The Enzyme Database

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EC 4.2.3.12     
Accepted name: 6-pyruvoyltetrahydropterin synthase
Reaction: 7,8-dihydroneopterin 3′-triphosphate = 6-pyruvoyl-5,6,7,8-tetrahydropterin + triphosphate
For diagram of biopterin biosynthesis, click here
Glossary: 7,8-dihydroneopterin 3′-triphosphate = 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin
Other name(s): 2-amino-4-oxo-6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydroxypteridine triphosphate lyase; 6-[(1S,2R)-1,2-dihydroxy-3-triphosphooxypropyl]-7,8-dihydropterin triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming)
Systematic name: 7,8-dihydroneopterin 3′-triphosphate triphosphate-lyase (6-pyruvoyl-5,6,7,8-tetrahydropterin-forming)
Comments: Catalyses triphosphate elimination and an intramolecular redox reaction in the presence of Mg2+. It has been identified in human liver. This enzyme is involved in the de novo synthesis of tetrahydrobiopterin from GTP, with the other enzymes involved being EC 1.1.1.153 (sepiapterin reductase) and EC 3.5.4.16 (GTP cyclohydrolase I) [3].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 97089-82-2
References:
1.  Milstien, S., Kaufman, S. The biosynthesis of tetrahydrobiopterin in rat brain. Purification and characterization of 6-pyruvoyl-tetrahydrobiopterin(2′-oxo) reductase. J. Biol. Chem. 264 (1989) 8066–8073. [PMID: 2656673]
2.  Thöny, B., Leimbacher, W., Bürgisser, D., Heinzmann, C.W. Human 6-pyruvoyl-tetrahydrobiopterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme. Biochem. Biophys. Res. Commun. 189 (1992) 1437–1443. [DOI] [PMID: 1282802]
3.  Supangat, S., Choi, Y.K., Park, Y.S., Son, D., Han, C.D. and Lee, K.H. Expression, purification, crystallization and preliminary X-ray analysis of sepiapterin reductase from Chlorobium tepidum. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 61 (2005) 202–204. [DOI] [PMID: 16510994]
[EC 4.2.3.12 created 1999 as EC 4.6.1.10, transferred 2000 to EC 4.2.3.12, modified 2001]
 
 
EC 4.2.3.13     
Accepted name: (+)-δ-cadinene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (+)-δ-cadinene + diphosphate
For diagram of cadinane sesquiterpenoid biosynthesis, click here and for diagram of cadinene, cubebol and muuroladiene biosynthesis, click here
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-δ-cadinene-forming)
Comments: The sesquiterpenoid (+)-δ-cadinene is an intermediate in phytoalexin biosynthesis. Mg2+ is required for activity.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 166800-09-5
References:
1.  Chen, X.-Y., Chen, Y., Heinstein, P., Davisson, V.J. Cloning, expression and characterization of (+)-δ-cadinene synthase: a catalyst for cotton phytoalexin biosynthesis. Arch. Biochem. Biophys. 324 (1995) 255–266. [DOI] [PMID: 8554317]
2.  Davis, E.M., Tsuji, J., Davis, G.D., Pierce, M.L., Essenberg, M. Purification of (+)-δ-cadinene synthase, a sesquiterpene cyclase from bacteria-inoculated cotton foliar tissue. Phytochemistry 41 (1996) 1047–1055. [DOI] [PMID: 8728715]
3.  Davis, G.D., Essenberg, M. (+)-δ-Cadinene is a product of sesquiterpene cyclase activity in cotton. Phytochemistry 39 (1995) 553–567.
[EC 4.2.3.13 created 1999 as EC 4.6.1.11, transferred 2000 to EC 4.2.3.13, modified 2011]
 
 
EC 4.2.3.14      
Deleted entry: pinene synthase. Now covered by EC 4.2.3.119, (-)-α-pinene synthase, and EC 4.2.3.120, (-)-β-pinene synthase
[EC 4.2.3.14 created 2000 as EC 4.1.99.8, transferred 2000 to EC 4.2.3.14, deleted 2012]
 
 
EC 4.2.3.15     
Accepted name: myrcene synthase
Reaction: geranyl diphosphate = myrcene + diphosphate
For diagram of monoterpenoid biosynthesis, click here
Glossary: myrcene = 7-methyl-3-methyleneocta-1,6-diene and is a monoterpenoid
Systematic name: geranyl-diphosphate diphosphate-lyase (myrcene-forming)
Comments: A recombinant enzyme (also known as a monoterpene synthase or cyclase) from the grand fir (Abies grandis) requires Mn2+ and K+ for activity. Mg2+ is essentially ineffective as the divalent metal ion cofactor.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 197462-59-2
References:
1.  Bohlmann, J., Steele, C.L. and Croteau, R. Monoterpene synthases from grand fir (Abies grandis). cDNA isolation, characterization, and functional expression of myrcene synthase, (-)-(4S)-limonene synthase, and (-)-(1S,5S)-pinene synthase. J. Biol. Chem. 272 (1997) 21784–21792. [DOI] [PMID: 9268308]
[EC 4.2.3.15 created 2000 as EC 4.1.99.9, transferred 2000 to EC 4.2.3.15]
 
 
EC 4.2.3.16     
Accepted name: (4S)-limonene synthase
Reaction: geranyl diphosphate = (S)-limonene + diphosphate
For diagram of perillyl alcohol, isopiperitol and carveol biosynthesis, click here
Glossary: limonene = a monoterpenoid
(S)-limonene = (-)-limonene
Other name(s): (-)-(4S)-limonene synthase; 4S-(-)-limonene synthase; geranyldiphosphate diphosphate lyase (limonene forming); geranyldiphosphate diphosphate lyase [cyclizing, (4S)-limonene-forming]; geranyl-diphosphate diphosphate-lyase [cyclizing; (-)-(4S)-limonene-forming]
Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing; (S)-limonene-forming]
Comments: A recombinant enzyme (also known as a monoterpene synthase or cyclase) from the grand fir (Abies grandis) requires Mn2+ and K+ for activity. Mg2+ is essentially ineffective as the divalent metal ion cofactor.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 110639-20-8
References:
1.  Bohlmann, J., Steele, C.L. and Croteau, R. Monoterpene synthases from grand fir (Abies grandis). cDNA isolation, characterization, and functional expression of myrcene synthase, (-)-(4S)-limonene synthase, and (-)-(1S,5S)-pinene synthase. J. Biol. Chem. 272 (1997) 21784–21792. [DOI] [PMID: 9268308]
2.  Collby, S.M., Alonso, W.R., Katahira, E.J., McGarvey, D.J. and Croteau, R. 4S-Limonene synthase from the oil glands of spearmint (Mentha spicata). cDNA isolation, characterization, and bacterial expression of the catalytically active monoterpene cyclase. J. Biol. Chem. 268 (1993) 23016–23024. [PMID: 8226816]
3.  Yuba, A., Yazaki, K., Tabata, M., Honda, G. and Croteau, R. cDNA cloning, characterization, and functional expression of 4S-(-)-limonene synthase from Perilla frutescens. Arch. Biochem. Biophys. 332 (1996) 280–287. [DOI] [PMID: 8806736]
[EC 4.2.3.16 created 2000 as EC 4.1.99.10, transferred 2000 to EC 4.2.3.16, modified 2003]
 
 
EC 4.2.3.17     
Accepted name: taxadiene synthase
Reaction: geranylgeranyl diphosphate = taxa-4,11-diene + diphosphate
For diagram of taxadiene biosynthesis, click here
Other name(s): geranylgeranyl-diphosphate diphosphate-lyase (cyclizing, taxadiene-forming)
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (cyclizing; taxa-4,11-diene-forming)
Comments: This is the committed step in the biosynthesis of the diterpenoid antineoplastic drug Taxol (paclitaxel). The cyclization involves a 1,5-hydride shift.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 169277-52-5
References:
1.  Koepp, A.E., Hezari, M., Zajicek, J., Vogel, B.S., LaFever, R.E., Lewis, N.G. and Croteau, R. Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the committed step of taxol biosynthesis in Pacific yew. J. Biol. Chem. 270 (1995) 8686–8690. [DOI] [PMID: 7721772]
2.  Hezari, M., Lewis, N.G. and Croteau, R. Purification and characterization of taxa-4(5),11(12)-diene synthase from Pacific yew (Taxus brevifolia) that catalyzes the first committed step of taxol biosynthesis. Arch. Biochem. Biophys. 322 (1995) 437–444. [DOI] [PMID: 7574719]
3.  Lin, X., Hezari, M., Koepp, A.E., Floss, H.G. and Croteau, R. Mechanism of taxadiene synthase, a diterpene cyclase that catalyzes the first step of taxol biosynthesis in Pacific yew. Biochemistry 35 (1996) 2968–2977. [DOI] [PMID: 8608134]
4.  Hezari, M., Ketchum, R.E., Gibson, D.M. and Croteau, R. Taxol production and taxadiene synthase activity in Taxus canadensis cell suspension cultures. Arch. Biochem. Biophys. 337 (1997) 185. [DOI] [PMID: 9016812]
5.  Williams, D.C., Carroll, B.J., Jin, Q., Rithner, C.D., Lenger, S.R., Floss, H.G., Coates, R.M., Williams, R.M. and Croteau, R. Intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to the taxadiene precursor of taxol catalyzed by recombinant taxadiene synthase. Chem. Biol. 7 (2000) 969–977. [DOI] [PMID: 11137819]
[EC 4.2.3.17 created 2002]
 
 
EC 4.2.3.18     
Accepted name: abieta-7,13-diene synthase
Reaction: (+)-copalyl diphosphate = abieta-7,13-diene + diphosphate
For diagram of abietadiene, abietate, isopimaradiene, phyllocladan-16alpha-ol and sclareol biosynthesis, click here and for diagram of reaction, click here
Glossary: (+)-copalyl diphosphate = (2E)-3-methyl-5-[(1S,4aS,8aS)-5,5,8a-trimethyl-2-methylidenedecahydronaphthalen-1-yl]pent-2-en-1-yl trihydrogen diphosphate
abieta-7,13-diene = (4aS,4bR,10aS)-7-isopropyl-1,1,4a-trimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthrene
Other name(s): copalyl-diphosphate diphosphate-lyase (cyclizing) (ambiguous); abietadiene synthase (ambiguous)
Systematic name: (+)-copalyl-diphosphate diphosphate-lyase [cyclizing, abieta-7,13-diene-forming]
Comments: Part of a bifunctional enzyme involved in the biosynthesis of abietadiene. See also EC 5.5.1.12, copalyl diphosphate synthase. Requires Mg2+.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 157972-08-2
References:
1.  Peters, R.J., Flory, J.E., Jetter, R., Ravn, M.M., Lee, H.J., Coates, R.M. and Croteau, R.B. Abietadiene synthase from grand fir (Abies grandis): characterization and mechanism of action of the "pseudomature" recombinant enzyme. Biochemistry 39 (2000) 15592–15602. [DOI] [PMID: 11112547]
2.  Peters, R.J., Ravn, M.M., Coates, R.M. and Croteau, R.B. Bifunctional abietadiene synthase: free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites. J. Am. Chem. Soc. 123 (2001) 8974–8978. [DOI] [PMID: 11552804]
3.  Peters, R.J. and Croteau, R.B. Abietadiene synthase catalysis: mutational analysis of a prenyl diphosphate ionization-initiated cyclization and rearrangement. Proc. Natl. Acad. Sci. USA 99 (2002) 580–584. [DOI] [PMID: 11805316]
4.  Peters, R.J. and Croteau, R.B. Abietadiene synthase catalysis: conserved residues involved in protonation-initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate. Biochemistry 41 (2002) 1836–1842. [DOI] [PMID: 11827528]
5.  Ravn, M.M., Peters, R.J., Coates, R.M. and Croteau, R. Mechanism of abietadiene synthase catalysis: stereochemistry and stabilization of the cryptic pimarenyl carbocation intermediates. J. Am. Chem. Soc. 124 (2002) 6998–7006. [DOI] [PMID: 12059223]
[EC 4.2.3.18 created 2002, modified 2012]
 
 
EC 4.2.3.19     
Accepted name: ent-kaurene synthase
Reaction: ent-copalyl diphosphate = ent-kaurene + diphosphate
For diagram of the biosynthesis of copalyl diphosphate, abietadiene and ent-kaurene, click here
Other name(s): ent-kaurene synthase B; ent-kaurene synthetase B, ent-copalyl-diphosphate diphosphate-lyase (cyclizing)
Systematic name: ent-copalyl-diphosphate diphosphate-lyase (cyclizing, ent-kaurene-forming)
Comments: Part of a bifunctional enzyme involved in the biosynthesis of ent-kaurene. See also EC 5.5.1.13 (ent-copalyl diphosphate synthase)
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 9055-64-5
References:
1.  Fall, R.R., West, C.A. Purification and properties of kaurene synthetase from Fusarium moniliforme. J. Biol. Chem. 246 (1971) 6913–6928. [PMID: 4331199]
2.  Yamaguchi, S., Saito, T., Abe, H., Yamane, H., Murofushi, N. and Kamiya, Y. Molecular cloning and characterization of a cDNA encoding the gibberellin biosynthetic enzyme ent-kaurene synthase B from pumpkin (Cucurbita maxima L.). Plant J. 10 (1996) 203–213. [DOI] [PMID: 8771778]
3.  Kawaide, H., Imai, R., Sassa, T. and Kamiya, Y. Ent-kaurene synthase from the fungus Phaeosphaeria sp. L487. cDNA isolation, characterization, and bacterial expression of a bifunctional diterpene cyclase in fungal gibberellin biosynthesis. J. Biol. Chem. 272 (1997) 21706–21712. [DOI] [PMID: 9268298]
4.  Toyomasu, T., Kawaide, H., Ishizaki, A., Shinoda, S., Otsuka, M., Mitsuhashi, W. and Sassa, T. Cloning of a full-length cDNA encoding ent-kaurene synthase from Gibberella fujikuroi: functional analysis of a bifunctional diterpene cyclase. Biosci. Biotechnol. Biochem. 64 (2000) 660–664. [DOI] [PMID: 10803977]
[EC 4.2.3.19 created 2002]
 
 
EC 4.2.3.20     
Accepted name: (R)-limonene synthase
Reaction: geranyl diphosphate = (R)-limonene + diphosphate
For diagram of carvone biosynthesis, click here
Glossary: (R)-limonene = (+)-limonene
Other name(s): (+)-limonene synthase; geranyldiphosphate diphosphate lyase [(+)-(R)-limonene-forming]; geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-(4R)-limonene-forming]
Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (R)-limonene-forming]
Comments: Forms the first step of carvone biosynthesis in caraway. The enzyme from Carum carvi (caraway) seeds requires a divalent metal ion (preferably Mn2+) for catalysis. This enzyme occurs in Citrus, Carum (caraway) and Anethum (dill); (-)-limonene, however, is made in the fir, Abies, and mint, Mentha, by EC 4.2.3.16, (4S)-limonene synthase.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 155807-65-1
References:
1.  Bouwmeester, H.J., Gershenzon, J., Konings, M.C.J.M. and Croteau, R. Biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway. I. Demonstration of enzyme activities and their changes with development. Plant Physiol. 117 (1998) 901–912. [PMID: 9662532]
2.  Lücker, J., El Tamer, M.K., Schwab, W., Verstappen, F.W., van der Plas, L.H., Bouwmeester, H.J. and Verhoeven, H.A. Monoterpene biosynthesis in lemon (Citrus limon). cDNA isolation and functional analysis of four monoterpene synthases. Eur. J. Biochem. 269 (2000) 3160–3171. [DOI] [PMID: 12084056]
3.  Maruyama, T., Ito, M., Kiuchi, F. and Honda, G. Molecular cloning, functional expression and characterization of d-limonene synthase from Schizonepeta tenuifolia. Biol. Pharm. Bull. 24 (2001) 373–377. [PMID: 11305598]
[EC 4.2.3.20 created 2003]
 
 
EC 4.2.3.21     
Accepted name: vetispiradiene synthase
Reaction: (2E,6E)-farnesyl diphosphate = vetispiradiene + diphosphate
For diagram of eremophilane and spirovetivane sesquiterpenoid biosynthesis, click here
Other name(s): vetispiradiene-forming farnesyl pyrophosphate cyclase; pemnaspirodiene synthase; HVS; vetispiradiene cyclase
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, vetispiradiene-forming)
Comments: The initial internal cyclization produces the monocyclic intermediate germacrene A.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 192465-18-2
References:
1.  Back, K. and Chappell, J. Cloning and bacterial expression of a sesquiterpene cyclase from Hyoscyamus muticus and its molecular comparison to related terpene cyclases. J. Biol. Chem. 270 (1995) 7375–7381. [DOI] [PMID: 7706281]
2.  Keller, H., Czernic, P., Ponchet, M., Ducrot, P.H., Back, K., Chappell, J., Ricci, P. and Marco, Y. Sesquiterpene cyclase is not a determining factor for elicitor- and pathogen-induced capsidiol accumulation in tobacco. Planta 205 (1998) 467–476.
3.  Mathis, J.R., Back, K., Starks, C., Noel, J., Poulter, C.D. and Chappell, J. Pre-steady-state study of recombinant sesquiterpene cyclases. Biochemistry 36 (1997) 8340–8348. [DOI] [PMID: 9204881]
4.  Yoshioka, H., Yamada, N. and Doke, N. cDNA cloning of sesquiterpene cyclase and squalene synthase, and expression of the genes in potato tuber infected with Phytophthora infestans. Plant Cell Physiol. 40 (1999) 993–998. [PMID: 10588069]
5.  Martin, V.J., Yoshikuni, Y. and Keasling, J.D. The in vivo synthesis of plant sesquiterpenes by Escherichia coli. Biotechnol. Bioeng. 75 (2001) 497–503. [PMID: 11745124]
[EC 4.2.3.21 created 2004, modified 2011]
 
 
EC 4.2.3.22     
Accepted name: germacradienol synthase
Reaction: (2E,6E)-farnesyl diphosphate + H2O = (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol + diphosphate
For diagram of germacrene-derived sesquiterpenoid biosynthesis, click here
Other name(s): germacradienol/germacrene-D synthase; 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase [(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol-forming]
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol-forming]
Comments: Requires Mg2+ for activity. H-1si of farnesyl diphosphate is lost in the formation of (1E,4S,5E,7R)-germacra-1(10),5-dien-11-ol. Formation of (-)-germacrene D involves a stereospecific 1,3-hydride shift of H-1si of farnesyl diphosphate. Both products are formed from a common intermediate [2]. Other enzymes produce germacrene D as the sole product using a different mechanism. The enzyme mediates a key step in the biosynthesis of geosmin (see EC 4.1.99.16 geosmin synthase), a widely occurring metabolite of many streptomycetes, bacteria and fungi [2]. Also catalyses the reaction of EC 4.2.3.75, (-)-germacrene D synthase.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 211049-88-6
References:
1.  Cane, D.E. and Watt, R.M. Expression and mechanistic analysis of a germacradienol synthase from Streptomyces coelicolor implicated in geosmin biosynthesis. Proc. Natl. Acad. Sci. USA 100 (2003) 1547–1551. [DOI] [PMID: 12556563]
2.  He, X. and Cane, D.E. Mechanism and stereochemistry of the germacradienol/germacrene D synthase of Streptomyces coelicolor A3(2). J. Am. Chem. Soc. 126 (2004) 2678–2679. [DOI] [PMID: 14995166]
3.  Gust, B., Challis, G.L., Fowler, K., Kieser, T. and Chater, K.F. PCR-targeted Streptomyces gene replacement identifies a protein domain needed for biosynthesis of the sesquiterpene soil odor geosmin. Proc. Natl. Acad. Sci. USA 100 (2003) 1541–1546. [DOI] [PMID: 12563033]
[EC 4.2.3.22 created 2006, modified 2011]
 
 
EC 4.2.3.23     
Accepted name: germacrene-A synthase
Reaction: (2E,6E)-farnesyl diphosphate = (+)-(R)-gemacrene A + diphosphate
For diagram of germacrene sesquiterpenoid biosynthesis, click here
Other name(s): germacrene A synthase; (+)-germacrene A synthase; (+)-(10R)-germacrene A synthase; GAS; 2-trans,6-trans-farnesyl-diphosphate diphosphate-lyase (germacrene-A-forming)
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-(R)-germacrene-A-forming]
Comments: Requires Mg2+ for activity. While germacrene A is an enzyme-bound intermediate in the biosynthesis of a number of phytoalexins, e.g. EC 4.2.3.9 (aristolochene synthase) from some species and EC 4.2.3.21 (vetispiradiene synthase), it is the sole sesquiterpenoid product formed in chicory [1].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, CAS registry number: 213763-55-4
References:
1.  Bouwmeester, H.J., Kodde, J., Verstappen, F.W., Altug, I.G., de Kraker, J.W. and Wallaart, T.E. Isolation and characterization of two germacrene A synthase cDNA clones from chicory. Plant Physiol. 129 (2002) 134–144. [DOI] [PMID: 12011345]
2.  Prosser, I., Phillips, A.L., Gittings, S., Lewis, M.J., Hooper, A.M., Pickett, J.A. and Beale, M.H. (+)-(10R)-Germacrene A synthase from goldenrod, Solidago canadensis; cDNA isolation, bacterial expression and functional analysis. Phytochemistry 60 (2002) 691–702. [DOI] [PMID: 12127586]
3.  de Kraker, J.W., Franssen, M.C., de Groot, A., König, W.A. and Bouwmeester, H.J. (+)-Germacrene A biosynthesis . The committed step in the biosynthesis of bitter sesquiterpene lactones in chicory. Plant Physiol. 117 (1998) 1381–1392. [PMID: 9701594]
4.  Calvert, M.J., Ashton, P.R. and Allemann, R.K. Germacrene A is a product of the aristolochene synthase-mediated conversion of farnesylpyrophosphate to aristolochene. J. Am. Chem. Soc. 124 (2002) 11636–11641. [DOI] [PMID: 12296728]
5.  Chang, Y.J., Jin, J., Nam, H.Y. and Kim, S.U. Point mutation of (+)-germacrene A synthase from Ixeris dentata. Biotechnol. Lett. 27 (2005) 285–288. [DOI] [PMID: 15834787]
[EC 4.2.3.23 created 2006]
 
 
EC 4.2.3.24     
Accepted name: amorpha-4,11-diene synthase
Reaction: (2E,6E)-farnesyl diphosphate = amorpha-4,11-diene + diphosphate
Other name(s): amorphadiene synthase
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (amorpha-4,11-diene-forming)
Comments: Requires Mg2+ and Mn2+ for activity. This is a key enzyme in the biosynthesis of the antimalarial endoperoxide artemisinin [3]. Catalyses the formation of both olefinic [e.g. amorpha-4,11-diene, amorpha-4,7(11)-diene, γ-humulene and β-sesquiphellandrene] and oxygenated (e.g. amorpha-4-en-7-ol) sesquiterpenes, with amorpha-4,11-diene being the major product. When geranyl diphosphate is used as a substrate, no monoterpenes are produced [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 259213-60-0
References:
1.  Wallaart, T.E., Bouwmeester, H.J., Hille, J., Poppinga, L. and Maijers, N.C. Amorpha-4,11-diene synthase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin. Planta 212 (2001) 460–465. [DOI] [PMID: 11289612]
2.  Mercke, P., Bengtsson, M., Bouwmeester, H.J., Posthumus, M.A. and Brodelius, P.E. Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Arch. Biochem. Biophys. 381 (2000) 173–180. [DOI] [PMID: 11032404]
3.  Bouwmeester, H.J., Wallaart, T.E., Janssen, M.H., van Loo, B., Jansen, B.J., Posthumus, M.A., Schmidt, C.O., De Kraker, J.W., König, W.A. and Franssen, M.C. Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52 (1999) 843–854. [DOI] [PMID: 10626375]
4.  Chang, Y.J., Song, S.H., Park, S.H. and Kim, S.U. Amorpha-4,11-diene synthase of Artemisia annua: cDNA isolation and bacterial expression of a terpene synthase involved in artemisinin biosynthesis. Arch. Biochem. Biophys. 383 (2000) 178–184. [DOI] [PMID: 11185551]
5.  Martin, V.J., Pitera, D.J., Withers, S.T., Newman, J.D. and Keasling, J.D. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Nat. Biotechnol. 21 (2003) 796–802. [DOI] [PMID: 12778056]
6.  Picaud, S., Mercke, P., He, X., Sterner, O., Brodelius, M., Cane, D.E. and Brodelius, P.E. Amorpha-4,11-diene synthase: Mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate. Arch. Biochem. Biophys. 448 (2006) 150–155. [DOI] [PMID: 16143293]
[EC 4.2.3.24 created 2006]
 
 
EC 4.2.3.25     
Accepted name: S-linalool synthase
Reaction: geranyl diphosphate + H2O = (3S)-linalool + diphosphate
For diagram of acyclic monoterpenoid biosynthesis, click here
Glossary: (3S)-linalool = (3S)-3,7-dimethylocta-1,6-dien-3-ol
Other name(s): LIS; Lis; 3S-linalool synthase
Systematic name: geranyl-diphosphate diphosphate-lyase [(3S)-linalool-forming]
Comments: Requires Mn2+ or Mg2+ for activity. Neither (S)- nor (R)-linalyl diphosphate can act as substrate for the enzyme from the flower Clarkia breweri [1]. Unlike many other monoterpene synthases, only a single product, (3S)-linalool, is formed.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, CAS registry number: 160477-81-6
References:
1.  Pichersky, E., Lewinsohn, E. and Croteau, R. Purification and characterization of S-linalool synthase, an enzyme involved in the production of floral scent in Clarkia breweri. Arch. Biochem. Biophys. 316 (1995) 803–807. [DOI] [PMID: 7864636]
2.  Lücker, J., Bouwmeester, H.J., Schwab, W., Blaas, J., van der Plas, L.H. and Verhoeven, H.A. Expression of Clarkia S-linalool synthase in transgenic petunia plants results in the accumulation of S-linalyl-β-D-glucopyranoside. Plant J. 27 (2001) 315–324. [DOI] [PMID: 11532177]
3.  Dudareva, N., Cseke, L., Blanc, V.M. and Pichersky, E. Evolution of floral scent in Clarkia: novel patterns of S-linalool synthase gene expression in the C. breweri flower. Plant Cell 8 (1996) 1137–1148. [DOI] [PMID: 8768373]
[EC 4.2.3.25 created 2006]
 
 
EC 4.2.3.26     
Accepted name: R-linalool synthase
Reaction: geranyl diphosphate + H2O = (3R)-linalool + diphosphate
For diagram of acyclic monoterpenoid biosynthesis, click here
Glossary: (3R)-linalool = (3R)-3,7-dimethylocta-1,6-dien-3-ol
Other name(s): (3R)-linalool synthase; (–)-3R-linalool synthase
Systematic name: geranyl-diphosphate diphosphate-lyase [(3R)-linalool-forming]
Comments: Geranyl diphosphate cannot be replaced by isopentenyl diphosphate (3-methylbut-3-en-1-yl diphosphate), prenyl diphosphate, farnesyl diphosphate or geranylgeranyl diphosphate as substrate [1]. Requires Mg2+ or Mn2+ for activity. Unlike many other monoterpene synthases, only a single product, (3R)-linalool, is formed.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 254993-26-5
References:
1.  Jia, J.W., Crock, J., Lu, S., Croteau, R. and Chen, X.Y. (3R)-Linalool synthase from Artemisia annua L.: cDNA isolation, characterization, and wound induction. Arch. Biochem. Biophys. 372 (1999) 143–149. [DOI] [PMID: 10562427]
2.  Crowell, A.L., Williams, D.C., Davis, E.M., Wildung, M.R. and Croteau, R. Molecular cloning and characterization of a new linalool synthase. Arch. Biochem. Biophys. 405 (2002) 112–121. [DOI] [PMID: 12176064]
[EC 4.2.3.26 created 2006]
 
 
EC 4.2.3.27     
Accepted name: isoprene synthase
Reaction: prenyl diphosphate = isoprene + diphosphate
For diagram of isoprene biosynthesis and metabolism, click here
Glossary: isoprene = 2-methylbuta-1,3-diene
Other name(s): ISPC; ISPS; dimethylallyl-diphosphate diphosphate-lyase (isoprene-forming)
Systematic name: prenyl-diphosphate diphosphate-lyase (isoprene-forming)
Comments: Requires Mg2+ or Mn2+ for activity. This enzyme is located in the chloroplast of isoprene-emitting plants, such as poplar and aspen, and may be activitated by light-dependent changes in chloroplast pH and Mg2+ concentration [2,8].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 139172-14-8
References:
1.  Silver, G.M. and Fall, R. Enzymatic synthesis of isoprene from dimethylallyl diphosphate in aspen leaf extracts. Plant Physiol. 97 (1991) 1588–1591. [PMID: 16668590]
2.  Silver, G.M. and Fall, R. Characterization of aspen isoprene synthase, an enzyme responsible for leaf isoprene emission to the atmosphere. J. Biol. Chem. 270 (1995) 13010–13016. [DOI] [PMID: 7768893]
3.  Wildermuth, M.C. and Fall, R. Light-dependent isoprene emission (characterization of a thylakoid-bound isoprene synthase in Salix discolor chloroplasts). Plant Physiol. 112 (1996) 171–182. [PMID: 12226383]
4.  Schnitzler, J.P., Arenz, R., Steinbrecher, R. and Lehming, A. Characterization of an isoprene synthase from leaves of Quercus petraea. Bot. Acta 109 (1996) 216–221.
5.  Miller, B., Oschinski, C. and Zimmer, W. First isolation of an isoprene synthase gene from poplar and successful expression of the gene in Escherichia coli. Planta 213 (2001) 483–487. [PMID: 11506373]
6.  Sivy, T.L., Shirk, M.C. and Fall, R. Isoprene synthase activity parallels fluctuations of isoprene release during growth of Bacillus subtilis. Biochem. Biophys. Res. Commun. 294 (2002) 71–75. [DOI] [PMID: 12054742]
7.  Sasaki, K., Ohara, K. and Yazaki, K. Gene expression and characterization of isoprene synthase from Populus alba. FEBS Lett. 579 (2005) 2514–2518. [DOI] [PMID: 15848197]
8.  Schnitzler, J.-P., Zimmer, I., Bachl, A., Arend, M., Fromm, J. and Fischbach, R.J. Biochemical properties of isoprene synthase in poplar (Populus x canescens). Planta 222 (2005) 777–786. [DOI] [PMID: 16052321]
[EC 4.2.3.27 created 2007]
 
 
EC 4.2.3.28     
Accepted name: ent-cassa-12,15-diene synthase
Reaction: ent-copalyl diphosphate = ent-cassa-12,15-diene + diphosphate
For diagram of the biosynthesis of diterpenoids from ent-copalyl diphosphate, click here
Other name(s): OsDTC1; OsKS7
Systematic name: ent-copalyl-diphosphate diphosphate-lyase (ent-cassa-12,15-diene-forming)
Comments: This class I diterpene cyclase produces ent-cassa-12,15-diene, a precursor of the rice phytoalexins (-)-phytocassanes A-E. Phytoalexins are diterpenoid secondary metabolites that are involved in the defense mechanism of the plant, and are produced in response to pathogen attack through the perception of elicitor signal molecules such as chitin oligosaccharide, or after exposure to UV irradiation.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Cho, E.M., Okada, A., Kenmoku, H., Otomo, K., Toyomasu, T., Mitsuhashi, W., Sassa, T., Yajima, A., Yabuta, G., Mori, K., Oikawa, H., Toshima, H., Shibuya, N., Nojiri, H., Omori, T., Nishiyama, M. and Yamane, H. Molecular cloning and characterization of a cDNA encoding ent-cassa-12,15-diene synthase, a putative diterpenoid phytoalexin biosynthetic enzyme, from suspension-cultured rice cells treated with a chitin elicitor. Plant J. 37 (2004) 1–8. [DOI] [PMID: 14675427]
[EC 4.2.3.28 created 2008]
 
 
EC 4.2.3.29     
Accepted name: ent-sandaracopimaradiene synthase
Reaction: ent-copalyl diphosphate = ent-sandaracopimara-8(14),15-diene + diphosphate
For diagram of the biosynthesis of diterpenoids from ent-copalyl diphosphate, click here
Other name(s): OsKS10; ent-sandaracopimara-8(14),15-diene synthase
Systematic name: ent-copalyl-diphosphate diphosphate-lyase [ent-sandaracopimara-8(14),15-diene-forming]
Comments: ent-Sandaracopimaradiene is a precursor of the rice oryzalexins A-F. Phytoalexins are diterpenoid secondary metabolites that are involved in the defense mechanism of the plant, and are produced in response to pathogen attack through the perception of elicitor signal molecules such as chitin oligosaccharide, or after exposure to UV irradiation. As a minor product, this enzyme also forms ent-pimara-8(14),15-diene, which is the sole product of EC 4.2.3.30, ent-pimara-8(14),15-diene synthase. ent-Pimara-8(14),15-diene is not a precursor in the biosynthesis of either gibberellins or phytoalexins [2].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Otomo, K., Kanno, Y., Motegi, A., Kenmoku, H., Yamane, H., Mitsuhashi, W., Oikawa, H., Toshima, H., Itoh, H., Matsuoka, M., Sassa, T. and Toyomasu, T. Diterpene cyclases responsible for the biosynthesis of phytoalexins, momilactones A, B, and oryzalexins A-F in rice. Biosci. Biotechnol. Biochem. 68 (2004) 2001–2006. [DOI] [PMID: 15388982]
2.  Kanno, Y., Otomo, K., Kenmoku, H., Mitsuhashi, W., Yamane, H., Oikawa, H., Toshima, H., Matsuoka, M., Sassa, T. and Toyomasu, T. Characterization of a rice gene family encoding type-A diterpene cyclases. Biosci. Biotechnol. Biochem. 70 (2006) 1702–1710. [DOI] [PMID: 16861806]
[EC 4.2.3.29 created 2008]
 
 
EC 4.2.3.30     
Accepted name: ent-pimara-8(14),15-diene synthase
Reaction: ent-copalyl diphosphate = ent-pimara-8(14),15-diene + diphosphate
For diagram of the biosynthesis of diterpenoids from ent-copalyl diphosphate, click here
Other name(s): OsKS5
Systematic name: ent-copalyl-diphosphate diphosphate-lyase [ent-pimara-8(14),15-diene-forming]
Comments: Unlike EC 4.2.3.29, ent-sandaracopimaradiene synthase, which can produce both ent-sandaracopimaradiene and ent-pimara-8(14),15-diene, this diterpene cyclase produces only ent-pimara-8(14),15-diene. ent-Pimara-8(14),15-diene is not a precursor in the biosynthesis of either gibberellins or phytoalexins.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Kanno, Y., Otomo, K., Kenmoku, H., Mitsuhashi, W., Yamane, H., Oikawa, H., Toshima, H., Matsuoka, M., Sassa, T. and Toyomasu, T. Characterization of a rice gene family encoding type-A diterpene cyclases. Biosci. Biotechnol. Biochem. 70 (2006) 1702–1710. [DOI] [PMID: 16861806]
[EC 4.2.3.30 created 2008]
 
 
EC 4.2.3.31     
Accepted name: ent-pimara-9(11),15-diene synthase
Reaction: ent-copalyl diphosphate = ent-pimara-9(11),15-diene + diphosphate
For diagram of the biosynthesis of diterpenoids from ent-copalyl diphosphate, click here
Other name(s): PMD synthase
Systematic name: ent-copalyl-diphosphate diphosphate-lyase [ent-pimara-9(11),15-diene-forming]
Comments: This enzyme is involved in the biosynthesis of the diterpenoid viguiepinol and requires Mg2+, Co2+, Zn2+ or Ni2+ for activity.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Ikeda, C., Hayashi, Y., Itoh, N., Seto, H. and Dairi, T. Functional analysis of eubacterial ent-copalyl diphosphate synthase and pimara-9(11),15-diene synthase with unique primary sequences. J. Biochem. 141 (2007) 37–45. [DOI] [PMID: 17148547]
[EC 4.2.3.31 created 2008]
 
 
EC 4.2.3.32     
Accepted name: levopimaradiene synthase
Reaction: (+)-copalyl diphosphate = abieta-8(14),12-diene + diphosphate
For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here and for diagram of abietadiene, levopimaradiene and isopimara-7,15-diene biosynthesis, click here
Glossary: levopimaradiene = abieta-8(14),12-diene
Other name(s): PtTPS-LAS; LPS; copalyl-diphosphate diphosphate-lyase [abieta-8(14),12-diene-forming]
Systematic name: (+)-copalyl-diphosphate diphosphate-lyase [abieta-8(14),12-diene-forming]
Comments: In Ginkgo, the enzyme catalyses the initial cyclization step in the biosynthesis of ginkgolides, a structurally unique family of diterpenoids that are highly specific platelet-activating-factor receptor antagonists [1]. Levopimaradiene is widely distributed in higher plants. In some species the enzyme also forms abietadiene, palustradiene, and neoabietadiene [2].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Schepmann, H.G., Pang, J. and Matsuda, S.P. Cloning and characterization of Ginkgo biloba levopimaradiene synthase which catalyzes the first committed step in ginkgolide biosynthesis. Arch. Biochem. Biophys. 392 (2001) 263–269. [DOI] [PMID: 11488601]
2.  Ro, D.K. and Bohlmann, J. Diterpene resin acid biosynthesis in loblolly pine (Pinus taeda): functional characterization of abietadiene/levopimaradiene synthase (PtTPS-LAS) cDNA and subcellular targeting of PtTPS-LAS and abietadienol/abietadienal oxidase (PtAO, CYP720B1). Phytochemistry 67 (2006) 1572–1578. [DOI] [PMID: 16497345]
[EC 4.2.3.32 created 2008, modified 2012]
 
 
EC 4.2.3.33     
Accepted name: stemar-13-ene synthase
Reaction: 9α-copalyl diphosphate = stemar-13-ene + diphosphate
For diagram of the biosynthesis of diterpenoids from 9alpha-copalyl diphosphate, click here
Glossary: syn-copalyl diphosphate = 9α-copalyl diphosphate
Other name(s): OsDTC2; OsK8; OsKL8; OsKS8; stemarene synthase; syn-stemar-13-ene synthase
Systematic name: 9α-copalyl-diphosphate diphosphate-lyase (stemar-13-ene-forming)
Comments: This diterpene cyclase produces stemar-13-ene, a putative precursor of the rice phytoalexin oryzalexin S. Phytoalexins are diterpenoid secondary metabolites that are involved in the defense mechanism of the plant, and are produced in response to pathogen attack through the perception of elicitor signal molecules such as chitin oligosaccharide, or after exposure to UV irradiation.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Mohan, R.S., Yee, N.K., Coates, R.M., Ren, Y.Y., Stamenkovic, P., Mendez, I. and West, C.A. Biosynthesis of cyclic diterpene hydrocarbons in rice cell suspensions: conversion of 9,10-syn-labda-8(17),13-dienyl diphosphate to 9β-pimara-7,15-diene and stemar-13-ene. Arch. Biochem. Biophys. 330 (1996) 33–47. [DOI] [PMID: 8651702]
2.  Nemoto, T., Cho, E.M., Okada, A., Okada, K., Otomo, K., Kanno, Y., Toyomasu, T., Mitsuhashi, W., Sassa, T., Minami, E., Shibuya, N., Nishiyama, M., Nojiri, H. and Yamane, H. Stemar-13-ene synthase, a diterpene cyclase involved in the biosynthesis of the phytoalexin oryzalexin S in rice. FEBS Lett. 571 (2004) 182–186. [DOI] [PMID: 15280039]
[EC 4.2.3.33 created 2008]
 
 
EC 4.2.3.34     
Accepted name: stemod-13(17)-ene synthase
Reaction: 9α-copalyl diphosphate = stemod-13(17)-ene + diphosphate
For diagram of the biosynthesis of diterpenoids from 9alpha-copalyl diphosphate, click here
Glossary: syn-copalyl diphosphate = 9α-copalyl diphosphate
exo-stemodene = stemod-13(17)-ene
Other name(s): OsKSL11; stemodene synthase
Systematic name: 9α-copalyl-diphosphate diphosphate-lyase [stemod-13(17)-ene-forming]
Comments: This enzyme catalyses the committed step in the biosynthesis of the stemodane family of diterpenoid secondary metabolites, some of which possess mild antiviral activity. The enzyme also produces stemod-12-ene and stemar-13-ene as minor products.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Morrone, D., Jin, Y., Xu, M., Choi, S.Y., Coates, R.M. and Peters, R.J. An unexpected diterpene cyclase from rice: functional identification of a stemodene synthase. Arch. Biochem. Biophys. 448 (2006) 133–140. [DOI] [PMID: 16256063]
[EC 4.2.3.34 created 2008]
 
 
EC 4.2.3.35     
Accepted name: syn-pimara-7,15-diene synthase
Reaction: 9α-copalyl diphosphate = 9β-pimara-7,15-diene + diphosphate
For diagram of the biosynthesis of diterpenoids from 9alpha-copalyl diphosphate, click here
Glossary: syn-copalyl diphosphate = 9α-copalyl diphosphate
syn-pimara-7,15-diene = 9β-pimara-7,15-diene
Other name(s): 9β-pimara-7,15-diene synthase; OsDTS2; OsKS4
Systematic name: 9α-copalyl-diphosphate diphosphate-lyase (9β-pimara-7,15-diene-forming)
Comments: This enzyme is a class I terpene synthase [1]. 9β-Pimara-7,15-diene is a precursor of momilactones A and B, rice diterpenoid phytoalexins that are produced in response to attack (by a pathogen, elicitor or UV irradiation) and are involved in the defense mechanism of the plant. Momilactone B can also act as an allochemical, being constitutively produced in the root of the plant and secreted to the rhizosphere where it suppresses the growth of neighbouring plants and soil microorganisms [1].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Wilderman, P.R., Xu, M., Jin, Y., Coates, R.M. and Peters, R.J. Identification of syn-pimara-7,15-diene synthase reveals functional clustering of terpene synthases involved in rice phytoalexin/allelochemical biosynthesis. Plant Physiol. 135 (2004) 2098–2105. [DOI] [PMID: 15299118]
2.  Otomo, K., Kanno, Y., Motegi, A., Kenmoku, H., Yamane, H., Mitsuhashi, W., Oikawa, H., Toshima, H., Itoh, H., Matsuoka, M., Sassa, T. and Toyomasu, T. Diterpene cyclases responsible for the biosynthesis of phytoalexins, momilactones A, B, and oryzalexins A-F in rice. Biosci. Biotechnol. Biochem. 68 (2004) 2001–2006. [DOI] [PMID: 15388982]
[EC 4.2.3.35 created 2008]
 
 
EC 4.2.3.36     
Accepted name: terpentetriene synthase
Reaction: terpentedienyl diphosphate = terpentetriene + diphosphate
For diagram of diterpenoid biosynthesis, click here
Other name(s): Cyc2 (ambiguous)
Systematic name: terpentedienyl-diphosphate diphosphate-lyase (terpentetriene-forming)
Comments: Requires Mg2+ for maximal activity but can use Mn2+, Fe2+ or Co2+ to a lesser extent [2]. Following on from EC 5.5.1.15, terpentedienyl-diphosphate synthase, this enzyme completes the transformation of geranylgeranyl diphosphate (GGDP) into terpentetriene, which is a precursor of the diterpenoid antibiotic terpentecin. Farnesyl diphosphate can also act as a substrate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Dairi, T., Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K. and Seto, H. Eubacterial diterpene cyclase genes essential for production of the isoprenoid antibiotic terpentecin. J. Bacteriol. 183 (2001) 6085–6094. [DOI] [PMID: 11567009]
2.  Hamano, Y., Kuzuyama, T., Itoh, N., Furihata, K., Seto, H. and Dairi, T. Functional analysis of eubacterial diterpene cyclases responsible for biosynthesis of a diterpene antibiotic, terpentecin. J. Biol. Chem. 277 (2002) 37098–37104. [DOI] [PMID: 12138123]
3.  Eguchi, T., Dekishima, Y., Hamano, Y., Dairi, T., Seto, H. and Kakinuma, K. A new approach for the investigation of isoprenoid biosynthesis featuring pathway switching, deuterium hyperlabeling, and 1H NMR spectroscopy. The reaction mechanism of a novel streptomyces diterpene cyclase. J. Org. Chem. 68 (2003) 5433–5438. [DOI] [PMID: 12839434]
[EC 4.2.3.36 created 2008]
 
 
EC 4.2.3.37     
Accepted name: epi-isozizaene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (+)-epi-isozizaene + diphosphate
For diagram of biosynthesis of tricyclic sesquiterpenoids derived from bisabolyl cation, click here and for diagram of bisabolene derived sesquiterpenoid biosynthesis, click here
Other name(s): SCO5222 protein
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-epi-isozizaene-forming]
Comments: Requires Mg2+ for activity. The displacement of the diphosphate group of farnesyl diphosphate occurs with retention of configuration [1]. In the soil-dwelling bacterium Streptomyces coelicolor A3(2), the product of this reaction is used by EC 1.14.15.39, epi-isozizaene 5-monooxygenase, to produce the sesquiterpene antibiotic albaflavenone [2].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB
References:
1.  Lin, X., Hopson, R. and Cane, D.E. Genome mining in Streptomyces coelicolor: molecular cloning and characterization of a new sesquiterpene synthase. J. Am. Chem. Soc. 128 (2006) 6022–6023. [DOI] [PMID: 16669656]
2.  Zhao, B., Lin, X., Lei, L., Lamb, D.C., Kelly, S.L., Waterman, M.R. and Cane, D.E. Biosynthesis of the sesquiterpene antibiotic albaflavenone in Streptomyces coelicolor A3(2). J. Biol. Chem. 283 (2008) 8183–8189. [DOI] [PMID: 18234666]
[EC 4.2.3.37 created 2008]
 
 
EC 4.2.3.38     
Accepted name: α-bisabolene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (E)-α-bisabolene + diphosphate
For diagram of bisabolene-derived sesquiterpenoid biosynthesis, click here
Other name(s): bisabolene synthase
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(E)-α-bisabolene-forming]
Comments: This cytosolic sesquiterpenoid synthase requires a divalent cation cofactor (Mg2+ or, to a lesser extent, Mn2+) to neutralize the negative charge of the diphosphate leaving group. While unlikely to encounter geranyl diphosphate (GDP) in vivo as it is localized to plastids, the enzyme can use GDP as a substrate in vitro to produce (+)-(4R)-limonene [cf. EC 4.2.3.20, (R)-limonene synthase]. The enzyme is induced as part of a defense mechanism in the grand fir Abies grandis as a response to stem wounding.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Bohlmann, J., Crock, J., Jetter, R. and Croteau, R. Terpenoid-based defenses in conifers: cDNA cloning, characterization, and functional expression of wound-inducible (E)-α-bisabolene synthase from grand fir (Abies grandis). Proc. Natl. Acad. Sci. USA 95 (1998) 6756–6761. [DOI] [PMID: 9618485]
[EC 4.2.3.38 created 2009]
 
 
EC 4.2.3.39     
Accepted name: epi-cedrol synthase
Reaction: (2E,6E)-farnesyl diphosphate + H2O = 8-epi-cedrol + diphosphate
For diagram of bisabolene-derived sesquiterpenoid biosynthesis, click here
Other name(s): 8-epicedrol synthase; epicedrol synthase
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (8-epi-cedrol-forming)
Comments: The enzyme is activated by Mg2+ [2]. Similar to many other plant terpenoid synthases, this enzyme produces many products from a single substrate. The predominant product is the cyclic sesquiterpenoid alcohol, 8-epi-cedrol, with minor products including cedrol and the olefins α-cedrene, β-cedrene, (E)-β-farnesene and (E)-α-bisabolene [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Mercke, P., Crock, J., Croteau, R. and Brodelius, P.E. Cloning, expression, and characterization of epi-cedrol synthase, a sesquiterpene cyclase from Artemisia annua L. Arch. Biochem. Biophys. 369 (1999) 213–222. [DOI] [PMID: 10486140]
2.  Hua, L. and Matsuda, S.P. The molecular cloning of 8-epicedrol synthase from Artemisia annua. Arch. Biochem. Biophys. 369 (1999) 208–212. [DOI] [PMID: 10486139]
[EC 4.2.3.39 created 2009]
 
 
EC 4.2.3.40     
Accepted name: (Z)-γ-bisabolene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (Z)-γ-bisabolene + diphosphate
For diagram of bisabolene-derived sesquiterpenoid biosynthesis, click here
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(Z)-γ-bisabolene-forming]
Comments: This sesquiterpenoid enzyme is constitutively expressed in the root, hydathodes and stigma of the plant Arabidopsis thaliana. If the leaves of the plant are wounded, e.g. by cutting, the enzyme is also induced close to the wound site. The sesquiterpenoids (E)-nerolidol and α-bisabolol are also produced by this enzyme as minor products.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB
References:
1.  Ro, D.K., Ehlting, J., Keeling, C.I., Lin, R., Mattheus, N. and Bohlmann, J. Microarray expression profiling and functional characterization of AtTPS genes: duplicated Arabidopsis thaliana sesquiterpene synthase genes At4g13280 and At4g13300 encode root-specific and wound-inducible (Z)-γ-bisabolene synthases. Arch. Biochem. Biophys. 448 (2006) 104–116. [DOI] [PMID: 16297850]
[EC 4.2.3.40 created 2009]
 
 
EC 4.2.3.41     
Accepted name: elisabethatriene synthase
Reaction: geranylgeranyl diphosphate = elisabethatriene + diphosphate
For diagram of diterpenoid biosynthesis, click here and for reaction mechanism, click here
Other name(s): elisabethatriene cyclase
Systematic name: geranylgeranyl-diphosphate diphosphate-lyase (elisabethatriene-forming)
Comments: Requires Mg2+ or less efficiently Mn2+. The enzyme is also able to use farnesyl diphosphate and geranyl diphosphate.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 334022-59-2
References:
1.  Kohl, A.C. and Kerr, R.G. Identification and characterization of the pseudopterosin diterpene cyclase, elisabethatriene synthase, from the marine gorgonian, Pseudopterogorgia elisabethae. Arch. Biochem. Biophys. 424 (2004) 97–104. [DOI] [PMID: 15019841]
2.  Bruck, T.B. and Kerr, R.G. Purification and kinetic properties of elisabethatriene synthase from the coral Pseudopterogorgia elisabethae. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 143 (2006) 269–278. [DOI] [PMID: 16423548]
[EC 4.2.3.41 created 2009]
 
 
EC 4.2.3.42     
Accepted name: aphidicolan-16β-ol synthase
Reaction: 9α-copalyl diphosphate + H2O = aphidicolan-16β-ol + diphosphate
For diagram of diterpenoid biosynthesis, click here and for reaction mechanism, click here
Other name(s): PbACS
Systematic name: 9α-copalyl-diphosphate diphosphate-lyase (aphidicolan-16β-ol-forming)
Comments: This is a bifunctional enzyme which also has EC 5.5.1.14 syn-copalyl diphosphate synthase activity. Aphidicolan-16β-ol is a precursor of aphidicolin, a specific inhibitor of DNA polymerase α (EC 2.7.7.7).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Oikawa, H., Toyomasu, T., Toshima, H., Ohashi, S., Kawaide, H., Kamiya, Y., Ohtsuka, M., Shinoda, S., Mitsuhashi, W. and Sassa, T. Cloning and functional expression of cDNA encoding aphidicolan-16 β-ol synthase: a key enzyme responsible for formation of an unusual diterpene skeleton in biosynthesis of aphidicolin. J. Am. Chem. Soc. 123 (2001) 5154–5155. [PMID: 11457369]
2.  Toyomasu, T., Nakaminami, K., Toshima, H., Mie, T., Watanabe, K., Ito, H., Matsui, H., Mitsuhashi, W., Sassa, T. and Oikawa, H. Cloning of a gene cluster responsible for the biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA polymerase α. Biosci. Biotechnol. Biochem. 68 (2004) 146–152. [DOI] [PMID: 14745177]
[EC 4.2.3.42 created 2009]
 
 
EC 4.2.3.43     
Accepted name: fusicocca-2,10(14)-diene synthase
Reaction: geranylgeranyl diphosphate = fusicocca-2,10(14)-diene + diphosphate
For diagram of diterpenoid biosynthesis, click here and for reaction mechanism, click here
Other name(s): fusicoccadiene synthase; PaFS; PaDC4
Systematic name: geranylgeranyl diphosphate-lyase (fusicocca-2,10(14)-diene-forming)
Comments: A multifunctional enzyme with EC 2.5.1.29 farnesyltranstransferase activity.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Toyomasu, T., Tsukahara, M., Kaneko, A., Niida, R., Mitsuhashi, W., Dairi, T., Kato, N. and Sassa, T. Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi. Proc. Natl. Acad. Sci. USA 104 (2007) 3084–3088. [DOI] [PMID: 17360612]
[EC 4.2.3.43 created 2009]
 
 
EC 4.2.3.44     
Accepted name: isopimara-7,15-diene synthase
Reaction: (+)-copalyl diphosphate = isopimara-7,15-diene + diphosphate
For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here and for diagram of abietadiene, levopimaradiene and isopimara-7,15-diene biosynthesis, click here
Glossary: isopimara-7,15-diene = 13α-pimara-7,15-diene
Other name(s): PaTPS-Iso; copalyl diphosphate-lyase (isopimara-7,15-diene-forming)
Systematic name: (+)-copalyl diphosphate-lyase (isopimara-7,15-diene-forming)
Comments: The enzyme only gave isopimara-7,15-diene.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Martin, D.M., Faldt, J. and Bohlmann, J. Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily. Plant Physiol. 135 (2004) 1908–1927. [DOI] [PMID: 15310829]
[EC 4.2.3.44 created 2009]
 
 
EC 4.2.3.45     
Accepted name: phyllocladan-16α-ol synthase
Reaction: (+)-copalyl diphosphate + H2O = phyllocladan-16α-ol + diphosphate
For diagram of abietadiene, aphidicolanol, sclareol and terpentetriene biosynthesis, click here and for mechanism of reaction, click here
Other name(s): PaDC1
Systematic name: (+)-copalyl-diphosphate diphosphate-lyase (phyllocladan-16α-ol-forming)
Comments: The adjacent gene PaDC2 codes EC 5.5.1.12 copalyl diphosphate synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Toyomasu, T., Niida, R., Kenmoku, H., Kanno, Y., Miura, S., Nakano, C., Shiono, Y., Mitsuhashi, W., Toshima, H., Oikawa, H., Hoshino, T., Dairi, T., Kato, N. and Sassa, T. Identification of diterpene biosynthetic gene clusters and functional analysis of labdane-related diterpene cyclases in Phomopsis amygdali. Biosci. Biotechnol. Biochem. 72 (2008) 1038–1047. [DOI] [PMID: 18391465]
[EC 4.2.3.45 created 2009]
 
 
EC 4.2.3.46     
Accepted name: α-farnesene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (3E,6E)-α-farnesene + diphosphate
For diagram of acyclic sesquiterpenoid biosynthesis, click here
Other name(s): (E,E)-α-farnesene synthase; AFS1; MdAFS1
Systematic name: (2E,6E)-farnesyl-diphosphate lyase [(3E,6E)-α-farnesene-forming]
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Pechous, S.W. and Whitaker, B.D. Cloning and functional expression of an (E,E)-α-farnesene synthase cDNA from peel tissue of apple fruit. Planta 219 (2004) 84–94. [DOI] [PMID: 14740213]
2.  Green, S., Squire, C.J., Nieuwenhuizen, N.J., Baker, E.N. and Laing, W. Defining the potassium binding region in an apple terpene synthase. J. Biol. Chem. 284 (2009) 8661–8669. [DOI] [PMID: 19181671]
3.  Nieuwenhuizen, N.J., Wang, M.Y., Matich, A.J., Green, S.A., Chen, X., Yauk, Y.K., Beuning, L.L., Nagegowda, D.A., Dudareva, N. and Atkinson, R.G. Two terpene synthases are responsible for the major sesquiterpenes emitted from the flowers of kiwifruit (Actinidia deliciosa). J. Exp. Bot. 60 (2009) 3203–3219. [DOI] [PMID: 19516075]
[EC 4.2.3.46 created 2010]
 
 
EC 4.2.3.47     
Accepted name: β-farnesene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (E)-β-farnesene + diphosphate
For diagram of acyclic sesquiterpenoid biosynthesis, click here
Other name(s): farnesene synthase; terpene synthase 10; terpene synthase 10-B73; TPS10
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(E)-β-farnesene-forming]
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB
References:
1.  Zhao, B., Lei, L., Vassylyev, D.G., Lin, X., Cane, D.E., Kelly, S.L., Yuan, H., Lamb, D.C. and Waterman, M.R. Crystal structure of albaflavenone monooxygenase containing a moonlighting terpene synthase active site. J. Biol. Chem. 284 (2009) 36711–36719. [DOI] [PMID: 19858213]
2.  Picaud, S., Brodelius, M. and Brodelius, P.E. Expression, purification and characterization of recombinant (E)-β-farnesene synthase from Artemisia annua. Phytochemistry 66 (2005) 961–967. [DOI] [PMID: 15896363]
3.  Kollner, T.G., Gershenzon, J. and Degenhardt, J. Molecular and biochemical evolution of maize terpene synthase 10, an enzyme of indirect defense. Phytochemistry 70 (2009) 1139–1145. [DOI] [PMID: 19646721]
4.  Schnee, C., Kollner, T.G., Held, M., Turlings, T.C., Gershenzon, J. and Degenhardt, J. The products of a single maize sesquiterpene synthase form a volatile defense signal that attracts natural enemies of maize herbivores. Proc. Natl. Acad. Sci. USA 103 (2006) 1129–1134. [DOI] [PMID: 16418295]
5.  Maruyama, T., Ito, M. and Honda, G. Molecular cloning, functional expression and characterization of (E)-β farnesene synthase from Citrus junos. Biol. Pharm. Bull. 24 (2001) 1171–1175. [PMID: 11642326]
6.  Crock, J., Wildung, M. and Croteau, R. Isolation and bacterial expression of a sesquiterpene synthase cDNA clone from peppermint (Mentha × piperita, L.) that produces the aphid alarm pheromone (E)-β-farnesene. Proc. Natl. Acad. Sci. USA 94 (1997) 12833–12838. [DOI] [PMID: 9371761]
7.  Schnee, C., Kollner, T.G., Gershenzon, J. and Degenhardt, J. The maize gene terpene synthase 1 encodes a sesquiterpene synthase catalyzing the formation of (E)-β-farnesene, (E)-nerolidol, and (E,E)-farnesol after herbivore damage. Plant Physiol. 130 (2002) 2049–2060. [DOI] [PMID: 12481088]
8.  Huber, D.P.W., Philippe, R.N., Godard, K.-A., Sturrock, R.N. and Bohlmann, J. Characterization of four terpene synthase cDNAs from methyl jasmonate-induced Douglas-fir, Pseudotsuga menziesii. Phytochemistry 66 (2005) 1427–1439. [DOI] [PMID: 15921711]
[EC 4.2.3.47 created 2010]
 
 
EC 4.2.3.48     
Accepted name: (3S,6E)-nerolidol synthase
Reaction: (2E,6E)-farnesyl diphosphate + H2O = (3S,6E)-nerolidol + diphosphate
For diagram of acyclic sesquiterpenoid biosynthesis, click here
Glossary: (3S,6E)-nerolidol = (3R,6E)-3,7,11-trimethyldodeca-1,6,10-trien-3-ol
Other name(s): (E)-nerolidol synthase; nerolidol synthase; (3S)-(E)-nerolidol synthase; FaNES1
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(3S,6E)-nerolidol-forming]
Comments: The enzyme catalyses a step in the formation of (3E)-4,8-dimethylnona-1,3,7-triene, a key signal molecule in induced plant defense mediated by the attraction of enemies of herbivores [2]. Nerolidol is a naturally occurring sesquiterpene found in the essential oils of many types of plants.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Aharoni, A., Giri, A.P., Verstappen, F.W., Bertea, C.M., Sevenier, R., Sun, Z., Jongsma, M.A., Schwab, W. and Bouwmeester, H.J. Gain and loss of fruit flavor compounds produced by wild and cultivated strawberry species. Plant Cell 16 (2004) 3110–3131. [DOI] [PMID: 15522848]
2.  Bouwmeester, H.J., Verstappen, F.W., Posthumus, M.A. and Dicke, M. Spider mite-induced (3S)-(E)-nerolidol synthase activity in cucumber and lima bean. The first dedicated step in acyclic C11-homoterpene biosynthesis. Plant Physiol. 121 (1999) 173–180. [PMID: 10482672]
3.  Degenhardt, J. and Gershenzon, J. Demonstration and characterization of (E)-nerolidol synthase from maize: a herbivore-inducible terpene synthase participating in (3E)-4,8-dimethyl-1,3,7-nonatriene biosynthesis. Planta 210 (2000) 815–822. [DOI] [PMID: 10805454]
4.  Arimura, G., Garms, S., Maffei, M., Bossi, S., Schulze, B., Leitner, M., Mithofer, A. and Boland, W. Herbivore-induced terpenoid emission in Medicago truncatula: concerted action of jasmonate, ethylene and calcium signaling. Planta 227 (2008) 453–464. [DOI] [PMID: 17924138]
[EC 4.2.3.48 created 2010]
 
 
EC 4.2.3.49     
Accepted name: (3R,6E)-nerolidol synthase
Reaction: (2E,6E)-farnesyl diphosphate + H2O = (3R,6E)-nerolidol + diphosphate
For diagram of acyclic sesquiterpenoid biosynthesis, click here
Other name(s): terpene synthase 1
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(3R,6E)-nerolidol-forming]
Comments: The enzyme catalyses a step in the formation of (3E)-4,8-dimethylnona-1,3,7-triene, a key signal molecule in induced plant defense mediated by the attraction of enemies of herbivores [1]. Nerolidol is a naturally occurring sesquiterpene found in the essential oils of many types of plants.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Schnee, C., Kollner, T.G., Gershenzon, J. and Degenhardt, J. The maize gene terpene synthase 1 encodes a sesquiterpene synthase catalyzing the formation of (E)-β-farnesene, (E)-nerolidol, and (E,E)-farnesol after herbivore damage. Plant Physiol. 130 (2002) 2049–2060. [DOI] [PMID: 12481088]
[EC 4.2.3.49 created 2010]
 
 
EC 4.2.3.50     
Accepted name: (+)-α-santalene synthase [(2Z,6Z)-farnesyl diphosphate cyclizing]
Reaction: (2Z,6Z)-farnesyl diphosphate = (+)-α-santalene + diphosphate
For diagram of santalene and bergamotene biosynthesis, click here
Other name(s): SBS (ambiguous)
Systematic name: (2Z,6Z)-farnesyl diphosphate lyase [cyclizing; (+)-α-santalene-forming]
Comments: The enzyme synthesizes a mixture of sesquiterpenoids from (2Z,6Z)-farnesyl diphosphate. Following dephosphorylation of (2Z,6Z)-farnesyl diphosphate, the (2Z,6Z)-farnesyl carbocation is converted to either the (6R)- or the (6S)-bisabolyl cations depending on the stereochemistry of the 6,1 closure. The (6R)-bisabolyl cation will then lead to the formation of (+)-α-santalene (EC 4.2.3.50), while the (6S)-bisabolyl cation will give rise to (+)-endo-β-bergamotene (see EC 4.2.3.53) as well as (-)-endo-α-bergamotene (see EC 4.2.3.54). Small amounts of (-)-epi-β-santalene are also formed from the (6R)-bisabolyl cation and small amounts of (-)-exo-α-bergamotene are formed from the (6S)-bisabolyl cation [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Sallaud, C., Rontein, D., Onillon, S., Jabes, F., Duffe, P., Giacalone, C., Thoraval, S., Escoffier, C., Herbette, G., Leonhardt, N., Causse, M. and Tissier, A. A novel pathway for sesquiterpene biosynthesis from Z,Z-farnesyl pyrophosphate in the wild tomato Solanum habrochaites. Plant Cell 21 (2009) 301–317. [DOI] [PMID: 19155349]
[EC 4.2.3.50 created 2010]
 
 
EC 4.2.3.51     
Accepted name: β-phellandrene synthase (neryl-diphosphate-cyclizing)
Reaction: neryl diphosphate = β-phellandrene + diphosphate
Other name(s): phellandrene synthase 1; PHS1; monoterpene synthase PHS1
Systematic name: neryl-diphosphate diphosphate-lyase [cyclizing; β-phellandrene-forming]
Comments: The enzyme from Solanum lycopersicum has very poor affinity with geranyl diphosphate as substrate. Catalyses the formation of the acyclic myrcene and ocimene as major products in addition to β-phellandrene [1].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Schilmiller, A.L., Schauvinhold, I., Larson, M., Xu, R., Charbonneau, A.L., Schmidt, A., Wilkerson, C., Last, R.L. and Pichersky, E. Monoterpenes in the glandular trichomes of tomato are synthesized from a neryl diphosphate precursor rather than geranyl diphosphate. Proc. Natl. Acad. Sci. USA 106 (2009) 10865–10870. [DOI] [PMID: 19487664]
[EC 4.2.3.51 created 2010]
 
 
EC 4.2.3.52     
Accepted name: (4S)-β-phellandrene synthase (geranyl-diphosphate-cyclizing)
Reaction: geranyl diphosphate = (4S)-β-phellandrene + diphosphate
For diagram of menthane monoterpenoid biosynthesis, click here
Other name(s): phellandrene synthase; (-)-β-phellandrene synthase; (-)-(4S)-β-phellandrene synthase
Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing; (4S)-β-phellandrene-forming]
Comments: Requires Mn2+. Mg2+ is not effective [1]. Some (-)-α-phellandrene is also formed [3]. The reaction involves a 1,3-hydride shift [4].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 137010-34-5
References:
1.  Savage, T.J., Hatch, M.W. and Croteau, R. Monoterpene synthases of Pinus contorta and related conifers. A new class of terpenoid cyclase. J. Biol. Chem. 269 (1994) 4012–4020. [PMID: 8307957]
2.  Bohlmann, J., Phillips, M., Ramachandiran, V., Katoh, S. and Croteau, R. cDNA cloning, characterization, and functional expression of four new monoterpene synthase members of the Tpsd gene family from grand fir (Abies grandis). Arch. Biochem. Biophys. 368 (1999) 232–243. [DOI] [PMID: 10441373]
3.  Wagschal, K., Savage, T.J. and Croteau, R. Isotopically sensitive branching as a tool for evaluating multiple product formation by monoterpene cyclases. Tetrahedron 31 (1991) 5933–5944.
4.  LaFever, R.E. and Croteau, R. Hydride shifts in the biosynthesis of the p-menthane monoterpenes α-terpinene, γ-terpinene, and β-phellandrene. Arch. Biochem. Biophys. 301 (1993) 361–366. [DOI] [PMID: 8460944]
[EC 4.2.3.52 created 2010]
 
 
EC 4.2.3.53     
Accepted name: (+)-endo-β-bergamotene synthase [(2Z,6Z)-farnesyl diphosphate cyclizing]
Reaction: (2Z,6Z)-farnesyl diphosphate = (+)-endo-β-bergamotene + diphosphate
For diagram of santalene and bergamotene biosynthesis, click here
Other name(s): SBS (ambiguous)
Systematic name: (2Z,6Z)-farnesyl diphosphate lyase (cyclizing; (+)-endo-β-bergamotene-forming)
Comments: The enzyme synthesizes a mixture of sesquiterpenoids from (2Z,6Z)-farnesyl diphosphate. Following dephosphorylation of (2Z,6Z)-farnesyl diphosphate, the (2Z,6Z)-farnesyl carbocation is converted to either the (6R)- or the (6S)-bisabolyl cations depending on the stereochemistry of the 6,1 closure. The (6R)-bisabolyl cation will then lead to the formation of (+)-α-santalene (see EC 4.2.3.50), while the (6S)-bisabolyl cation will give rise to (-)-endo-α-bergamotene (see EC 4.2.3.54), as well as (+)-endo-β-bergamotene. Small amounts of (-)-epi-β-santalene are also formed from the (6R)-bisabolyl cation and small amounts of (-)-exo-α-bergamotene are formed from the (6S)-bisabolyl cation [1].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Sallaud, C., Rontein, D., Onillon, S., Jabes, F., Duffe, P., Giacalone, C., Thoraval, S., Escoffier, C., Herbette, G., Leonhardt, N., Causse, M. and Tissier, A. A novel pathway for sesquiterpene biosynthesis from Z,Z-farnesyl pyrophosphate in the wild tomato Solanum habrochaites. Plant Cell 21 (2009) 301–317. [DOI] [PMID: 19155349]
[EC 4.2.3.53 created 2010]
 
 
EC 4.2.3.54     
Accepted name: (-)-endo-α-bergamotene synthase [(2Z,6Z)-farnesyl diphosphate cyclizing]
Reaction: (2Z,6Z)-farnesyl diphosphate = (-)-endo-α-bergamotene + diphosphate
For diagram of santalene and bergamotene biosynthesis, click here
Other name(s): SBS (ambiguous)
Systematic name: (2Z,6Z)-farnesyl diphosphate lyase [cyclizing; (-)-endo-α-bergamotene-forming]
Comments: The enzyme synthesizes a mixture of sesquiterpenoids from (2Z,6Z)-farnesyl diphosphate. Following dephosphorylation of (2Z,6Z)-farnesyl diphosphate, the (2Z,6Z)-farnesyl carbocation is converted to either the (6R)- or the (6S)-bisabolyl cations depending on the stereochemistry of the 6,1 closure. The (6R)-bisabolyl cation will then lead to the formation of (+)-α-santalene (see EC 4.2.3.50), while the (6S)-bisabolyl cation will give rise to (+)-endo-β-bergamotene (EC 4.2.3.53) as well as (-)-endo-α-bergamotene. Small amounts of (-)-epi-β-santalene are also formed from the (6R)-bisabolyl cation and small amounts of (-)-exo-α-bergamotene are formed from the (6S)-bisabolyl cation [1].
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Sallaud, C., Rontein, D., Onillon, S., Jabes, F., Duffe, P., Giacalone, C., Thoraval, S., Escoffier, C., Herbette, G., Leonhardt, N., Causse, M. and Tissier, A. A novel pathway for sesquiterpene biosynthesis from Z,Z-farnesyl pyrophosphate in the wild tomato Solanum habrochaites. Plant Cell 21 (2009) 301–317. [DOI] [PMID: 19155349]
[EC 4.2.3.54 created 2010]
 
 
EC 4.2.3.55     
Accepted name: (S)-β-bisabolene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (S)-β-bisabolene + diphosphate
For diagram of bisabolene biosynthesis, click here, for diagram of bisabolene biosynthesis, click here and for diagram of bisabolene and macrocarpene biosynthesis, click here
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(S)-β-bisabolene-forming]
Comments: The synthesis of (S)-β-macrocarpene from (2E,6E)-farnesyl diphosphate proceeds in two steps. The first step is the cyclization to (S)-β-bisabolene. The second step is the isomerization to (S)-β-macrocarpene (cf. EC 5.5.1.17, (S)-β-macrocarpene synthase). The enzyme requires Mg2+ or Mn2+ for activity.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Fujisawa, M., Harada, H., Kenmoku, H., Mizutani, S. and Misawa, N. Cloning and characterization of a novel gene that encodes (S)-β-bisabolene synthase from ginger, Zingiber officinale. Planta 232 (2010) 121–130. [DOI] [PMID: 20229191]
[EC 4.2.3.55 created 2011]
 
 
EC 4.2.3.56     
Accepted name: γ-humulene synthase
Reaction: (2E,6E)-farnesyl diphosphate = γ-humulene + diphosphate
For diagram of humulene-based sequiterpenoid biosynthesis, click here
Other name(s): humulene cyclase
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (γ-humulene-forming)
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 110639-19-5
References:
1.  Steele, C.L., Crock, J., Bohlmann, J. and Croteau, R. Sesquiterpene synthases from grand fir (Abies grandis). Comparison of constitutive and wound-induced activities, and cDNA isolation, characterization, and bacterial expression of δ-selinene synthase and γ-humulene synthase. J. Biol. Chem. 273 (1998) 2078–2089. [DOI] [PMID: 9442047]
2.  Little, D.B. and Croteau, R.B. Alteration of product formation by directed mutagenesis and truncation of the multiple-product sesquiterpene synthases δ-selinene synthase and γ-humulene synthase. Arch. Biochem. Biophys. 402 (2002) 120–135. [DOI] [PMID: 12051690]
[EC 4.2.3.56 created 2011]
 
 
EC 4.2.3.57     
Accepted name: (-)-β-caryophyllene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (-)-β-caryophyllene + diphosphate
For diagram of humulene-based sequiterpenoid biosynthesis, click here
Other name(s): β-caryophyllene synthase; (2E,6E)-farnesyl-diphosphate diphosphate-lyase (caryophyllene-forming)
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(-)-β-caryophyllene-forming]
Comments: Widely distributed in higher plants, cf. EC 4.2.3.89 (+)-β-caryophyllene synthase.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 110639-18-4
References:
1.  Cai, Y., Jia, J.W., Crock, J., Lin, Z.X., Chen, X.Y. and Croteau, R. A cDNA clone for β-caryophyllene synthase from Artemisia annua. Phytochemistry 61 (2002) 523–529. [DOI] [PMID: 12409018]
[EC 4.2.3.57 created 2011, modified 2011]
 
 
EC 4.2.3.58     
Accepted name: longifolene synthase
Reaction: (2E,6E)-farnesyl diphosphate = longifolene + diphosphate
For diagram of humulene-based sequiterpenoid biosynthesis, click here, and for mechanism, click here
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (longifolene-forming)
Comments: As well as 61% longifolene the enzyme gives 15% of α-longipinene, 6% longicyclene and traces of other sesquiterpenoids.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Martin, D.M., Faldt, J. and Bohlmann, J. Functional characterization of nine Norway Spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily. Plant Physiol. 135 (2004) 1908–1927. [DOI] [PMID: 15310829]
[EC 4.2.3.58 created 2011]
 
 
EC 4.2.3.59     
Accepted name: (E)-γ-bisabolene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (E)-γ-bisabolene + diphosphate
For diagram of bisabolene biosynthesis, click here and for diagram of bisabolene biosynthesis, click here
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(E)-γ-bisabolene-forming]
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Huber, D.P.W., Philippe, R.N., Godard, K.-A., Sturrock, R.N. and Bohlmann, J. Characterization of four terpene synthase cDNAs from methyl jasmonate-induced Douglas-fir, Pseudotsuga menziesii. Phytochemistry 66 (2005) 1427–1439. [DOI] [PMID: 15921711]
[EC 4.2.3.59 created 2011]
 
 
EC 4.2.3.60     
Accepted name: germacrene C synthase
Reaction: (2E,6E)-farnesyl diphosphate = germacrene C + diphosphate
For diagram of germacrene-derived sesquiterpenoid biosynthesis, click here
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase (germacrene-C-forming)
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc
References:
1.  Colby, S.M., Crock, J., Dowdle-Rizzo, B., Lemaux, P.G. and Croteau, R. Germacrene C synthase from Lycopersicon esculentum cv. VFNT cherry tomato: cDNA isolation, characterization, and bacterial expression of the multiple product sesquiterpene cyclase. Proc. Natl. Acad. Sci. USA 95 (1998) 2216–2221. [DOI] [PMID: 9482865]
[EC 4.2.3.60 created 2011]
 
 
EC 4.2.3.61     
Accepted name: 5-epiaristolochene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (+)-5-epiaristolochene + diphosphate
For diagram of eremophilane and spirovetivane sesquiterpenoid biosynthesis, click here
Other name(s): 5-epi-aristolochene synthase; tobacco epiaristolochene synthase; farnesyl pyrophosphate cyclase (ambiguous); EAS; TEAS
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-5-epiaristolochene-forming]
Comments: Initial cyclization gives (+)-germacrene A in an enzyme bound form which is not released to the medium.
Links to other databases: BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB
References:
1.  Back, K., Yin, S. and Chappell, J. Expression of a plant sesquiterpene cyclase gene in Escherichia coli. Arch. Biochem. Biophys. 315 (1994) 527–532. [DOI] [PMID: 7986100]
2.  Starks, C.M., Back, K., Chappell, J. and Noel, J.P. Structural basis for cyclic terpene biosynthesis by tobacco 5-epi-aristolochene synthase. Science 277 (1997) 1815–1820. [DOI] [PMID: 9295271]
3.  Back, K., He, S., Kim, K.U. and Shin, D.H. Cloning and bacterial expression of sesquiterpene cyclase, a key branch point enzyme for the synthesis of sesquiterpenoid phytoalexin capsidiol in UV-challenged leaves of Capsicum annuum. Plant Cell Physiol. 39 (1998) 899–904. [PMID: 9816674]
4.  Rising, K.A., Starks, C.M., Noel, J.P. and Chappell, J. Demonstration of germacrene A as an intermediate in 5-epi-aristolochene synthase catalysis. J. Am. Chem. Soc. 122 (2000) 1861–1866.
5.  Bohlmann, J., Stauber, E.J., Krock, B., Oldham, N.J., Gershenzon, J. and Baldwin, I.T. Gene expression of 5-epi-aristolochene synthase and formation of capsidiol in roots of Nicotiana attenuata and N. sylvestris. Phytochemistry 60 (2002) 109–116. [DOI] [PMID: 12009313]
6.  O'Maille, P.E., Chappell, J. and Noel, J.P. Biosynthetic potential of sesquiterpene synthases: alternative products of tobacco 5-epi-aristolochene synthase. Arch. Biochem. Biophys. 448 (2006) 73–82. [DOI] [PMID: 16375847]
[EC 4.2.3.61 created 2011]
 
 


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