An asterisk before "EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Accepted name: 4,4'-diapolycopenoate synthase
Reaction: (1) 4,4'-diapolycopen-4-al + H2O + acceptor = 4,4'-diapolycopen-4-oate + reduced acceptor
(2) 4,4'-diapolycopene-4,4'-dial + 2 H2O + 2 acceptor = 4,4'-diapolycopene-4,4'-dioate + 2 reduced acceptor
For diagram of reaction click here
Other name(s): crtNc; 4,4'-diapolycopenealdehyde oxidase (misleading)
Systematic name: 4,4'-diapolycopen-4-al,donor:oxygen oxidoreductase (4,4'-diapolycopen-4-oate-forming)
Comments: The enzyme has been described from the bacteria Methylomonas sp. 16a and Bacillus indicus.
References:
1. Tao, L., Schenzle, A., Odom, J.M. and Cheng, Q. Novel carotenoid oxidase involved in biosynthesis of 4,4'-diapolycopene dialdehyde. Appl. Environ. Microbiol. 71 (2005) 3294-3301. [PMID: 15933032]
2. Steiger, S., Perez-Fons, L., Cutting, S.M., Fraser, P.D. and Sandmann, G. Annotation and functional assignment of the genes for the C30 carotenoid pathways from the genomes of two bacteria: Bacillus indicus and Bacillus firmus. Microbiology 161 (2015) 194-202. [PMID: 25326460]
EC 1.3.1.113
Accepted name: (4-alkanoyl-5-oxo-2,5-dihydrofuran-3-yl)methyl phosphate reductase
Reaction: a [(3S)-4-alkanoyl-5-oxooxolan-3-yl]methyl phosphate + NADP+ = a (4-alkanoyl-5-oxo-2,5-dihydrofuran-3-yl)methyl phosphate + NADPH + H+
Other name(s): bprA (gene name); scbB (gene name)
Systematic name: [(3S)-4-alkanoyl-5-oxooxolan-3-yl]methyl phosphate:NADP+ oxidoreductase
Comments: The enzyme, characterized from the bacteria Streptomyces griseus and Streptomyces coelicolor, is involved in the biosynthesis of γ-butyrolactone autoregulators that control secondary metabolism and morphological development in Streptomyces bacteria.
References:
1. Kato, J.Y., Funa, N., Watanabe, H., Ohnishi, Y. and Horinouchi, S. Biosynthesis of γ-butyrolactone autoregulators that switch on secondary metabolism and morphological development in Streptomyces. Proc. Natl Acad. Sci. USA 104 (2007) 2378-2383. [PMID: 17277085]
EC 1.3.8.14
Accepted name: L-prolyl-S-[peptidyl-carrier protein] dehydrogenase
Reaction: S-(L-prolyl)-[peptidyl-carrier protein] + 2 electron-transfer flavoprotein = S-(1H-pyrrole-2-carbonyl)-[peptidyl-carrier protein] + 2 reduced electron-transfer flavoprotein
Other name(s): pigA (gene name); bmp3 (gene name); pltE (gene name); redW (gene name)
Systematic name: S-(L-prolyl)-[peptidyl-carrier protein]:electron-transfer flavoprotein oxidoreductase
Comments: Contains FAD. The enzyme participates in the biosynthesis of several pyrrole-containing compounds, such as undecylprodigiosin, prodigiosin, pyoluteorin, and coumermycin A1. It is believed to catalyse the formation of a Δ2-pyrrolin-2-yl(carbonyl)-S-[peptidyl-carrier protein] intermediate, followed by a two-electron oxidation to 1H-pyrrol-2-yl(carbonyl)-S-[peptidyl-carrier protein].
References:
1. Thomas, M.G., Burkart, M.D. and Walsh, C.T. Conversion of L-proline to pyrrolyl-2-carboxyl-S-PCP during undecylprodigiosin and pyoluteorin biosynthesis. Chem. Biol. 9 (2002) 171-184. [PMID: 11880032]
2. Harris, A.K., Williamson, N.R., Slater, H., Cox, A., Abbasi, S., Foulds, I., Simonsen, H.T., Leeper, F.J. and Salmond, G.P. The Serratia gene cluster encoding biosynthesis of the red antibiotic, prodigiosin, shows species- and strain-dependent genome context variation. Microbiology 150 (2004) 3547-3560. [PMID: 15528645]
*EC 1.8.5.4
Accepted name: bacterial sulfide:quinone reductase
Reaction: n HS- + n quinone = polysulfide + n quinol
Other name(s): sqr (gene name); sulfide:quinone reductase (ambiguous)
Systematic name: sulfide:quinone oxidoreductase
Comments: Contains FAD. Ubiquinone, plastoquinone or menaquinone can act as acceptor in different species. This enzyme catalyses the formation of sulfur globules. It repeats the catalytic cycle without releasing the product, producing a polysulfide of up to 10 sulfur atoms. The reaction stops when the maximum length of the polysulfide that can be accommodated in the sulfide oxidation pocket is achieved. The enzyme also plays an important role in anoxygenic bacterial photosynthesis. cf. EC 1.8.5.8, eukaryotic sulfide quinone oxidoreductase.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Arieli, B., Shahak, Y., Taglicht, D., Hauska, G. and Padan, E. Purification and characterization of sulfide-quinone reductase, a novel enzyme driving anoxygenic photosynthesis in Oscillatoria limnetica. J. Biol. Chem. 269 (1994) 5705-5711. [PMID: 8119908]
2. Reinartz, M., Tschape, J., Bruser, T., Truper, H.G. and Dahl, C. Sulfide oxidation in the phototrophic sulfur bacterium Chromatium vinosum. Arch. Microbiol. 170 (1998) 59-68. [PMID: 9639604]
3. Nubel, T., Klughammer, C., Huber, R., Hauska, G. and Schutz, M. Sulfide:quinone oxidoreductase in membranes of the hyperthermophilic bacterium Aquifex aeolicus (VF5). Arch. Microbiol. 173 (2000) 233-244. [PMID: 10816041]
4. Brito, J.A., Sousa, F.L., Stelter, M., Bandeiras, T.M., Vonrhein, C., Teixeira, M., Pereira, M.M. and Archer, M. Structural and functional insights into sulfide:quinone oxidoreductase. Biochemistry 48 (2009) 5613-5622. [PMID: 19438211]
5. Cherney, M.M., Zhang, Y., Solomonson, M., Weiner, J.H. and James, M.N. Crystal structure of sulfide:quinone oxidoreductase from Acidithiobacillus ferrooxidans: insights into sulfidotrophic respiration and detoxification. J. Mol. Biol. 398 (2010) 292-305. [PMID: 20303979]
6. Marcia, M., Langer, J.D., Parcej, D., Vogel, V., Peng, G. and Michel, H. Characterizing a monotopic membrane enzyme. Biochemical, enzymatic and crystallization studies on Aquifex aeolicus sulfide:quinone oxidoreductase. Biochim. Biophys. Acta 1798 (2010) 2114-2123. [PMID: 20691146]
*EC 1.8.5.5
Accepted name: thiosulfate reductase (quinone)
Reaction: sulfite + hydrogen sulfide + a quinone = thiosulfate + a quinol
Other name(s): phsABC (gene names)
Systematic name: sulfite,hydrogen sulfide:quinone oxidoreductase
Comments: The enzyme, characterized from the bacterium Salmonella enterica, is similar to EC 1.17.5.3, formate dehydrogenase-N. It contains a molybdopterin-guanine dinucleotide, five [4Fe-4S] clusters and two heme b groups. The reaction occurs in vivo in the direction of thiosulfate disproportionation, which is highly endergonic. It is driven by the proton motive force that occurs across the cytoplasmic membrane.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Kwan, H.S. and Barrett, E.L. Map locations and functions of Salmonella typhimurium men genes. J. Bacteriol. 159 (1984) 1090-1092. [PMID: 6384182]
2. Clark, M.A. and Barrett, E.L. The phs gene and hydrogen sulfide production by Salmonella typhimurium. J. Bacteriol. 169 (1987) 2391-2397. [PMID: 3108233]
3. Alami, N. and Hallenbeck, P.C. Cloning and characterization of a gene cluster, phsBCDEF, necessary for the production of hydrogen sulfide from thiosulfate by Salmonella typhimurium. Gene 156 (1995) 53-57. [PMID: 7737516]
4. Heinzinger, N.K., Fujimoto, S.Y., Clark, M.A., Moreno, M.S. and Barrett, E.L. Sequence analysis of the phs operon in Salmonella typhimurium and the contribution of thiosulfate reduction to anaerobic energy metabolism. J. Bacteriol. 177 (1995) 2813-2820. [PMID: 7751291]
5. Stoffels, L., Krehenbrink, M., Berks, B.C. and Unden, G. Thiosulfate reduction in Salmonella enterica is driven by the proton motive force. J. Bacteriol. 194 (2012) 475-485. [PMID: 22081391]
EC 1.8.5.8
Accepted name: eukaryotic sulfide quinone oxidoreductase
Reaction: hydrogen sulfide + glutathione + a quinone = S-sulfanylglutathione + a quinol
Other name(s): SQR; SQOR; SQRDL (gene name)
Systematic name: sulfide:glutathione,quinone oxidoreductase
Comments: Contains FAD. This eukaryotic enzyme, located at the inner mitochondrial membrane, catalyses the first step in the metabolism of sulfide. While both sulfite and glutathione have been shown to act as sulfane sulfur acceptors in vitro, it is thought that the latter acts as the main acceptor in vivo. The electrons are transferred via FAD and quinones to the electron transfer chain. Unlike the bacterial homolog (EC 1.8.5.4, bacterial sulfide:quinone reductase), which repeats the catalytic cycle without releasing the product, producing a polysulfide, the eukaryotic enzyme transfers the persulfide to an acceptor at the end of each catalytic cycle.
References:
1. Vande Weghe, J.G. and Ow, D.W. A fission yeast gene for mitochondrial sulfide oxidation. J. Biol. Chem. 274 (1999) 13250-13257. [PMID: 10224084]
2. Hildebrandt, T.M. and Grieshaber, M.K. Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria. FEBS J. 275 (2008) 3352-3361. [PMID: 18494801]
3. Jackson, M.R., Melideo, S.L. and Jorns, M.S. Human sulfide:quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite. Biochemistry 51 (2012) 6804-6815. [PMID: 22852582]
4. Libiad, M., Yadav, P.K., Vitvitsky, V., Martinov, M. and Banerjee, R. Organization of the human mitochondrial hydrogen sulfide oxidation pathway. J. Biol. Chem. 289 (2014) 30901-30910. [PMID: 25225291]
EC 1.8.7.3
Accepted name: ferredoxin:CoB-CoM heterodisulfide reductase
Reaction: 2 oxidized ferredoxin [iron-sulfur] cluster + CoB + CoM = 2 reduced ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB + 2 H+
Glossary: CoB = coenzyme B = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate = N-(7-thioheptanoyl)-3-O-phosphothreonine
Other name(s): hdrABC (gene names); hdrA1B1C1 (gene names); hdrA2B2C2 (gene names)
Systematic name: CoB,CoM:ferredoxin oxidoreductase
Comments: HdrABC is an enzyme complex that is found in most methanogens and catalyses the reduction of the CoB-CoM heterodisulfide back to CoB and CoM. HdrA contains a FAD cofactor that acts as the entry point for electrons, which are transferred via HdrC to the HdrB catalytic subunit. One form of the enzyme from Methanosarcina acetivorans (HdrA2B2C2) can also catalyse EC 1.8.98.4, coenzyme F420:CoB-CoM heterodisulfide,ferredoxin reductase. cf. EC 1.8.98.5, H2:CoB-CoM heterodisulfide,ferredoxin reductase, EC 1.8.98.6, formate:CoB-CoM heterodisulfide,ferredoxin reductase, and EC 1.8.98.1, dihydromethanophenazine:CoB-CoM heterodisulfide reductase.
References:
1. Buan, N.R. and Metcalf, W.W. Methanogenesis by Methanosarcina acetivorans involves two structurally and functionally distinct classes of heterodisulfide reductase. Mol. Microbiol. 75 (2010) 843-853. [PMID: 19968794]
2. Yan, Z., Wang, M. and Ferry, J.G. A ferredoxin- and F420H2-dependent, electron-bifurcating, heterodisulfide reductase with homologs in the domains Bacteria and Archaea. mBio 8 (2017) e02285-16. [PMID: 28174314]
*EC 1.8.98.1
Accepted name: dihydromethanophenazine:CoB-CoM heterodisulfide reductase
Reaction: CoB + CoM + methanophenazine = CoM-S-S-CoB + dihydromethanophenazine
For diagram of reaction click here
Glossary: CoB = coenzyme B = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate
Other name(s): hdrDE (gene names); CoB–CoM heterodisulfide reductase (ambiguous); heterodisulfide reductase (ambiguous); coenzyme B:coenzyme M:methanophenazine oxidoreductase
Systematic name: CoB:CoM:methanophenazine oxidoreductase
Comments: This enzyme, found in methanogenic archaea that belong to the Methanosarcinales order, regenerates CoM and CoB after the action of EC 2.8.4.1, coenzyme-B sulfoethylthiotransferase. It is a membrane-bound enzyme that contains (per heterodimeric unit) two distinct b-type hemes and two [4Fe-4S] clusters. cf. EC 1.8.7.3, ferredoxin:CoB-CoM heterodisulfide reductase, EC 1.8.98.5, H2:CoB-CoM heterodisulfide,ferredoxin reductase, EC 1.8.98.6, formate:CoB-CoM heterodisulfide,ferredoxin reductase and EC 1.8.98.4, coenzyme F420:CoB-CoM heterodisulfide,ferredoxin reductase.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Hedderich, R., Berkessel, A. and Thauer, R.K. Purification and properties of heterodisulfide reductase from Methanobacterium thermoautotrophicum (strain Marburg). Eur. J. Biochem. 193 (1990) 255-261. [PMID: 2121478]
2. Abken, H.J., Tietze, M., Brodersen, J., Bäumer, S., Beifuss, U. and Deppenmeier, U. Isolation and characterization of methanophenazine and function of phenazines in membrane-bound electron transport of Methanosarcina mazei gol. J. Bacteriol. 180 (1998) 2027-2032. [PMID: 9555882]
3. Simianu, M., Murakami, E., Brewer, J.M. and Ragsdale, S.W. Purification and properties of the heme- and iron-sulfur-containing heterodisulfide reductase from Methanosarcina thermophila. Biochemistry 37 (1998) 10027-10039. [PMID: 9665708]
4. Murakami, E., Deppenmeier, U. and Ragsdale, S.W. Characterization of the intramolecular electron transfer pathway from 2-hydroxyphenazine to the heterodisulfide reductase from Methanosarcina thermophila. J. Biol. Chem. 276 (2001) 2432-2439. [PMID: 11034998]
EC 1.8.98.4
Accepted name: coenzyme F420:CoB-CoM heterodisulfide,ferredoxin reductase
Reaction: 2 oxidized coenzyme F420 + 2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+ = 2 reduced coenzyme F420 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
Glossary: CoB = coenzyme B = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate = N-(7-thioheptanoyl)-3-O-phosphothreonine
Other name(s): hdrA2B2C2 (gene names)
Systematic name: CoB,CoM,ferredoxin:coenzyme F420 oxidoreductase
Comments: The enzyme, characterized from the archaeon Methanosarcina acetivorans, catalyses the reduction of CoB-CoM heterodisulfide back to CoB and CoM. The enzyme consists of three components, HdrA, HdrB and HdrC, all of which contain [4Fe-4S] clusters. Electrons enter at HdrA, which also contains FAD, and are transferred via HdrC to the catalytic component, HdrB. During methanogenesis from acetate the enzyme catalyses the activity of EC 1.8.7.3, ferredoxin:CoB-CoM heterodisulfide reductase. However, it can also use electron bifurcation to direct electron pairs from reduced coenzyme F420 towards the reduction of both ferredoxin and CoB-CoM heterodisulfide. This activity is proposed to take place during Fe(III)-dependent anaerobic methane oxidation. cf. EC 1.8.98.5, H2:CoB-CoM heterodisulfide,ferredoxin reductase, EC 1.8.98.6, formate:CoB-CoM heterodisulfide,ferredoxin reductase, and EC 1.8.98.1, dihydromethanophenazine:CoB-CoM heterodisulfide reductase.
References:
1. Yan, Z., Wang, M. and Ferry, J.G. A ferredoxin- and F420H2-dependent, electron-bifurcating, heterodisulfide reductase with homologs in the domains Bacteria and Archaea. mBio 8 (2017) e02285-16. [PMID: 28174314]
EC 1.8.98.5
Accepted name: H2:CoB-CoM heterodisulfide,ferredoxin reductase
Reaction: 2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+ = 2 H2 + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
Glossary: CoB = coenzyme B = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate = N-(7-thioheptanoyl)-3-O-phosphothreonine
Systematic name: CoB,CoM,ferredoxin:H2 oxidoreductase
Comments: This enzyme complex is found in H2-oxidizing CO2-reducing methanogenic archaea such as Methanothermobacter thermautotrophicus. It consists of a cytoplasmic complex of HdrABC reductase and MvhAGD hydrogenase. Electron pairs donated by the hydrogenase are transfered via its δ subunit to the HdrA subunit of the reductase, where they are bifurcated, reducing both ferredoxin and CoB-CoM heterodisulfide. The reductase can also form a similar complex with formate dehydrogenase, see EC 1.8.98.6, formate:CoB-CoM heterodisulfide,ferredoxin reductase. cf. EC 1.8.7.3, ferredoxin:CoB-CoM heterodisulfide reductase, EC 1.8.98.4, coenzyme F420:CoB-CoM heterodisulfide,ferredoxin reductase, and EC 1.8.98.1, dihydromethanophenazine:CoB-CoM heterodisulfide reductase.
References:
1. Reeve, J.N., Beckler, G.S., Cram, D.S., Hamilton, P.T., Brown, J.W., Krzycki, J.A., Kolodziej, A.F., Alex, L., Orme-Johnson, W.H. and Walsh, C.T. A hydrogenase-linked gene in Methanobacterium thermoautotrophicum strain δ H encodes a polyferredoxin. Proc. Natl Acad. Sci. USA 86 (1989) 3031-3035. [PMID: 2654933]
2. Hedderich, R., Koch, J., Linder, D. and Thauer, R.K. The heterodisulfide reductase from Methanobacterium thermoautotrophicum contains sequence motifs characteristic of pyridine-nucleotide-dependent thioredoxin reductases. Eur. J. Biochem. 225 (1994) 253-261. [PMID: 7925445]
3. Setzke, E., Hedderich, R., Heiden, S. and Thauer, R.K. H2: heterodisulfide oxidoreductase complex from Methanobacterium thermoautotrophicum. Composition and properties. Eur. J. Biochem. 220 (1994) 139-148. [PMID: 8119281]
4. Stojanowic, A., Mander, G.J., Duin, E.C. and Hedderich, R. Physiological role of the F420-non-reducing hydrogenase (Mvh) from Methanothermobacter marburgensis. Arch. Microbiol. 180 (2003) 194-203. [PMID: 12856108]
5. Kaster, A.K., Moll, J., Parey, K. and Thauer, R.K. Coupling of ferredoxin and heterodisulfide reduction via electron bifurcation in hydrogenotrophic methanogenic archaea. Proc. Natl Acad. Sci. USA 108 (2011) 2981-2986. [PMID: 21262829]
6. Costa, K.C., Lie, T.J., Xia, Q. and Leigh, J.A. VhuD facilitates electron flow from H2 or formate to heterodisulfide reductase in Methanococcus maripaludis. J. Bacteriol. 195 (2013) 5160-5165. [PMID: 24039260]
EC 1.8.98.6
Accepted name: formate:CoB-CoM heterodisulfide,ferredoxin reductase
Reaction: 2 CO2 + 2 reduced ferredoxin [iron-sulfur] cluster + CoB + CoM + 2 H+ = 2 formate + 2 oxidized ferredoxin [iron-sulfur] cluster + CoM-S-S-CoB
Glossary: coenzyme B = CoB = N-(7-mercaptoheptanoyl)threonine 3-O-phosphate = N-(7-thioheptanoyl)-3-O-phosphothreonine
Systematic name: coenzyme B,coenzyme M,ferredoxin:formate oxidoreductase
Comments: The enzyme is found in formate-oxidizing CO2-reducing methanogenic archaea such as Methanothermobacter marburgensis. It consists of a cytoplasmic complex of HdrABC reductase and formate dehydrogenase. Electron pairs donated by formate dehydrogenase are transferred to the HdrA subunit of the reductase, where they are bifurcated, reducing both ferredoxin and CoB-CoM heterodisulfide. cf. EC 1.8.7.3, ferredoxin:CoB-CoM heterodisulfide reductase, EC 1.8.98.4, coenzyme F420:CoB-CoM heterodisulfide,ferredoxin reductase, EC 1.8.98.5, H2:CoB-CoM heterodisulfide,ferredoxin reductase, and EC 1.8.98.1, dihydromethanophenazine:CoB-CoM heterodisulfide reductase.
References:
1. Costa, K.C., Wong, P.M., Wang, T., Lie, T.J., Dodsworth, J.A., Swanson, I., Burn, J.A., Hackett, M. and Leigh, J.A. Protein complexing in a methanogen suggests electron bifurcation and electron delivery from formate to heterodisulfide reductase. Proc. Natl Acad. Sci. USA 107 (2010) 11050-11055. [PMID: 20534465]
2. Costa, K.C., Lie, T.J., Xia, Q. and Leigh, J.A. VhuD facilitates electron flow from H2 or formate to heterodisulfide reductase in Methanococcus maripaludis. J. Bacteriol. 195 (2013) 5160-5165. [PMID: 24039260]
EC 1.13.11.84
Accepted name: crocetin dialdehyde synthase
Reaction: zeaxanthin + 2 O2 = crocetin dialdehyde + 2 3β-hydroxy-β-cyclocitral (overall reaction)
For diagram of reaction click here.
Glossary: crocetin dialdehyde = 8,8'-diapocarotene-8,8'-dial
Other name(s): CCD2; zeaxanthin 7,8-dioxygenase
Systematic name: zeaxanthin:oxygen 7',8'-oxidoreductase (bond-cleaving)
Comments: The enzyme, characterized from the plant Crocus sativus (saffron), acts twice, cleaving 3β-hydroxy-β-cyclocitral off each 3-hydroxy end group. It is part of the zeaxanthin degradation pathway in that plant, leading to the different compounds that impart the color, flavor and aroma of the saffron spice. The enzyme can similarly cleave the 7-8 double bond of other carotenoids with a 3-hydroxy-β-carotenoid end group.
References:
1. Frusciante, S., Diretto, G., Bruno, M., Ferrante, P., Pietrella, M., Prado-Cabrero, A., Rubio-Moraga, A., Beyer, P., Gomez-Gomez, L., Al-Babili, S. and Giuliano, G. Novel carotenoid cleavage dioxygenase catalyzes the first dedicated step in saffron crocin biosynthesis. Proc. Natl. Acad. Sci. USA 111 (2014) 12246-12251. [PMID: 25097262]
2. Ahrazem, O., Rubio-Moraga, A., Berman, J., Capell, T., Christou, P., Zhu, C. and Gomez-Gomez, L. The carotenoid cleavage dioxygenase CCD2 catalysing the synthesis of crocetin in spring crocuses and saffron is a plastidial enzyme. New Phytol. 209 (2016) 650-663. [PMID: 26377696]
3. Ahrazem, O., Diretto, G., Argandona, J., Rubio-Moraga, A., Julve, J.M., Orzaez, D., Granell, A. and Gomez-Gomez, L. Evolutionarily distinct carotenoid cleavage dioxygenases are responsible for crocetin production in Buddleja davidii. J. Exp. Bot. 68 (2017) 4663-4677. [PMID: 28981773]
*EC 1.13.12.7
Accepted name: firefly luciferase
Reaction: D-firefly luciferin + O2 + ATP = firefly oxyluciferin + CO2 + AMP + diphosphate + hν
For diagram of reaction, click here
Glossary: D-firefly luciferin = Photinus-luciferin = (S)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate
Other name(s): Photinus-luciferin 4-monooxygenase (ATP-hydrolysing); luciferase (firefly luciferin); Photinus luciferin 4-monooxygenase (adenosine triphosphate-hydrolyzing); firefly luciferin luciferase; Photinus pyralis luciferase; Photinus-luciferin:oxygen 4-oxidoreductase (decarboxylating, ATP-hydrolysing)
Systematic name: D-firefly luciferin:oxygen 4-oxidoreductase (decarboxylating, ATP-hydrolysing)
Comments: The enzyme, which is found in fireflies (Lampyridae), is responsible for their biolouminescence. The reaction begins with the formation of an acid anhydride between the carboxylic group of D-firefly luciferin and AMP, with the release of diphosphate. An oxygenation follows, with release of the AMP group and formation of a very short-lived peroxide that cyclizes into a dioxetanone structure, which collapses, releasing a CO2 molecule. The spontaneous breakdown of the dioxetanone (rather than the hydrolysis of the adenylate) releases the energy (about 50 kcal/mole) that is necessary to generate the excited state of oxyluciferin. The excited luciferin then emitts a photon, returning to its ground state. The enzyme has a secondary acyl-CoA ligase activity when acting on L-firefly luciferin (see EC 6.2.1.52).
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
PDB,
CAS registry number: 61970-00-1
References:
1. Green, A. A. and McElroy, W. D. Crystalline firefly luciferase. Biochim. Biophys. Acta 20 (1956) 170-176. [PMID: 13315363]
2. White, E.H., McCapra, F., Field, G.F. and McElroy, W.D. The structure and synthesis of firefly luciferin. J. Am. Chem. Soc. 83 (1961) 2402-2403.
3. Hopkins, T.A., Seliger, H.H., White, E.H. and Cass, M.W. The chemiluminescence of firefly luciferin. A model for the bioluminescent reaction and identification of the product excited state. J. Am. Chem. Soc. 89 (1967) 7148-7150. [PMID: 6064360]
4. White, E.H., Rapaport, E., Hopkins, T.A. and Seliger, H.H. Chemi- and bioluminescence of firefly luciferin. J. Am. Chem. Soc. 91 (1969) 2178-2180. [PMID: 5784183]
5. Koo, J.A., Schmidt, S.P. and Schuster, G.B. Bioluminescence of the firefly: key steps in the formation of the electronically excited state for model systems. Proc. Natl Acad. Sci. USA 75 (1978) 30-33. [PMID: 272645]
6. de Wet, J.R., Wood, K.V., Helinski, D.R. and DeLuca, M. Cloning of firefly luciferase cDNA and the expression of active luciferase in Escherichia coli. Proc. Natl Acad. Sci. USA 82 (1985) 7870-7873. [PMID: 3906652]
7. Nakamura, M., Maki, S., Amano, Y., Ohkita, Y., Niwa, K., Hirano, T., Ohmiya, Y. and Niwa, H. Firefly luciferase exhibits bimodal action depending on the luciferin chirality. Biochem. Biophys. Res. Commun. 331 (2005) 471-475. [PMID: 15850783]
8. Sundlov, J.A., Fontaine, D.M., Southworth, T.L., Branchini, B.R. and Gulick, A.M. Crystal structure of firefly luciferase in a second catalytic conformation supports a domain alternation mechanism. Biochemistry 51 (2012) 6493-6495. [PMID: 22852753]
*EC 1.14.11.7
Accepted name: procollagen-proline 3-dioxygenase
Reaction: [procollagen]-L-proline + 2-oxoglutarate + O2 = [procollagen]-trans-3-hydroxy-L-proline + succinate + CO2
For diagram of reaction click here
Other name(s): proline,2-oxoglutarate 3-dioxygenase; prolyl 3-hydroxylase; protocollagen proline 3-hydroxylase; prolyl-4-hydroxyprolyl-glycyl-peptide, 2-oxoglutarate: oxygen oxidoreductase, 3-hydroxylating
Systematic name: [procollagen]-L-proline,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Comments: Requires Fe2+ and ascorbate. The enzyme forms a complex with protein disulfide isomerase, and is located in the endoplasmic reticulum. It modifies proline residues within the procollagen peptide of certain collagen types. The modification is essential for proper collagen triple helix formation.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number: 63551-75-7
References:
1. Risteli, J., Tryggvason, K. and Kivirikko, K.I. Prolyl 3-hydroxylase: partial characterization of the enzyme from rat kidney cortex. Eur. J. Biochem. 73 (1977) 485-492. [PMID: 191255]
2. Risteli, J., Tryggvason, K. and Kivirikko, K.I. A rapid assay for prolyl 3-hydroxylase activity. Anal. Biochem. 84 (1978) 423-431. [PMID: 204218]
3. Vranka, J.A., Sakai, L.Y. and Bachinger, H.P. Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymes. J. Biol. Chem. 279 (2004) 23615-23621. [PMID: 15044469]
4. Tiainen, P., Pasanen, A., Sormunen, R. and Myllyharju, J. Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IV. J. Biol. Chem. 283 (2008) 19432-19439. [PMID: 18487197]
[EC 1.14.13.67 Transferred entry: quinine 3-monooxygenase. Now EC 1.14.14.55, quinine 3-monooxygenase (EC 1.14.13.67 created 2000, deleted 2017)]
[EC 1.14.13.129 Transferred entry: β-carotene 3-hydroxylase. Now EC 1.14.15.24, β-carotene 3-hydroxylase. (EC 1.14.13.129 created 2011, deleted 2017)]
[EC 1.14.13.157 Transferred entry: 1,8-cineole 2-exo-monooxygenase. Now EC 1.14.14.56, 1,8-cineole 2-exo-monooxygenase (EC 1.14.13.157 created 2012, deleted 2017)]
EC 1.14.13.239
Accepted name: carnitine monooxygenase
Reaction: L-carnitine + NAD(P)H + H+ + O2 = (3R)-3-hydroxy-4-oxobutanoate + trimethylamine + NAD(P)+ + H2O
Glossary: (3R)-3-hydroxy-4-oxobutanoate = L-malic semialdehyde
Other name(s): cntAB (gene names); yeaWX (gene names)
Systematic name: L-carnitine,NAD(P)H:oxygen oxidoreductase (trimethylamine-forming)
Comments: The bacterial enzyme is a complex consisting of a reductase and an oxygenase components. The reductase subunit contains a flavin and a plant-type ferredoxin [2Fe-2S] cluster, while the oxygenase subunit is a Rieske-type protein in which a [2Fe-2S] cluster is coordinated by two histidine and two cysteine residues.
References:
1. Ditullio, D., Anderson, D., Chen, C.S. and Sih, C.J. L-carnitine via enzyme-catalyzed oxidative kinetic resolution. Bioorg. Med. Chem. 2 (1994) 415-420. [PMID: 8000862]
2. Zhu, Y., Jameson, E., Crosatti, M., Schafer, H., Rajakumar, K., Bugg, T.D. and Chen, Y. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota. Proc. Natl Acad. Sci. USA 111 (2014) 4268-4273. [PMID: 24591617]
3. Koeth, R.A., Levison, B.S., Culley, M.K., Buffa, J.A., Wang, Z., Gregory, J.C., Org, E., Wu, Y., Li, L., Smith, J.D., Tang, W.H., DiDonato, J.A., Lusis, A.J. and Hazen, S.L. γ-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab 20 (2014) 799-812. [PMID: 25440057]
EC 1.14.14.55
Accepted name: quinine 3-monooxygenase
Reaction: quinine + [reduced NADPH—hemoprotein reductase] + O2 = 3-hydroxyquinine + [oxidized NADPH—hemoprotein reductase] + H2O
Glossary: quinine = a quinoline alkaloid
Other name(s): CYP3A4 (gene name)
Systematic name: quinine,[reduced NADPH–hemoprotein reductase]:oxygen oxidoreductase
Comments: A cytochrome P-450 (heme-thiolate) protein.
References:
1. Relling, M.V., Evans, R., Dass, C., Desiderio, D.M. and Nemec, J. Human cytochrome P450 metabolism of teniposide and etoposide. J. Pharmacol. Exp. Ther. 261 (1992) 491-496. [PMID: 1578365]
2. Zhang, H., Coville, P.F., Walker, R.J., Miners, J.O., Birkett, D.J. and Wanwimolruk, S. Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine. Br. J. Clin. Pharmacol. 43 (1997) 245-252. [PMID: 9088578]
3. Zhao, X.-J., Kawashiro, T. and Ishizaki, T. Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways. Drug Metab. Dispos. 26 (1998) 188-191. [PMID: 9456308]
4. Zhao, X.-J., Yokoyama, H., Chiba, K., Wanwimolruk, S. and Ishizaki, T. Identification of human cytochrome P450 isoforms involved in the 3-hydroxylation of quinine by human liver microsomes and nine recombinant human cytochromes P450. J. Pharmacol. Exp. Ther. 279 (1996) 1327-1334. [PMID: 8968357]
EC 1.14.14.56
Accepted name: 1,8-cineole 2-exo-monooxygenase
Reaction: 1,8-cineole + [reduced NADPH—hemoprotein reductase] + O2 = 2-exo-hydroxy-1,8-cineole + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of reaction click here
Glossary: 1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
Other name(s): CYP3A4
Systematic name: 1,8-cineole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-exo-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein. The mammalian enzyme, expressed in liver microsomes, performs a variety of oxidation reactions of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. cf. EC 1.14.13.97 (taurochenodeoxycholate 6-hydroxylase), EC 1.14.13.67 (quinine 3-monooxygenase) and EC 1.14.13.32 (albendazole monooxygenase).
References:
1. Miyazawa, M., Shindo, M. and Shimada, T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from Eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab. Dispos. 29 (2001) 200-205. [PMID: 11159812]
2. Miyazawa, M. and Shindo, M. Biotransformation of 1,8-cineole by human liver microsomes. Nat. Prod. Lett. 15 (2001) 49-53. [PMID: 11547423]
3. Miyazawa, M., Shindo, M. and Shimada, T. Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica 31 (2001) 713-723. [PMID: 11695850]
EC 1.14.15.24
Accepted name: β-carotene 3-hydroxylase
Reaction: β-carotene + 4 reduced ferredoxin [iron-sulfur] cluster + 2 H+ + 2 O2 = zeaxanthin + 4 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
(overall reaction)
For diagram of reaction click here
Other name(s): β-carotene 3,3'-monooxygenase; CrtZ
Systematic name: β-carotene,reduced ferredoxin [iron-sulfur] cluster:oxygen 3-oxidoreductase
Comments: Requires ferredoxin and Fe(II). Also acts on other carotenoids with a β-end group. In some species canthaxanthin is the preferred substrate.
References:
1. Sun, Z., Gantt, E. and Cunningham, F.X., Jr. Cloning and functional analysis of the β-carotene hydroxylase of Arabidopsis thaliana. J. Biol. Chem. 271 (1996) 24349-24352. [PMID: 8798688]
2. Fraser, P.D., Miura, Y. and Misawa, N. In vitro characterization of astaxanthin biosynthetic enzymes. J. Biol. Chem. 272 (1997) 6128-6135. [PMID: 9045623]
3. Fraser, P.D., Shimada, H. and Misawa, N. Enzymic confirmation of reactions involved in routes to astaxanthin formation, elucidated using a direct substrate in vitro assay. Eur. J. Biochem. 252 (1998) 229-236. [PMID: 9523693]
4. Bouvier, F., Keller, Y., d'Harlingue, A. and Camara, B. Xanthophyll biosynthesis: molecular and functional characterization of carotenoid hydroxylases from pepper fruits (Capsicum annuum L.). Biochim. Biophys. Acta 1391 (1998) 320-328. [PMID: 9555077]
5. Linden, H. Carotenoid hydroxylase from Haematococcus pluvialis: cDNA sequence, regulation and functional complementation. Biochim. Biophys. Acta 1446 (1999) 203-212. [PMID: 10524195]
6. Zhu, C., Yamamura, S., Nishihara, M., Koiwa, H. and Sandmann, G. cDNAs for the synthesis of cyclic carotenoids in petals of Gentiana lutea and their regulation during flower development. Biochim. Biophys. Acta 1625 (2003) 305-308. [PMID: 12591618]
7. Choi, S.K., Matsuda, S., Hoshino, T., Peng, X. and Misawa, N. Characterization of bacterial β-carotene 3,3'-hydroxylases, CrtZ, and P450 in astaxanthin biosynthetic pathway and adonirubin production by gene combination in Escherichia coli. Appl. Microbiol. Biotechnol. 72 (2006) 1238-1246. [PMID: 16614859]
[EC 1.14.99.42 Transferred entry: zeaxanthin 7,8-dioxygenase. Now EC 1.13.11.84, crocetin dialdehyde synthase (EC 1.14.99.42 created 2011, modified 2014, deleted 2017)]
EC 1.14.99.59
Accepted name: tryptamine 4-monooxygenase
Reaction: tryptamine + reduced acceptor + O2 = 4-hydroxytryptamine + acceptor + H2O
For diagram of reaction click here
Glossary: psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate
Other name(s): PsiH
Systematic name: tryptamine,hydrogen-donor:oxygen oxidoreductase (4-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein isolated from the fungus Psilocybe cubensis. Involved in the biosynthesis of the psychoactive compound psilocybin.
References:
1. Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352-12355. [PMID: 28763571]
EC 2.1.1.345
Accepted name: psilocybin synthase
Reaction: 2 S-adenosyl-L-methionine + 4-hydroxytryptamine 4-phosphate = 2 S-adenosyl-L-homocysteine + psilocybin (overall reaction)
For diagram of reaction click here
Glossary: psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate
Other name(s): PsiM
Systematic name: S-adenosyl-L-methionine:4-hydroxytryptamine-4-phosphate N,N-dimethyltransferase
Comments: Isolated from the fungus Psilocybe cubensis. The product, psilocybin, is a psychoactive compound.
References:
1. Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352-12355. [PMID: 28763571]
EC 2.1.3.15
Accepted name: acetyl-CoA carboxytransferase
Reaction: [biotin carboxyl-carrier protein]-N6-carboxybiotinyl-L-lysine + acetyl-CoA = [biotin carboxyl-carrier protein]-N6-biotinyl-L-lysine + malonyl-CoA
Other name(s): accAD (gene names)
Systematic name: [biotin carboxyl-carrier protein]-N6-carboxybiotinyl-L-lysine:acetyl-CoA:carboxytransferase
Comments: The enzyme catalyses the transfer of a carboxyl group carried on a biotinylated biotin carboxyl carrier protein (BCCP) to acetyl-CoA, forming malonyl-CoA. In some organisms this activity is part of a multi-domain polypeptide that includes the carrier protein and EC 6.3.4.14, biotin carboxylase (see EC 6.4.1.2, acetyl-CoA carboxylase). Some enzymes can also carboxylate propanonyl-CoA and butanoyl-CoA (cf. EC 6.4.1.3, propionyl-CoA carboxylase).
References:
1. Bilder, P., Lightle, S., Bainbridge, G., Ohren, J., Finzel, B., Sun, F., Holley, S., Al-Kassim, L., Spessard, C., Melnick, M., Newcomer, M. and Waldrop, G.L. The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme. Biochemistry 45 (2006) 1712-1722. [PMID: 16460018]
2. Chuakrut, S., Arai, H., Ishii, M. and Igarashi, Y. Characterization of a bifunctional archaeal acyl coenzyme A carboxylase. J. Bacteriol. 185 (2003) 938-947. [PMID: 12533469]
*EC 2.3.2.26
Accepted name: HECT-type E3 ubiquitin transferase
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine (overall reaction)
Glossary: HECT protein domain = Homologous to the E6-AP Carboxyl Terminus protein domain
Other name(s): HECT E3 ligase (misleading); ubiquitin transferase HECT-E3; S-ubiquitinyl-[HECT-type E3-ubiquitin transferase]-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming)
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming)
Comments: In the first step the enzyme transfers ubiquitin from the E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) to a cysteine residue in its HECT domain (which is located in the C-terminal region), forming a thioester bond. In a subsequent step the enzyme transfers the ubiquitin to an acceptor protein, resulting in the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the ε-amino group of an L-lysine residue of the acceptor protein. cf. EC 2.3.2.27, RING-type E3 ubiquitin transferase and EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Maspero, E., Mari, S., Valentini, E., Musacchio, A., Fish, A., Pasqualato, S. and Polo, S. Structure of the HECT:ubiquitin complex and its role in ubiquitin chain elongation. EMBO Rep. 12 (2011) 342-349. [PMID: 21399620]
2. Metzger, M.B., Hristova, V.A. and Weissman, A.M. HECT and RING finger families of E3 ubiquitin ligases at a glance. J. Cell Sci. 125 (2012) 531-537. [PMID: 22389392]
*EC 2.3.2.27
Accepted name: RING-type E3 ubiquitin transferase
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
Glossary: RING = Really Interesting New Gene
Other name(s): RING E3 ligase (misleading); ubiquitin transferase RING E3; S-ubiquitinyl-[ubiquitin-conjugating E2 enzyme]-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming, RING-type)
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:[acceptor protein] ubiquitin transferase (isopeptide bond-forming; RING-type)
Comments: RING E3 ubiquitin transferases serve as mediators bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme (EC 2.3.2.23) and an acceptor protein together to enable the direct transfer of ubiquitin through the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the ε-amino group of an L-lysine residue of the acceptor protein. Unlike EC 2.3.2.26, HECT-type E3 ubiquitin transferase, the RING-E3 domain does not form a catalytic thioester intermediate with ubiquitin. Many members of the RING-type E3 ubiquitin transferase family are not able to bind a substrate directly, and form a complex with a cullin scaffold protein and a substrate recognition module (the complexes are named CRL for Cullin-RING-Ligase). In these complexes, the RING-type E3 ubiquitin transferase provides an additional function, mediating the transfer of a NEDD8 protein from a dedicated E2 carrier to the cullin protein (see EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase). cf. EC 2.3.2.31, RBR-type E3 ubiquitin transferase.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Eisele, F. and Wolf, D.H. Degradation of misfolded protein in the cytoplasm is mediated by the ubiquitin ligase Ubr1. FEBS Lett. 582 (2008) 4143-4146. [PMID: 19041308]
2. Metzger, M.B., Hristova, V.A. and Weissman, A.M. HECT and RING finger families of E3 ubiquitin ligases at a glance. J. Cell Sci. 125 (2012) 531-537. [PMID: 22389392]
3. Plechanovova, A., Jaffray, E.G., Tatham, M.H., Naismith, J.H. and Hay, R.T. Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis. Nature 489 (2012) 115-120. [PMID: 22842904]
4. Pruneda, J.N., Littlefield, P.J., Soss, S.E., Nordquist, K.A., Chazin, W.J., Brzovic, P.S. and Klevit, R.E. Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases. Mol. Cell 47 (2012) 933-942. [PMID: 22885007]
5. Metzger, M.B., Pruneda, J.N., Klevit, R.E. and Weissman, A.M. RING -type E3 ligases: master manipulators of E2 ubiquitin-conjugating enzymes and ubiquitination. Biochim. Biophys. Acta 1843 (2014) 47-60. [PMID: 23747565]
EC 2.3.2.31
Accepted name: RBR-type E3 ubiquitin transferase
Reaction: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine (overall reaction)
Glossary: RBR = RING between RING
Systematic name: [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine:acceptor protein ubiquitin transferase (isopeptide bond-forming; RBR-type)
Comments: RBR-type E3 ubiquitin transferases have two RING fingers separated by an internal motif (IBR, for In Between RING). The enzyme interacts with the CRL (Cullin-RING ubiquitin Ligase) complexes formed by certain RING-type E3 ubiquitin transferase (see EC 2.3.2.27), which include a neddylated cullin scaffold protein and a substrate recognition module. The RING1 domain binds an EC 2.3.2.23, E2 ubiquitin-conjugating enzyme, and transfers the ubiquitin that is bound to it to an internal cysteine residue in the RING2 domain, followed by the transfer of the ubiquitin from RING2 to the substrate [4]. Once the substrate has been ubiquitylated by the RBR-type ligase, it can be ubiqutylated further using ubiquitin carried directly on E2 enzymes, in a reaction catalysed by EC 2.3.2.27. Activity of the RBR-type enzyme is dependent on neddylation of the cullin protein in the CRL complex [2,4]. cf. EC 2.3.2.26, HECT-type E3 ubiquitin transferase, EC 2.3.2.27, RING-type E3 ubiquitin transferase, and EC 2.3.2.32, cullin-RING-type E3 NEDD8 transferase.
References:
1. Wenzel, D.M., Lissounov, A., Brzovic, P.S. and Klevit, R.E. UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids. Nature 474 (2011) 105-108. [PMID: 21532592]
2. Kelsall, I.R., Duda, D.M., Olszewski, J.L., Hofmann, K., Knebel, A., Langevin, F., Wood, N., Wightman, M., Schulman, B.A. and Alpi, A.F. TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING ligase complexes. EMBO J. 32 (2013) 2848-2860. [PMID: 24076655]
3. Duda, D.M., Olszewski, J.L., Schuermann, J.P., Kurinov, I., Miller, D.J., Nourse, A., Alpi, A.F. and Schulman, B.A. Structure of HHARI, a RING-IBR-RING ubiquitin ligase: autoinhibition of an Ariadne-family E3 and insights into ligation mechanism. Structure 21 (2013) 1030-1041. [PMID: 23707686]
4. Scott, D.C., Rhee, D.Y., Duda, D.M., Kelsall, I.R., Olszewski, J.L., Paulo, J.A., de Jong, A., Ovaa, H., Alpi, A.F., Harper, J.W. and Schulman, B.A. Two distinct types of E3 ligases work in unison to regulate substrate ubiquitylation. Cell 166 (2016) 1198-1214.e24. [PMID: 27565346]
EC 2.3.2.32
Accepted name: cullin-RING-type E3 NEDD8 transferase
Reaction: S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine + [cullin]-L-lysine = [E2 NEDD8-conjugating enzyme]-L-cysteine + N6-[NEDD8-protein]-yl-[cullin]-L-lysine
Glossary: NEDD = Neural-precursor-cell Expressed Developmentally Down-regulated protein
Other name(s): RBX1 (gene name)
Systematic name: S-[NEDD8-protein]-yl-[E2 NEDD8-conjugating enzyme]-L-cysteine:cullin [NEDD8-protein] transferase (isopeptide bond-forming; RING-type)
Comments: Some RING-type E3 ubiquitin transferase (EC 2.3.2.27) are not able to bind a substrate protein directly. Instead, they form a complex with a cullin scaffold protein and a substrate recognition module, which is named CRL for Cullin-RING-Ligase. The cullin protein needs to be activated by the ubiquitin-like protein NEDD8 in a process known as neddylation. The transfer of NEDD8 from a NEDD8-specific E2 enzyme onto the cullin protein is a secondary function of the RING-type E3 ubiquitin transferase in the CRL complex. The process requires auxiliary factors that belong to the DCN1 (defective in cullin neddylation 1) family.
References:
1. Kim, A.Y., Bommelje, C.C., Lee, B.E., Yonekawa, Y., Choi, L., Morris, L.G., Huang, G., Kaufman, A., Ryan, R.J., Hao, B., Ramanathan, Y. and Singh, B. SCCRO (DCUN1D1) is an essential component of the E3 complex for neddylation. J. Biol. Chem. 283 (2008) 33211-33220. [PMID: 18826954]
2. Kurz, T., Chou, Y.C., Willems, A.R., Meyer-Schaller, N., Hecht, M.L., Tyers, M., Peter, M. and Sicheri, F. Dcn1 functions as a scaffold-type E3 ligase for cullin neddylation. Mol. Cell 29 (2008) 23-35. [PMID: 18206966]
3. Scott, D.C., Monda, J.K., Grace, C.R., Duda, D.M., Kriwacki, R.W., Kurz, T. and Schulman, B.A. A dual E3 mechanism for Rub1 ligation to Cdc53. Mol. Cell 39 (2010) 784-796. [PMID: 20832729]
4. Scott, D.C., Sviderskiy, V.O., Monda, J.K., Lydeard, J.R., Cho, S.E., Harper, J.W. and Schulman, B.A. Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8. Cell 157 (2014) 1671-1684. [PMID: 24949976]
5. Monda, J.K., Scott, D.C., Miller, D.J., Lydeard, J., King, D., Harper, J.W., Bennett, E.J. and Schulman, B.A. Structural conservation of distinctive N-terminal acetylation-dependent interactions across a family of mammalian NEDD8 ligation enzymes. Structure 21 (2013) 42-53. [PMID: 23201271]
EC 2.4.1.348
Accepted name: N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol 3-α-mannosyltransferase
Reaction: GDP-α-D-mannose + N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol = GDP + α-D-mannosyl-(1→3)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
Other name(s): WbdC
Systematic name: GDP-α-D-mannose:N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol 3-α-mannosyltransferase (configuration-retaining)
Comments: The enzyme is involved in the biosynthesis of the linker region of the polymannose O-polysaccharide in the outer leaflet of the membrane of Escherichia coli serotypes O8, O9 and O9a.
References:
1. Greenfield, L.K., Richards, M.R., Li, J., Wakarchuk, W.W., Lowary, T.L. and Whitfield, C. Biosynthesis of the polymannose lipopolysaccharide O-antigens from Escherichia coli serotypes O8 and O9a requires a unique combination of single- and multiple-active site mannosyltransferases. J. Biol. Chem. 287 (2012) 35078-35091. [PMID: 22875852]
EC 2.4.1.349
Accepted name: mannosyl-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol 3-α-mannosyltransferase
Reaction: 2 GDP-α-D-mannose + α-D-mannosyl-(1→3)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol = 2 GDP + α-D-mannosyl-(1→3)-α-D-mannosyl-(1→3)-α-D-mannosyl-(1→3)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol
Other name(s): WbdB
Systematic name: GDP-α-D-mannose:α-D-mannosyl-(1→3)-N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol 3-α-mannosyltransferase (configuration-retaining)
Comments: The enzyme is involved in the biosynthesis of the linker region of the polymannose O-polysaccharide in the outer leaflet of the membrane of Escherichia coli serotypes O8, O9 and O9a. It has no activity with N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol (cf. EC 2.4.1.348, N-acetyl-α-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol 3-α-mannosyltransferase).
References:
1. Greenfield, L.K., Richards, M.R., Li, J., Wakarchuk, W.W., Lowary, T.L. and Whitfield, C. Biosynthesis of the polymannose lipopolysaccharide O-antigens from Escherichia coli serotypes O8 and O9a requires a unique combination of single- and multiple-active site mannosyltransferases. J. Biol. Chem. 287 (2012) 35078-35091. [PMID: 22875852]
EC 2.4.1.350
Accepted name: mogroside IE synthase
Reaction: UDP-α-D-glucose + mogrol = mogroside IE + UDP
Glossary: mogrol = (23R)-cucurbit-5-ene-3β,11α,23,25-tetraol
Other name(s): UGT74AC1; mogrol C-3 hydroxyl glycosyltransferase
Systematic name: UDP-α-D-glucose:mogrol 3-O-glucosyltransferase
Comments: Isolated from the plant Siraitia grosvenorii (monk fruit).
References:
1. Dai, L., Liu, C., Zhu, Y., Zhang, J., Men, Y., Zeng, Y. and Sun, Y. Functional characterization of cucurbitadienol synthase and triterpene glycosyltransferase involved in biosynthesis of mogrosides from Siraitia grosvenorii. Plant Cell Physiol 56 (2015) 1172-1182. [PMID: 25759326]
EC 2.5.1.142
Accepted name: nerylneryl diphosphate synthase
Reaction: dimethylallyl diphosphate + 3 isopentenyl diphosphate = 3 diphosphate + nerylneryl diphosphate
For diagram of reaction click here
Glossary: nerylneryl diphosphate = all-cis-tetraprenyl diphosphate
Other name(s): CPT2
Systematic name: dimethylallyl-diphosphate:isopentenyl-diphosphate cistransferase (adding 3 isopentenyl units)
Comments: Isolated from the plant Solanum lycopersicum (tomato).
References:
1. Akhtar, T.A., Matsuba, Y., Schauvinhold, I., Yu, G., Lees, H.A., Klein, S.E. and Pichersky, E. The tomato cis-prenyltransferase gene family. Plant J. 73 (2013) 640-652. [PMID: 23134568]
2. Matsuba, Y., Zi, J., Jones, A.D., Peters, R.J. and Pichersky, E. Biosynthesis of the diterpenoid lycosantalonol via nerylneryl diphosphate in Solanum lycopersicum. PLoS One 10 (2015) e0119302. [PMID: 25786135]
*EC 2.7.1.181
Accepted name: polymannosyl GlcNAc-diphospho-ditrans,octacis-undecaprenol kinase
Reaction: ATP + α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol = ADP + 3-O-phospho-α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol
Other name(s): WbdD; ATP:α-D-Man-(1→2)-α-D-Man-(1→2)-α-D-Man-(1→3)-α-D-Man-(1→3)-[α-D-Man-(1→2)-α-D-Man-(1→2)-α-D-Man-(1→3)-α-D-Man-(1→3)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol 3-phosphotransferase
Systematic name: ATP:α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol 3-phosphotransferase
Comments: The enzyme is involved in the biosynthesis of the polymannose O-polysaccharide in the outer leaflet of the membrane of Escherichia coli serotype O9a. O-Polysaccharide structures vary extensively because of differences in the number and type of sugars in the repeat unit. The dual kinase/methylase WbdD also catalyses the methylation of 3-phospho-α-D-Man-(1→2)-α-D-Man-(1→2)-[α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→2)-α-D-Man-(1→2)]n-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-Man-(1→3)-α-D-GlcNAc-diphospho-ditrans,octacis-undecaprenol (cf. EC 2.1.1.294, 3-O-phospho-polymannosyl GlcNAc-diphospho-ditrans,octacis-undecaprenol 3-phospho-methyltransferase)
Links to other databases:
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CAS registry number:
References:
1. Clarke, B.R., Cuthbertson, L. and Whitfield, C. Nonreducing terminal modifications determine the chain length of polymannose O antigens of Escherichia coli and couple chain termination to polymer export via an ATP-binding cassette transporter. J. Biol. Chem. 279 (2004) 35709-35718. [PMID: 15184370]
2. Clarke, B.R., Greenfield, L.K., Bouwman, C. and Whitfield, C. Coordination of polymerization, chain termination, and export in assembly of the Escherichia coli lipopolysaccharide O9a antigen in an ATP-binding cassette transporter-dependent pathway. J. Biol. Chem. 284 (2009) 30662-30672. [PMID: 19734145]
3. Clarke, B.R., Richards, M.R., Greenfield, L.K., Hou, D., Lowary, T.L. and Whitfield, C. In vitro reconstruction of the chain termination reaction in biosynthesis of the Escherichia coli O9a O-polysaccharide: the chain-length regulator, WbdD, catalyzes the addition of methyl phosphate to the non-reducing terminus of the growing glycan. J. Biol. Chem. 286 (2011) 41391-41401. [PMID: 21990359]
4. Liston, S.D., Clarke, B.R., Greenfield, L.K., Richards, M.R., Lowary, T.L. and Whitfield, C. Domain interactions control complex formation and polymerase specificity in the biosynthesis of the Escherichia coli O9a antigen. J. Biol. Chem. 290 (2015) 1075-1085. [PMID: 25422321]
EC 2.7.1.222
Accepted name: 4-hydroxytryptamine kinase
Reaction: ATP + 4-hydroxytryptamine = ADP + 4-hydoxytryptamine 4-phosphate
For diagram of reaction click here
Glossary: psilocybin = 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl phosphate
Other name(s): PsiK
Systematic name: ATP:4-hydroxytryptamine 4-phosphotransferase
Comments: Also acts on 4-hydroxy-L-tryptophan in vitro. Isolated from the fungus Psilocybe cubensis. Involved in the biosynthesis of the psychoactive compound psilocybin.
References:
1. Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352-12355.
EC 2.7.3.13
Accepted name: glutamine kinase
Reaction: ATP + L-glutamine + H2O = AMP + phosphate + N5-phospho-L-glutamine
Systematic name: ATP:L-glutamine N5-phosphotransferase
Comments: The enzyme, characterized from the bacterium Campylobacter jejuni, is involved in formation of a unique O-methyl phosphoramidate modification on specific sugar residues within the bacterium's capsular polysaccharides.
References:
1. Taylor, Z.W., Brown, H.A., Narindoshvili, T., Wenzel, C.Q., Szymanski, C.M., Holden, H.M. and Raushel, F.M. Discovery of a glutamine kinase required for the biosynthesis of the O-methyl phosphoramidate modifications found in the capsular polysaccharides of Campylobacter jejuni. J. Am. Chem. Soc. 139 (2017) 9463-9466. [PMID: 28650156]
[EC 2.7.7.94 Transferred entry: 4-hydroxyphenylalkanoate adenylyltransferase. Now EC 6.2.1.51, 4-hydroxyphenylalkanoate adenylyltransferase FadD29 (EC 2.7.7.94 created 2016, deleted 2017)]
EC 3.2.1.206
Accepted name: oleuropein β-glucosidase
Reaction: oleuropein + H2O = oleuropein aglycone + D-glucopyranose
Glossary: oleuropein aglycone = methyl (2S,3E,4S)-4-{2-[2-(3,4-dihydroxyphenyl)ethoxy]-2-oxoethyl}-3-ethylidene-2-hydroxy-3,4-dihydro-2H-pyran-5-carboxylate
Other name(s): OeGLU (gene name)
Systematic name: oleuropein 2-β-D-glucohydrolase
Comments: Oleuropein is a glycosylated secoiridoid exclusively biosynthesized by members of the Oleaceae plant family where it is part of a defence system againt herbivores. The enzyme also hydrolyses ligstroside and demethyloleuropein.
References:
1. Ciafardini, G., Marsilio, V., Lanza, B. and Pozzi, N. Hydrolysis of oleuropein by Lactobacillus plantarum strains associated with olive fermentation. Appl. Environ. Microbiol. 60 (1994) 4142-4147. [PMID: 16349442]
2. Romero-Segura, C., Sanz, C. and Perez, A.G. Purification and characterization of an olive fruit β-glucosidase involved in the biosynthesis of virgin olive oil phenolics. J. Agric. Food Chem. 57 (2009) 7983-7988. [PMID: 19689134]
3. Gutierrez-Rosales, F., Romero, M.P., Casanovas, M., Motilva, M.J. and Minguez-Mosquera, M.I. β-Glucosidase involvement in the formation and transformation of oleuropein during the growth and development of olive fruits (Olea europaea L. cv. Arbequina) grown under different farming practices. J. Agric. Food Chem. 60 (2012) 4348-4358. [PMID: 22475562]
4. Koudounas, K., Banilas, G., Michaelidis, C., Demoliou, C., Rigas, S. and Hatzopoulos, P. A defence-related Olea europaea β-glucosidase hydrolyses and activates oleuropein into a potent protein cross-linking agent. J. Exp. Bot. 66 (2015) 2093-2106. [PMID: 25697790]
5. Koudounas, K., Thomopoulou, M., Michaelidis, C., Zevgiti, E., Papakostas, G., Tserou, P., Daras, G. and Hatzopoulos, P. The C-domain of oleuropein β-glucosidase assists in protein folding and sequesters the enzyme in nucleus. Plant Physiol. 174 (2017) 1371-1383. [PMID: 28483880]
*EC 3.3.2.9
Accepted name: microsomal epoxide hydrolase
Reaction: (1) cis-stilbene oxide + H2O = (1R,2R)-1,2-diphenylethane-1,2-diol
Glossary: oxirane = ethylene oxide = a 3-membered oxygen-containing ring
Other name(s): microsomal oxirane/oxetane hydrolase; epoxide hydratase (ambiguous); microsomal epoxide hydratase (ambiguous); epoxide hydrase; microsomal epoxide hydrase; arene-oxide hydratase (ambiguous); benzo[a]pyrene-4,5-oxide hydratase; benzo(a)pyrene-4,5-epoxide hydratase; aryl epoxide hydrase (ambiguous); cis-epoxide hydrolase; mEH; EPHX1 (gene name)
Systematic name: cis-stilbene-oxide hydrolase
Comments: This is a key hepatic enzyme that catalyses the hydrolytic ring opening of oxiranes (epoxides) and oxetanes to give the corresponding diols. The enzyme is involved in the metabolism of numerous substrates including the stereoselective hydrolytic ring opening of 7-oxabicyclo[4.1.0]hepta-2,4-dienes (arene oxides) to the corresponding trans-dihydrodiols. The reaction proceeds via a triad mechanism and involves the formation of an hydroxyalkyl-enzyme intermediate. Five epoxide-hydrolase enzymes have been identified in vertebrates to date: EC 3.3.2.6 (leukotriene-A4 hydrolase), EC 3.3.2.7 (hepoxilin-epoxide hydrolase), EC 3.3.2.9 (microsomal epoxide hydrolase), EC 3.3.2.10 (soluble epoxide hydrolase) and EC 3.3.2.11 (cholesterol-5,6-oxide hydrolase).
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Oesch, F. and Daly, J. Solubilization, purification, and properties of a hepatic epoxide hydrase. Biochim. Biophys. Acta 227 (1971) 692-697. [PMID: 4998715]
2. Jakoby, W.B. and Fjellstedt, T.A. Epoxidases. In: Boyer, P.D. (Ed.), The Enzymes, 3rd edn, vol. 7, Academic Press, New York, 1972, pp. 199-212.
3. Oesch, F. Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds. Xenobiotica 3 (1973) 305-340. [PMID: 4584115]
4. Oesch, F. Purification and specificity of a human microsomal epoxide hydratase. Biochem. J. 139 (1974) 77-88. [PMID: 4463951]
5. Lu, A.Y., Ryan, D., Jerina, D.M., Daly, J.W. and Levin, W. Liver microsomal expoxide hydrase. Solubilization, purification, and
characterization. J. Biol. Chem. 250 (1975) 8283-8288. [PMID: 240858]
6. Bellucci, G., Chiappe, C. and Ingrosso, G. Kinetics and stereochemistry of the microsomal epoxide hydrolase-catalyzed hydrolysis of cis-stilbene oxides. Chirality 6 (1994) 577-582. [PMID: 7986671]
7. Fretland, A.J. and Omiecinski, C.J. Epoxide hydrolases: biochemistry and molecular biology. Chem. Biol. Interact. 129 (2000) 41-59. [PMID: 11154734]
8. Morisseau, C. and Hammock, B.D. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 311-333. [PMID: 15822179]
9. Newman, J.W., Morisseau, C. and Hammock, B.D. Epoxide hydrolases: their roles and interactions with lipid metabolism. Prog. Lipid Res. 44 (2005) 1-51. [PMID: 15748653]
10. Toselli, F., Fredenwall, M., Svensson, P., Li, X.Q., Johansson, A., Weidolf, L. and Hayes, M.A. Oxetane substrates of human microsomal epoxide hydrolase. Drug Metab. Dispos. 45 (2017) 966-973. [PMID: 28600384]
EC 4.1.1.105
Accepted name: L-tryptophan decarboxylase
Reaction: L-typtophan = tryptamine + CO2
For diagram of reaction click here
Other name(s): psiD (gene name); TDC (gene name)
Systematic name: L-tryptophan carboxy-lyase
Comments: The enzyme has been characterized from bacteria, plants, and fungi. Unlike EC 4.1.1.28, aromatic-L-amino-acid decarboxylase, this enzyme is specific for L-typtophan.
References:
1. Noe, W., Mollenschott, C. and Berlin, J. Tryptophan decarboxylase from Catharanthus roseus cell suspension cultures: purification, molecular and kinetic data of the homogenous protein. Plant Mol. Biol. 3 (1984) 281-288. [PMID: 24310513]
2. Buki, K.G., Vinh, D.Q. and Horvath, I. Partial purification and some properties of tryptophan decarboxylase from a Bacillus strain. Acta Microbiol Hung 32 (1985) 65-73. [PMID: 4036551]
3. Nakazawa, H., Kumagai, H. and Yamada, H. Constitutive aromatic L-amino acid decarboxylase from Micrococcus percitreus. Biochem. Biophys. Res. Commun. 61 (1974) 75-82. [PMID: 4441405]
4. Lopez-Meyer, M. and Nessler, C.L. Tryptophan decarboxylase is encoded by two autonomously regulated genes in Camptotheca acuminata which are differentially expressed during development and stress. Plant J. 11 (1997) 1167-1175. [PMID: 9225462]
5. Fricke, J., Blei, F. and Hoffmeister, D. Enzymatic synthesis of psilocybin. Angew. Chem. Int. Ed. Engl. 56 (2017) 12352-12355. [PMID: 28763571]
EC 4.1.1.106
Accepted name: fatty acid photodecarboxylase
Reaction: a long-chain fatty acid + hν = a long-chain alkane + CO2
Other name(s): FAP (gene name)
Systematic name: fatty acid carboxy-lyase (light-dependent, alkane-forming)
Comments: This algal enzyme, characterized from the green algae Chlorella variabilis and Chlamydomonas reinhardtii, is dependent on blue light, which photooxidizes its FAD cofactor. The enzyme acts on fatty acids in the range of C12 to C22, with a higher efficiency for C16 to C17 chains, and forms an alkane product that is one carbon shorter than the substrate. The enzyme can also act on unsaturated fatty acids, forming the respective alkenes, but does not generate a new double bond.
References:
1. Sorigue, D., Legeret, B., Cuine, S., Blangy, S., Moulin, S., Billon, E., Richaud, P., Brugiere, S., Coute, Y., Nurizzo, D., Muller, P., Brettel, K., Pignol, D., Arnoux, P., Li-Beisson, Y., Peltier, G. and Beisson, F. An algal photoenzyme converts fatty acids to hydrocarbons. Science 357 (2017) 903-907. [PMID: 28860382]
EC 4.1.1.107
Accepted name: 3,4-dihydroxyphenylacetaldehyde synthase
Reaction: L-dopa + O2 + H2O = 3,4-dihydroxyphenylacetaldehyde + CO2 + NH3 + H2O2
For diagram of reaction click here
Glossary: L-dopa = 3,4-dihydroxyphenylalanine
Other name(s): DHPAA synthase
Systematic name: L-dopa carboxy-lyase (oxidative-deaminating)
Comments: A pyridoxal 5'-phosphate protein. The enzyme, isolated from the mosquito Aedes aegypti, catalyses the production of 3,4-dihydroxylphenylacetaldehyde directly from L-dopa. Dopamine is not formed as an intermediate (cf. EC 4.1.1.28, aromatic-L-amino-acid decarboxylase). The enzyme is specific for L-dopa and does not react with other aromatic amino acids with the exception of a low activity with α-methyl-L-dopa.
References:
1. Vavricka, C., Han, Q., Huang, Y., Erickson, S.M., Harich, K., Christensen, B.M. and Li, J. From L-dopa to dihydroxyphenylacetaldehyde: a toxic biochemical pathway plays a vital physiological function in insects. PLoS One 6 (2011) e16124. [PMID: 21283636]
EC 4.1.1.108
Accepted name: 4-hydroxyphenylacetaldehyde synthase
Reaction: L-tyrosine + O2 + H2O = (4-hydroxyphenyl)acetaldehyde + CO2 + NH3 + H2O2
For diagram of reaction click here
Other name(s): TYRDC-2 (gene name)
Systematic name: L-tyrosine carboxy-lyase (oxidative-deaminating)
Comments: A pyridoxal 5'-phosphate protein. The enzyme, isolated from the the plant Petroselinum crispum (parsley), catalyses the production of 4-hydroxyphenylacetaldehyde directly from L-tyrosine. Tyramine is not formed as an intermediate. The enzyme has a low activity with L-dopa (cf. EC 4.1.1.107, 3,4-dihydroxyphenylacetaldehyde synthase).
References:
1. Torrens-Spence, M.P., Gillaspy, G., Zhao, B., Harich, K., White, R.H. and Li, J. Biochemical evaluation of a parsley tyrosine decarboxylase results in a novel 4-hydroxyphenylacetaldehyde synthase enzyme. Biochem. Biophys. Res. Commun. 418 (2012) 211-216. [PMID: 22266321]
2. Torrens-Spence, M.P., Liu, P., Ding, H., Harich, K., Gillaspy, G. and Li, J. Biochemical evaluation of the decarboxylation and decarboxylation-deamination activities of plant aromatic amino acid decarboxylases. J. Biol. Chem. 288 (2013) 2376-2387. [PMID: 23204519]
EC 4.1.1.109
Accepted name: phenylacetaldehyde synthase
Reaction: L-phenylalanine + O2 + H2O = phenylacetaldehyde + CO2 + NH3 + H2O2
For diagram of reaction click here
Other name(s): PAAS (gene name)
Systematic name: L-phenylalanine carboxy-lyase (oxidative-deaminating)
Comments: A pyridoxal 5'-phosphate protein. The enzyme, isolated from the the plants Petunia hybrida and a Rosa hybrid, catalyses the production of phenylacetaldehyde directly from L-phenylalanine. The enzyme is specific for L-phenylalanine and does not accept other aromatic amino acids as substrates.
References:
1. Kaminaga, Y., Schnepp, J., Peel, G., Kish, C.M., Ben-Nissan, G., Weiss, D., Orlova, I., Lavie, O., Rhodes, D., Wood, K., Porterfield, D.M., Cooper, A.J., Schloss, J.V., Pichersky, E., Vainstein, A. and Dudareva, N. Plant phenylacetaldehyde synthase is a bifunctional homotetrameric enzyme that catalyzes phenylalanine decarboxylation and oxidation. J. Biol. Chem. 281 (2006) 23357-23366. [PMID: 16766535]
EC 4.1.99.23
Accepted name: 5-hydroxybenzimidazole synthase
Reaction: 5-amino-1-(5-phospho-β-D-ribosyl)imidazole + S-adenosyl-L-methionine + reduced acceptor = 5-hydroxybenzimidazole + 5'-deoxyadenosine + L-methionine + formate + NH3 + phosphate + oxidized acceptor
For diagram of reaction click here
Other name(s): bzaF (gene name); HBI synthase
Systematic name: 5-amino-1-(5-phospho-β-D-ribosyl)imidazole formate-lyase (decarboxylating, 4-amino-2-methyl-5-(phosphooxymethyl)pyrimidine-forming)
Comments: The enzyme, purified from bacteria, is part of the anaerobic pathway for cobalamin biosynthesis. It binds a [4Fe-4S] cluster that is coordinated by 3 cysteines and an exchangeable S-adenosyl-L-methionine molecule. The first stage of catalysis is reduction of the S-adenosyl-L-methionine to produce L-methionine and a 5'-deoxyadenosin-5'-yl radical that is crucial for the conversion of the substrate.
References:
1. Mehta, A.P., Abdelwahed, S.H., Fenwick, M.K., Hazra, A.B., Taga, M.E., Zhang, Y., Ealick, S.E. and Begley, T.P. Anaerobic 5-hydroxybenzimidazole formation from aminoimidazole ribotide: an unanticipated intersection of thiamin and vitamin B12 biosynthesis. J. Am. Chem. Soc. 137 (2015) 10444-10447. [PMID: 26237670]
2. Hazra, A.B., Han, A.W., Mehta, A.P., Mok, K.C., Osadchiy, V., Begley, T.P. and Taga, M.E. Anaerobic biosynthesis of the lower ligand of vitamin B12. Proc. Natl Acad. Sci. USA 112 (2015) 10792-10797. [PMID: 26246619]
*EC 4.2.3.141
Accepted name: sclareol synthase
Reaction: (13E)-8α-hydroxylabd-13-en-15-yl diphosphate + H2O = sclareol + diphosphate
For diagram of reaction click here
Glossary: sclareol = (13R)-labd-14-ene-8α,13-diol
Other name(s): SS
Systematic name: (13E)-8α-hydroxylabd-13-en-15-yl-diphosphate-lyase (sclareol forming)
Comments: Isolated from the plant Salvia sclarea (clary sage). Originally thought to be synthesized in one step from geranylgeranyl diphosphate it is now known to require two enzymes, EC 4.2.1.133, copal-8-ol diphosphate synthase and EC 4.2.3.141, sclareol synthase. Sclareol is used in perfumery.
Links to other databases:
BRENDA,
EXPASY,
KEGG,
MetaCyc,
CAS registry number:
References:
1. Caniard, A., Zerbe, P., Legrand, S., Cohade, A., Valot, N., Magnard, J.L., Bohlmann, J. and Legendre, L. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture. BMC Plant Biol. 12 (2012) 119. [PMID: 22834731]
EC 4.2.3.195
Accepted name: rhizathalene A synthase
Reaction: geranylgeranyl diphosphate = rhizathalene A + diphosphate
For diagram of reaction click here and mechanism click here
Other name(s): TPS08 (gene name)
Systematic name: geranygeranyl-diphosphate diphosphate-lyase (rhizathalene A-forming)
Comments: The enzyme was identified in the roots of the plant Arabidopsis thaliana (thale cress). The product is a semivolatile diterpene that acts as a local antifeedant in belowground direct defense against root-feeding insects.
References:
1. Vaughan, M.M., Wang, Q., Webster, F.X., Kiemle, D., Hong, Y.J., Tantillo, D.J., Coates, R.M., Wray, A.T., Askew, W., O'Donnell, C., Tokuhisa, J.G. and Tholl, D. Formation of the unusual semivolatile diterpene rhizathalene by the Arabidopsis class I terpene synthase TPS08 in the root stele is involved in defense against belowground herbivory. Plant Cell 25 (2013) 1108-1125. [PMID: 23512856]
EC 4.99.1.12
Accepted name: pyridinium-3,5-bisthiocarboxylic acid mononucleotide nickel chelatase
Reaction: Ni(II)-pyridinium-3,5-bisthiocarboxylate mononucleotide = pyridinium-3,5-bisthiocarboxylate mononucleotide + Ni2+
Other name(s): LarC; P2TMN nickel chelatase
Systematic name: Ni(II)-pyridinium-3,5-bisthiocarboxylate mononucleotide nickel-lyase (pyridinium-3,5-bisthiocarboxylate-mononucleotide forming)
Comments: This enzyme, found in Lactobacillus plantarum, is involved in the biosynthesis of a nickel-pincer cofactor. It catalyses the insertion of Ni2+ into the cofactor forming a covalent bond between a carbon atom and the nickel atom.
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]
EC 6.2.1.51
Accepted name: 4-hydroxyphenylalkanoate adenylyltransferase FadD29
Reaction: (1) ATP + 17-(4-hydroxyphenyl)heptadecanoate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + 17-(4-hydroxyphenyl)heptadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
Other name(s): fadD29 (gene name); 4-hydroxyphenylalkanoate adenylase
Systematic name: 4-hydroxyphenylalkanoate:holo-[(phenol)carboxyphthiodiolenone synthase] ligase
Comments: The mycobacterial enzyme participates in the biosynthesis of phenolphthiocerols. Following the substrate’s activation by adenylation, it is transferred to an acyl-carrier protein domain within the enzyme, from which it is transferred to the phenolphthiocerol/phthiocerol polyketide synthase.
References:
1. Simeone, R., Leger, M., Constant, P., Malaga, W., Marrakchi, H., Daffe, M., Guilhot, C. and Chalut, C. Delineation of the roles of FadD22, FadD26 and FadD29 in the biosynthesis of phthiocerol dimycocerosates and related compounds in Mycobacterium tuberculosis. FEBS J. 277 (2010) 2715-2725. [PMID: 20553505]
2. Vergnolle, O., Chavadi, S.S., Edupuganti, U.R., Mohandas, P., Chan, C., Zeng, J., Kopylov, M., Angelo, N.G., Warren, J.D., Soll, C.E. and Quadri, L.E. Biosynthesis of cell envelope-associated phenolic glycolipids in Mycobacterium marinum. J. Bacteriol. 197 (2015) 1040-1050. [PMID: 25561717]
EC 6.2.1.52
Accepted name: L-firefly luciferin—CoA ligase
Reaction: ATP + L-firefly luciferin + CoA = AMP + diphosphate + L-firefly luciferyl-CoA
Glossary: L-firefly luciferin = (R)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate
Other name(s): LUC
Systematic name: (R)-4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazole-4-carboxylate:CoA ligase (AMP-forming)
Comments: This is an alternative activity of the firefly luciferase (EC 1.13.12.7), which the enzyme exhibits under normal conditions only when acting on the L-enantiomer of its substrate. The D-isomer can act as a substrate for the CoA–ligase activity in vitro only under low oxygen conditions that are not found in vivo. The activation of L-firefly luciferin to a CoA ester is a step in a recycling pathway that results in its epimerization to the D enantiomer, which is the only substrate whose oxygenation results in light emission.
References:
1. Fraga, H., Esteves da Silva, J.C. and Fontes, R. Identification of luciferyl adenylate and luciferyl coenzyme a synthesized by firefly luciferase. Chembiochem 5 (2004) 110-115. [PMID: 14695520]
2. Nakamura, M., Maki, S., Amano, Y., Ohkita, Y., Niwa, K., Hirano, T., Ohmiya, Y. and Niwa, H. Firefly luciferase exhibits bimodal action depending on the luciferin chirality. Biochem. Biophys. Res. Commun. 331 (2005) 471-475. [PMID: 15850783]
3. Viviani, V.R., Scorsato, V., Prado, R.A., Pereira, J.G., Niwa, K., Ohmiya, Y. and Barbosa, J.A. The origin of luciferase activity in Zophobas mealworm AMP/CoA-ligase (protoluciferase): luciferin stereoselectivity as a switch for the oxygenase activity. Photochem Photobiol Sci 9 (2010) 1111-1119. [PMID: 20526507]
4. Maeda, J., Kato, D.I., Okuda, M., Takeo, M., Negoro, S., Arima, K., Ito, Y. and Niwa, K. Biosynthesis-inspired deracemizative production of D-luciferin by combining luciferase and thioesterase. Biochim. Biophys. Acta 1861 (2017) 2112-2118. [PMID: 28454735]
CoM = coenzyme M = 2-mercaptoethanesulfonate
CoM-S-S-CoB = CoB-CoM heterodisulfide = N-{7-[(2-sulfoethyl)dithio]heptanoyl}-O3-phospho-L-threonine
CoB = coenzyme M = 2-mercaptoethanesulfonate
methanophenazine = 2-{[(6E,10E,14E)-3,7,11,15,19-pentamethylicosa-6,10,14,18-tetraen-1-yl]oxy}phenazine
CoM-S-S-CoB = CoB-CoM heterodisulfide = N-{7-[(2-sulfoethyl)dithio]heptanoyl}-O3-phospho-L-threonine
CoM = coenzyme M = 2-mercaptoethanesulfonate
CoM-S-S-CoB = CoB-CoM heterodisulfide = N-{7-[(2-sulfoethyl)dithio]heptanoyl}-O3-phospho-L-threonine
CoM = coenzyme M = 2-mercaptoethanesulfonate
CoM-S-S-CoB = CoB-CoM heterodisulfide = N-{7-[(2-sulfoethyl)dithio]heptanoyl}-O3-phospho-L-threonine
coenzyme M = CoM = 2-mercaptoethanesulfonate
CoM-S-S-CoB = CoB-CoM heterodisulfide = N-{7-[(2-sulfoethyl)dithio]heptanoyl}-O3-phospho-L-threonine
(1a) zeaxanthin + O2 = 3β-hydroxy-8'-apo-β-carotenal + 3β-hydroxy-β-cyclocitral
(1b) 3β-hydroxy-8'-apo-β-carotenal + O2 = crocetin dialdehyde + 3β-hydroxy-β-cyclocitral
zeaxanthin = (3R,3'R)-β,β-carotene-3,3'-diol
3β-hydroxy-β-cyclocitral = (4R)-4-hydroxy-2,6,6-trimethylcyclohex-1-en-1-carboxaldehyde
firefly oxyluciferin = 4,5-dihydro-2-(6-hydroxy-1,3-benzothiazol-2-yl)thiazol-4-one
2-exo-hydroxy-1,8-cineole = (1R,4S,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol
(1a) β-carotene + 2 reduced ferredoxin [iron-sulfur] cluster + H+ + O2 = β-cryptoxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1b) β-cryptoxanthin + 2 reduced ferredoxin [iron-sulfur] cluster + H+ + O2 = zeaxanthin + 2 oxidized ferredoxin [iron-sulfur] cluster + H2O
(1a) S-adenosyl-L-methionine + 4-hydroxytryptamine 4-phosphate = S-adenosyl-L-homocysteine + 4-hydroxy-N-methyltryptamine 4-phosphate
(1b) S-adenosyl-L-methionine + 4-hydroxy-N-methyltryptamine 4-phosphate = S-adenosyl-L-homocysteine + psilocybin
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [HECT-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [HECT-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [HECT-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [HECT-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
(1a) [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [RBR-type E3 ubiquitin transferase]-L-cysteine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine
(1b) [RBR-type E3 ubiquitin transferase]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [RBR-type E3 ubiquitin transferase]-L-cysteine + [acceptor protein]-N6-ubiquitinyl-L-lysine
RING = Really Interesting New Gene
oleuropein = methyl (2R,3E,4S)-4-{2-[2-(3,4-dihydroxyphenyl)ethoxy]-2-oxoethyl}-3-ethylidene-2-(β-D-glucopyranosyloxy)-3,4-dihydro-2H-pyran-5-carboxylate
ligstroside = methyl (2S,3E,4S)-3-ethylidene-2-(β-D-glucopyranosyloxy)-4-{2-[2-(4-hydroxyphenyl)ethoxy]-2-oxoethyl}-3,4-dihydro-2H-pyran-5-carboxylate
(2) 1-(4-methoxyphenyl)-N-methyl-N-[(3-methyloxetan-3-yl)methyl]methanamine + H2O = 2-({[(4-methoxyphenyl)methyl](methyl)amino}methyl)-2-methylpropane-1,3-diol
oxetane = 1,3-propylene oxide = a 4-membered oxygen-containing ring
(13E)-8α-hydroxylabd-13-en-15-yl diphosphate = 8-hydroxycopalyl diphosphate
(1a) ATP + 17-(4-hydroxyphenyl)heptadecanoate = diphosphate + 17-(4-hydroxyphenyl)heptadecanoyl-adenylate
(1b) 17-(4-hydroxyphenyl)heptadecanoyl-adenylate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + 17-(4-hydroxyphenyl)heptadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(2) ATP + 19-(4-hydroxyphenyl)nonadecanoate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + diphosphate + 19-(4-hydroxyphenyl)nonadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
(2a) ATP + 19-(4-hydroxyphenyl)nonadecanoate = diphosphate + 19-(4-hydroxyphenyl)nonadecanoyl-adenylate
(2b) 19-(4-hydroxyphenyl)nonadecanoyl-adenylate + holo-[(phenol)carboxyphthiodiolenone synthase] = AMP + 19-(4-hydroxyphenyl)nonadecanoyl-[(phenol)carboxyphthiodiolenone synthase]
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