EC |
4.2.3.18 |
Accepted name: |
abieta-7,13-diene synthase |
Reaction: |
(+)-copalyl diphosphate = abieta-7,13-diene + diphosphate |
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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] |
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[EC 4.2.3.18 created 2002, modified 2012] |
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EC |
4.2.3.32 |
Accepted name: |
levopimaradiene synthase |
Reaction: |
(+)-copalyl diphosphate = abieta-8(14),12-diene + diphosphate |
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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] |
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[EC 4.2.3.32 created 2008, modified 2012] |
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EC |
4.2.3.44 |
Accepted name: |
isopimara-7,15-diene synthase |
Reaction: |
(+)-copalyl diphosphate = isopimara-7,15-diene + diphosphate |
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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] |
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[EC 4.2.3.44 created 2009] |
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EC |
4.2.3.45 |
Accepted name: |
phyllocladan-16α-ol synthase |
Reaction: |
(+)-copalyl diphosphate + H2O = phyllocladan-16α-ol + diphosphate |
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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] |
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[EC 4.2.3.45 created 2009] |
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EC |
4.2.3.131 |
Accepted name: |
miltiradiene synthase |
Reaction: |
(+)-copalyl diphosphate = miltiradiene + diphosphate |
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For diagram of abietane diterpenoids biosynthesis, click here |
Other name(s): |
SmMDS; SmiKSL; RoKSL |
Systematic name: |
(+)-copalyl-diphosphate diphosphate-lyase (cyclizing, miltiradiene-forming) |
Comments: |
Isolated from the plants Rosmarinus officinalis (rosemary) and Salvia miltiorrhiza. The enzyme from the plant Selaginella moellendorffii is mutifunctional and also catalyses EC 5.5.1.12, copalyl diphosphate synthase [2]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Gao, W., Hillwig, M.L., Huang, L., Cui, G., Wang, X., Kong, J., Yang, B. and Peters, R.J. A functional genomics approach to tanshinone biosynthesis provides stereochemical insights. Org. Lett. 11 (2009) 5170–5173. [DOI] [PMID: 19905026] |
2. |
Sugai, Y., Ueno, Y., Hayashi, K., Oogami, S., Toyomasu, T., Matsumoto, S., Natsume, M., Nozaki, H. and Kawaide, H. Enzymatic 13C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii. J. Biol. Chem. 286 (2011) 42840–42847. [DOI] [PMID: 22027823] |
3. |
Bruckner, K., Bozic, D., Manzano, D., Papaefthimiou, D., Pateraki, I., Scheler, U., Ferrer, A., de Vos, R.C., Kanellis, A.K. and Tissier, A. Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes. Phytochemistry 101 (2014) 52–64. [DOI] [PMID: 24569175] |
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[EC 4.2.3.131 created 2012] |
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EC |
4.2.3.132 |
Accepted name: |
neoabietadiene synthase |
Reaction: |
(+)-copalyl diphosphate = neoabietadiene + diphosphate |
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For diagram of abietane diterpenoids biosynthesis, click here |
Glossary: |
neoabietadiene = abieta-8(14),13(15)-diene |
Other name(s): |
TPS-LAS |
Systematic name: |
(+)-copaly-diphosphate diphosphate-lyase (cyclizing, neoabietadiene-forming) |
Comments: |
Isolated from Abies grandis (grand fir) [1]. This class I enzyme forms about equal proportions of abietadiene, levopimaradiene and neoabietadiene. See also EC 4.2.3.18, abieta-7,13-diene synthase and EC 4.2.3.32, levopimaradiene synthase. An X-ray study of this multifunctional enzyme showed that the class I activity is in the α domain, while (+)-copalyl diphosphate synthase activity (EC 5.5.1.12, a class II activity) is in the β and γ domains [2]. In Pinus taeda (loblolly pine) the major product is levopimaradiene, with less abietadiene and neoabietadiene [3]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
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. |
Zhou, K., Gao, Y., Hoy, J.A., Mann, F.M., Honzatko, R.B. and Peters, R.J. Insights into diterpene cyclization from structure of bifunctional abietadiene synthase from Abies grandis. J. Biol. Chem. 287 (2012) 6840–6850. [DOI] [PMID: 22219188] |
3. |
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] |
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[EC 4.2.3.132 created 2012] |
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EC |
4.2.3.147 |
Accepted name: |
pimaradiene synthase |
Reaction: |
(+)-copalyl diphosphate = pimara-8(14),15-diene + diphosphate |
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For diagram of pimarane diterpenoids biosynthesis, click here |
Other name(s): |
PbmPIM1; PcmPIM1 |
Systematic name: |
(+)-copalyl diphosphate-lyase (pimara-8(14),15-diene-forming) |
Comments: |
Isolated from the plants Pinus banksiana (jack pine) and Pinus contorta (lodgepole pine). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Hall, D.E., Zerbe, P., Jancsik, S., Quesada, A.L., Dullat, H., Madilao, L.L., Yuen, M. and Bohlmann, J. Evolution of conifer diterpene synthases: diterpene resin acid biosynthesis in lodgepole pine and jack pine involves monofunctional and bifunctional diterpene synthases. Plant Physiol. 161 (2013) 600–616. [DOI] [PMID: 23370714] |
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[EC 4.2.3.147 created 2014] |
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EC |
4.2.3.183 |
Accepted name: |
nezukol synthase |
Reaction: |
(+)-copalyl diphosphate + H2O = nezukol + diphosphate |
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For diagram of pimarane diterpenoids biosynthesis, 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
nezukol = pimar-15-en-8-ol
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Other name(s): |
TPS2 |
Systematic name: |
(+)-copalyl-diphosphate diphosphate-lyase (cyclizing, nezukol-forming) |
Comments: |
Isolated from the plant Isodon rubescens. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc |
References: |
1. |
Pelot, K.A., Hagelthorn, D.M., Addison, J.B. and Zerbe, P. Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases. PLoS One 12:e0176507 (2017). [DOI] [PMID: 28445526] |
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[EC 4.2.3.183 created 2017] |
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EC |
4.2.3.193 |
Accepted name: |
(12E)-labda-8(17),12,14-triene synthase |
Reaction: |
(+)-copalyl diphosphate = (12E)-labda-8(17),12,14-triene + diphosphate |
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For diagram of pimarane diterpenoids biosynthesis, click here |
Other name(s): |
CldD |
Systematic name: |
(+)-copalyl-diphosphate diphosphate-lyase [(12E)-labda-8(17),12,14-triene-forming] |
Comments: |
Isolated from the bacterium Streptomyces cyslabdanicus. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Yamada, Y., Komatsu, M. and Ikeda, H. Chemical diversity of labdane-type bicyclic diterpene biosynthesis in Actinomycetales microorganisms. J. Antibiot. (Tokyo) 69 (2016) 515–523. [DOI] [PMID: 26814669] |
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[EC 4.2.3.193 created 2017] |
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EC |
5.5.1.12 |
Accepted name: |
copalyl diphosphate synthase |
Reaction: |
geranylgeranyl diphosphate = (+)-copalyl diphosphate |
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For diagram of abietadiene, abietate, isopimaradiene, labdadienol and sclareol biosynthesis, click here, for diagram of labdane diterpenoids biosynthesis, click here and for diagram of pimarane diterpenoids biosynthesis, click here |
Other name(s): |
(+)-copalyl-diphosphate lyase (decyclizing) |
Systematic name: |
(+)-copalyl-diphosphate lyase (ring-opening) |
Comments: |
In some plants, such as Salvia miltiorrhiza, this enzyme is monofunctional. In other plants this activity is often a part of a bifunctional enzyme. For example, in Selaginella moellendorffii this activity is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.131, miltiradiene synthase, while in the tree Abies grandis (grand fir) it is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.18, abietadiene synthase. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 157972-08-2 |
References: |
1. |
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] |
2. |
Sugai, Y., Ueno, Y., Hayashi, K., Oogami, S., Toyomasu, T., Matsumoto, S., Natsume, M., Nozaki, H. and Kawaide, H. Enzymatic 13C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii. J. Biol. Chem. 286 (2011) 42840–42847. [DOI] [PMID: 22027823] |
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. |
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] |
5. |
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] |
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[EC 5.5.1.12 created 2002, modified 2012] |
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