-methionine
Glossary: 6-desethyl-OA-6129 A = (5S)-3-[({2-[(2R)-2,4-dihydroxy-3,3-dimethylbutanamido]propanamido}ethyl)sulfanyl]-7-oxo-1-azabicyclo[3.2.0]oct-2-ene-2-carboxylate
Other name(s): thnL (gene name)
Systematic name: (2R,3R,5S)-2-(S-pantetheinyl)-carbapenam-3-carboxylate lyase
Comments: The enzyme uses radical SAM (AdoMet) chemistry to catalyse thioether bond formation between pantetheine and C-2 of the carbapenam precursors (3S,5S)-carbapenam-3-carboxylate or (5R)-carbapen-2-em-3-carboxylate, leading to formation of complex carbapenems. Contains a bound [4Fe-4S] cluster and hydroxocobalamin.
References:
1. Sinner, E.K., Li, R., Marous, D.R. and Townsend, C.A. ThnL, a B12-dependent radical S-adenosylmethionine enzyme, catalyzes thioether bond formation in carbapenem biosynthesis. Proc. Natl. Acad. Sci. USA 119 (2022) e2206494119. [PMID: 35969793]
Accepted name: extrinsic cysteine-dependent pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase
Reaction: (1) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3,5-dicarboxylate mononucleotide + ATP + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + AMP + diphosphate + acceptor (overall reaction)
(1a) ATP + pyridin-1-ium-3,5-dicarboxylate mononucleotide = diphosphate + 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate
(1b) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + 5-carboxy-1-(5-O-phospho-β-D-ribofuranosyl)pyridin-1-ium-3-carbonyl adenylate + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + AMP + acceptor
(2) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide + ATP + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide + AMP + diphosphate + acceptor (overall reaction)
(2a) ATP + pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide = diphosphate + 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate
(2b) a [4Fe-5S] iron-sulfur cluster linked by 3 L-cysteine residues + 1-(5-O-phospho-β-D-ribofuranosyl)-5-(sulfanylcarbonyl)pyridin-1-ium-3-carbonyl adenylate + reduced acceptor = a [4Fe-4S] iron-sulfur cluster linked by 3 L-cysteine residues + pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide + AMP + acceptor
Other name(s): larE (gene name)
Systematic name: pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide sufo-lyase
Comments: This enzyme, found in the bacterium Thermotoga maritima, catalyses two complex reactions during the biosynthesis of a nickel-pincer cofactor. The process starts with the adenylation of pyridin-1-ium-3,5-dicarboxylate mononucleotide (P2CMN), which is covalently bound to an intrinsic cysteine residue. Next, a [4Fe-4S] iron-sulfur cluster receives a sulfane sulfur from free L-cysteine via the action of EC 2.8.1.7, cysteine desulfurase, forming a temporary [4Fe-5S] cluster. The sulfur atom then attacks the activated substrate, resulting in formation of pyridin-1-ium-3-carboxylate-5-thiocarboxylate mononucleotide (PCTMN). The process repeats twice, with pyridin-1-ium-3,5-bisthiocarboxylate mononucleotide (P2TMN) being the final product. cf. EC 4.4.1.37, intrinsic cysteine-dependent pyridinium-3,5-bisthiocarboxylic acid mononucleotide synthase.
References:
1. Chatterjee, S., Parson, K.F., Ruotolo, B.T., McCracken, J., Hu, J. and Hausinger, R.P. Characterization of a [4Fe-4S]-dependent LarE sulfur insertase that facilitates nickel-pincer nucleotide cofactor biosynthesis in Thermotoga maritima. J. Biol. Chem. 298 (2022) 102131. [PMID: 35700827]
2. Zecchin, P., Pecqueur, L., Oltmanns, J., Velours, C., Schunemann, V., Fontecave, M. and Golinelli-Pimpaneau, B. Structure-based insights into the mechanism of [4Fe-4S]-dependent sulfur insertase LarE. Protein Sci. 33 (2024) e4874. [PMID: 38100250]
Accepted name: L-lysine—[L-lysyl-carrier protein] ligase
Reaction: ATP + L-lysine + [L-lysyl-carrier protein] = AMP + diphosphate + L-lysyl-[L-lysyl-carrier protein] (overall reaction)
(1a) ATP + L-lysine = diphosphate + (L-lysyl)adenylate
(1b) (L-lysyl)adenylate + [L-lysyl-carrier protein] = AMP + L-lysyl-[L-lysyl-carrier protein]
Other name(s): scoA (gene name)
Systematic name: L-lysine:[L-lysyl-carrier protein] ligase (AMP-forming)
Comments: The adenylation domain of the enzyme catalyses the activation of L-lysine to (L-lysyl)adenylate, followed by the transfer of the activated compound to the free thiol of a phosphopantetheine arm of a peptidyl-carrier protein domain. The peptidyl-carrier protein domain may be part of the same protein (as in the case of ScoA), or of a different protein. This activity is often found as part of a larger non-ribosomal peptide synthase.
References:
1. Harris, N.C., Sato, M., Herman, N.A., Twigg, F., Cai, W., Liu, J., Zhu, X., Downey, J., Khalaf, R., Martin, J., Koshino, H. and Zhang, W. Biosynthesis of isonitrile lipopeptides by conserved nonribosomal peptide synthetase gene clusters in Actinobacteria. Proc. Natl. Acad. Sci. USA 114 (2017) 7025-7030. [PMID: 28634299]
Accepted name: (3R)-β-phenylalanine—CoA ligase
Reaction: ATP + (3R)-β-phenylalanine + CoA = AMP + diphosphate + (3R)-β-phenylalanine-CoA (overall reaction)
(1a) ATP + (3R)-β-phenylalanine = diphosphate + (3R)-β-phenylalanineadenylate
(1b) (3R)-β-phenylalanineadenylate + CoA = AMP + (3R)-β-phenylalanine-CoA-CoA
For diagram of reaction click here
Other name(s): N7525_006484; β-phenylalanyl coenzyme A ligase; TAAE16 (gene name)
Systematic name: (3R)-β-phenylalanine:CoA ligase (AMP-forming)
Comments: The enzyme, characterized from the fungus Penicillium chrysogenum, acts on (3R)-β-phenylalanine and has slight activity on some other amino acids including (3S)-β-phenylalanine. It also acts on medium-chain-length alkanoic acids as EC 6.2.1.2 (medium-chain acyl-CoA ligase). In taxol-producing trees the enzyme is involved in taxol biosynthesis.
References:
1. Koetsier, M.J., Jekel, P.A., Wijma, H.J., Bovenberg, R.A. and Janssen, D.B. Aminoacyl-coenzyme A synthesis catalyzed by a CoA ligase from Penicillium chrysogenum. FEBS Lett. 585 (2011) 893-898. [PMID: 21334330]
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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:
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]
Accepted name: atromentin synthase
Reaction: 2 ATP + 2 3-(4-hydroxyphenyl)pyruvate = 2 AMP + 2 diphosphate + atromentin (overall reaction)
(1a) ATP + 3-(4-hydroxyphenyl)pyruvate + [atromentin synthase] = AMP + diphosphate + 3-(4-hydroxyphenyl)pyruvoyl-[atromentin synthase]
(1b) ATP + 3-(4-hydroxyphenyl)pyruvate + 3-(4-hydroxyphenyl)pyruvoyl-[atromentin synthase] = AMP + diphosphate + atromentin + [atromentin synthase]
For diagram of reaction click here.
Glossary: atromentin = 2,5-dihydroxy-3,6-bis(4-hydroxyphenyl)-1,4-benzoquinone
Other name(s): atromentin synthetase; invA1 (gene name); invA2 (gene name); invA5 (gene name); greA (gene name); atrA (gene name)
Systematic name: 3-(4-hydroxyphenyl)pyruvate:3-(4-hydroxyphenyl)pyruvate ligase (atromentin-forming)
Comments: Requires Mg2+.The enzyme, found in some fungi such as members of the Boletales and Eurotiales order, is a non-ribosomal peptide synthase-like enzyme comprising three domains - an adelylation (A) domain, an ayl-carrier protein (ACP) domain, and a thioesterase (TE) domain. The enzyme activates 3-(4-hydroxyphenyl)pyruvate by adenylation and catalyses the dimerization/cyclization of two such molecules to form atromentin. Atromentin is a precursor for assorted metabolites produced by the fungi, including pulvinic acids and 2,5-diarylcyclopentenones.
References:
1. Schneider, P., Bouhired, S. and Hoffmeister, D. Characterization of the atromentin biosynthesis genes and enzymes in the homobasidiomycete Tapinella panuoides. Fungal Genet. Biol. 45 (2008) 1487-1496. [PMID: 18805498]
2. Wackler, B., Lackner, G., Chooi, Y.H. and Hoffmeister, D. Characterization of the Suillus grevillei quinone synthetase GreA supports a nonribosomal code for aromatic α-keto acids. Chembiochem 13 (2012) 1798-1804. [PMID: 22730234]
3. Braesel, J., Gotze, S., Shah, F., Heine, D., Tauber, J., Hertweck, C., Tunlid, A., Stallforth, P. and Hoffmeister, D. Three redundant synthetases secure redox-active pigment production in the Basidiomycete Paxillus involutus. Chem. Biol. 22 (2015) 1325-1334. [PMID: 26496685]
Accepted name: polyporic acid synthase
Reaction: 2 ATP + 2 3-phenyl-2-oxopropanoate = 2 AMP + 2 diphosphate + polyporic acid (overall reaction)
(1a) ATP + 3-phenyl-2-oxopropanoate + [polyporic acid synthase] = AMP + diphosphate + 3-pheny-2-oxopropanoyl-[polyporic acid synthase]
(1b) ATP + 3-phenyl-2-oxopropanoate + 3-pheny-2-oxopropanoyl-[polyporic acid synthase] = AMP + diphosphate + polyporic acid + [polyporic acid synthase]
Glossary: polyporic acid = 2,5-dihydroxy-3,6-diphenylcyclohexa-2,5-diene-1,4-dione
3-phenyl-2-oxopropanoate = 3-phenylpyruvate
Other name(s): polyporic acid synthetase; corA (gene name); hapA1 (gene name); hapA2 (gene name)
Systematic name: 3-phenyl-2-oxopropanoate:3-phenyl-2-oxopropanoate ligase (polyporic acid-forming)
Comments: Requires Mg2+. The enzyme, found in mushrooms of the Basidiomycota and Ascomycota phyla, is a non-ribosomal peptide synthase-like enzyme comprising three domains - an adelylation (A) domain, an ayl-carrier protein (ACP) domain, and a thioesterase (TE) domain. The enzyme activates 3-phenyl-2-oxopropanoate by adenylation and catalyses the dimerization/cyclization of two such molecules to form polyporic acid. Polyporic acid is a precursor for assorted metabolites produced by the fungi, such as the corticins.
References:
1. Lawrinowitz, S., Wurlitzer, J.M., Weiss, D., Arndt, H.D., Kothe, E., Gressler, M. and Hoffmeister, D. Blue light-dependent pre-mRNA splicing controls pigment biosynthesis in the mushroom Terana caerulea. Microbiol. Spectr. 10 (2022) e0106522. [PMID: 36094086]
2. Seibold, P.S., Lawrinowitz, S., Raztsou, I., Gressler, M., Arndt, H.D., Stallforth, P. and Hoffmeister, D. Bifurcate evolution of quinone synthetases in basidiomycetes. Fungal Biol Biotechnol 10 (2023) 14. [PMID: 37400920]
Accepted name: didemethylasterriquinone D synthase
Reaction: 2 ATP + 2 (indol-3-yl)pyruvate = 2 AMP + 2 diphosphate + didemethylasterriquinone D (overall reaction)
(1a) ATP + (indol-3-yl)pyruvate + [didemethylasterriquinone D synthase] = AMP + diphosphate + (indol-3-yl)pyruvoyl-[didemethylasterriquinone D synthase]
(1b) ATP + (indol-3-yl)pyruvate + (indol-3-yl)pyruvoyl-[didemethylasterriquinone D synthase] = AMP + diphosphate + didemethylasterriquinone D + [didemethylasterriquinone D synthase]
Glossary: didemethylasterriquinone D = 3,6-dihydroxy-2,5-diindol-3′-yl-1,4-benzoquinone
Other name(s): didemethylasterriquinone D synthetase; tdiA (gene name)
Systematic name: (indol-3-yl)pyruvate:(indol-3-yl)pyruvate ligase (didemethylasterriquinone D-forming)
Comments: Requires Mg2+. The enzyme, characterized from the fungus Aspergillus nidulans, is a non-ribosomal peptide synthase-like enzyme comprising three domains - an adelylation (A) domain, an ayl-carrier protein (ACP) domain, and a thioesterase (TE) domain. The enzyme activates (indol-3-yl)pyruvate by adenylation and catalyses the dimerization/cyclization of two such molecules to form didemethylasterriquinone D. didemethylasterriquinone D is subsequently converted to terrequinone A, a cytotoxic compound that displays a broad range of bioactivities.
References:
1. Bok, J.W., Hoffmeister, D., Maggio-Hall, L.A., Murillo, R., Glasner, J.D. and Keller, N.P. Genomic mining for Aspergillus natural products. Chem. Biol. 13 (2006) 31-37. [PMID: 16426969]
2. Schneider, P., Weber, M., Rosenberger, K. and Hoffmeister, D. A one-pot chemoenzymatic synthesis for the universal precursor of antidiabetes and antiviral bis-indolylquinones. Chem. Biol. 14 (2007) 635-644. [PMID: 17584611]
3. Balibar, C.J., Howard-Jones, A.R. and Walsh, C.T. Terrequinone A biosynthesis through L-tryptophan oxidation, dimerization and bisprenylation. Nat. Chem. Biol. 3 (2007) 584-592. [PMID: 17704773]