ExplorEnz: EC 4.*

References:

1.	Nabeta, K., Fujita, M., Komuro, K., Katayama, K., and Takasawa, T. In vitro biosynthesis of cadinanes by cell-free extracts of cultured cells of Heteroscyphus planus. J. Chem. Soc., Perkin Trans. 1 (1997) 2065–2070.

[EC 4.2.3.62 created 2011, modified 2011]

4.2.3.63

Accepted name:

(+)-cubenene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-cubenene + diphosphate

For diagram of ent-cadinane sesquiterpenoid biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-cubenene-forming]

Comments:

Requires Mg²⁺.

Links to other databases:

References:

1.	Nabeta, K., Kigure, K., Fujita, M., Nagoya, T., Ishikawa, T., Okuyama, H. and Takasawa, T. Bioynthesis of (+)-cubenene and (+)-epicubenol by cell-free extracts of cultured cells of Heteroscyphus planus and cyclization of [²H]farnesyl diphosphates. J. Chem. Soc., Perkin Trans. 1 (1995) 1935–1939.
2.	Nabeta, K., Fujita, M., Komuro, K., Katayama, K., and Takasawa, T. In vitro biosynthesis of cadinanes by cell-free extracts of cultured cells of Heteroscyphus planus. J. Chem. Soc., Perkin Trans. 1 (1997) 2065–2070.

[EC 4.2.3.63 created 2011]

4.2.3.64

Accepted name:

(+)-epicubenol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = (+)-epicubenol + diphosphate

For diagram of ent-cadinane sesquiterpenoid biosynthesis, click here

Other name(s):

farnesyl pyrophosphate cyclase (ambiguous)

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-epicubenol-forming]

Comments:

Requires Mg²⁺. In the bacteria Streptomyces and the liverwort Heteroscyphus the (+)-isomer is formed in contrast to higher plants where the (-)-isomer is formed.

Links to other databases:

References:

1.	Cane, D.E., Tandon, M., and Prabhakaran, P.C. Epicubenol synthase and the enzymatic cyclization of farnesyl diphosphate. J. Am. Chem. Soc. 115 (1993) 8103–8106.
2.	Cane, D.E. and Tandon, M. Biosynthesis of (+)-epicubenol. Tetrahedron Lett. 35 (1994) 5355–5358.
3.	Cane, D.E. and Tandon, M. Epicubenol synthase and the stereochemistry of the enzymatic cyclization of farnesyl and nerolidyl diphosphate. J. Am. Chem. Soc. 117 (1995) 5602–5603.
4.	Nabeta, K., Kigure, K., Fujita, M., Nagoya, T., Ishikawa, T., Okuyama, H. and Takasawa, T. Bioynthesis of (+)-cubenene and (+)-epicubenol by cell-free extracts of cultured cells of Heteroscyphus planus and cyclization of [²H]farnesyl diphosphates. J. Chem. Soc., Perkin Trans. 1 (1995) 1935–1939.
5.	Nabeta, K., Fujita, M., Komuro, K., Katayama, K., and Takasawa, T. In vitro biosynthesis of cadinanes by cell-free extracts of cultured cells of Heteroscyphus planus. J. Chem. Soc., Perkin Trans. 1 (1997) 2065–2070.

[EC 4.2.3.64 created 2011]

4.2.3.65

Accepted name:

zingiberene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = zingiberene + diphosphate

For diagram of bisabolene biosynthesis, click here, for diagram of bisabolene biosynthesis, click here and for diagram of γ-curcumene, β-sesquiphellandrene and zingiberene biosynthesis, click here

Other name(s):

α-zingiberene synthase; ZIS

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (zingiberene-forming)

Links to other databases:

References:

1.	Davidovich-Rikanati, R., Lewinsohn, E., Bar, E., Iijima, Y., Pichersky, E. and Sitrit, Y. Overexpression of the lemon basil α-zingiberene synthase gene increases both mono- and sesquiterpene contents in tomato fruit. Plant J. 56 (2008) 228–238. [DOI] [PMID: 18643974]

[EC 4.2.3.65 created 2011]

4.2.3.66

Accepted name:

β-selinene cyclase

Reaction:

(2E,6E)-farnesyl diphosphate = β-selinene + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (β-selinene-forming)

Comments:

Initial cyclization gives (+)-germacrene A in an enzyme bound form which is not released to the medium.

Links to other databases:

References:

1.	Belingher, L., Cartayrade, A., Pauly, G. and Gleizes, M. Partial purification and properties of the sesquiterpene β-selinene cyclase from Citrofortunella mitis. Plant Sci. 84 (1992) 129–136.

[EC 4.2.3.66 created 2011]

4.2.3.67

Accepted name:

cis-muuroladiene synthase

Reaction:

(1) (2E,6E)-farnesyl diphosphate = cis-muurola-3,5-diene + diphosphate
(2) (2E,6E)-farnesyl diphosphate = cis-muurola-4(14),5-diene + diphosphate

For diagram of cadinane sesquiterpenoid biosynthesis, click here and for diagram of cadinene, cubebol and muuroladiene biosynthesis, click here

Other name(s):

MxpSS1

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cis-muuroladiene-forming)

Comments:

The recombinant enzyme from black peppermint (Mentha x piperita) gave a mixture of cis-muurola-3,5-diene (45%) and cis-muurola-4(14),5-diene (43%).

Links to other databases:

References:

Prosser, I.M., Adams, R.J., Beale, M.H., Hawkins, N.D., Phillips, A.L., Pickett, J.A. and Field, L.M. Cloning and functional characterisation of a cis-muuroladiene synthase from black peppermint (Mentha × piperita) and direct evidence for a chemotype unable to synthesise farnesene. Phytochemistry 67 (2006) 1564–1571. [DOI] [PMID: 16083926]

[EC 4.2.3.67 created 2011]

4.2.3.68

Accepted name:

β-eudesmol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = β-eudesmol + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here and for diagram of eudesmol biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (β-eudesmol-forming)

Comments:

The recombinant enzyme from ginger (Zingiber zerumbet) gives 62.6% β-eudesmol, 16.8% 10-epi-γ-eudesmol (cf. EC 4.2.3.84, 10-epi-γ-eudesmol synthase), 10% α-eudesmol (cf. EC 4.2.3.85, α-eudesmol synthase), and 5.6% aristolene.

Links to other databases:

References:

1.	Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565–572. [DOI] [PMID: 18242187]

[EC 4.2.3.68 created 2011, modified 2011, modified 2012]

4.2.3.69

Accepted name:

(+)-α-barbatene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-α-barbatene + diphosphate

For diagram of barbatene biosynthesis, click here and for diagram of biosynthesis of tricyclic sesquiterpenoids derived from bisabolyl cation, click here

Other name(s):

AtBS

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-α-barbatene-forming]

Comments:

The recombinant enzyme from the plant Arabidopsis thaliana produces 27.3% α-barbatene, 17.8% thujopsene (cf. EC 4.2.3.79, thujopsene synthase) and 9.9% β-chamigrene (cf. EC 4.2.3.78, β-chamigrene synthase) [1] plus traces of other sesquiterpenoids [2].

Links to other databases:

References:

1.	Wu, S., Schoenbeck, M.A., Greenhagen, B.T., Takahashi, S., Lee, S., Coates, R.M. and Chappell, J. Surrogate splicing for functional analysis of sesquiterpene synthase genes. Plant Physiol. 138 (2005) 1322–1333. [DOI] [PMID: 15965019]
2.	Tholl, D., Chen, F., Petri, J., Gershenzon, J. and Pichersky, E. Two sesquiterpene synthases are responsible for the complex mixture of sesquiterpenes emitted from Arabidopsis flowers. Plant J. 42 (2005) 757–771. [DOI] [PMID: 15918888]

[EC 4.2.3.69 created 2011, modified 2012]

4.2.3.70

Accepted name:

patchoulol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = patchoulol + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (patchoulol-forming)

Links to other databases:

References:

1.	Croteau, R., Munck, S.L., Akoh, C.C., Fisk, H.J. and Satterwhite, D.M. Biosynthesis of the sesquiterpene patchoulol from farnesyl pyrophosphate in leaf extracts of Pogostemon cablin (patchouli): mechanistic considerations. Arch. Biochem. Biophys. 256 (1987) 56–68. [DOI] [PMID: 3038029]
2.	Munck, S.L. and Croteau, R. Purification and characterization of the sesquiterpene cyclase patchoulol synthase from Pogostemon cablin. Arch. Biochem. Biophys. 282 (1990) 58–64. [DOI] [PMID: 2171435]
3.	Faraldos, J.A., Wu, S., Chappell, J. and Coates, R.M. Doubly deuterium-labeled patchouli alcohol from cyclization of singly labeled [2-²H₁]farnesyl diphosphate catalyzed by recombinant patchoulol synthase. J. Am. Chem. Soc. 132 (2010) 2998–3008. [DOI] [PMID: 20148554]

[EC 4.2.3.70 created 2011]

4.2.3.71

Accepted name:

(E,E)-germacrene B synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (E,E)-germacrene B + diphosphate

For diagram of germacrene-derived sesquiterpenoid biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(E,E)-germacrene-B-forming]

Links to other databases:

References:

1.	van Der Hoeven, R.S., Monforte, A.J., Breeden, D., Tanksley, S.D. and Steffens, J.C. Genetic control and evolution of sesquiterpene biosynthesis in Lycopersicon esculentum and L. hirsutum. Plant Cell 12 (2000) 2283–2294. [PMID: 11090225]

[EC 4.2.3.71 created 2011]

4.2.3.72

Accepted name:

α-gurjunene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-α-gurjunene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(-)-α-gurjunene-forming]

Comments:

Initial cyclization probably gives biyclogermacrene in an enzyme bound form which is not released to the medium. The enzyme from Solidago canadensis also forms a small amount of (+)-γ-gurjunene [1].

Links to other databases:

References:

1.	Schmidt, C.O., Bouwmeester, H.J., Bulow, N. and Konig, W.A. Isolation, characterization, and mechanistic studies of (-)-α-gurjunene synthase from Solidago canadensis. Arch. Biochem. Biophys. 364 (1999) 167–177. [DOI] [PMID: 10190971]

[EC 4.2.3.72 created 2011]

4.2.3.73

Accepted name:

valencene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-valencene + diphosphate

For diagram of eremophilane and spirovetivane sesquiterpenoid biosynthesis, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (valencene-forming)

Comments:

The recombinant enzyme from Vitis vinifera gave 49.5% (+)-valencene and 35.5% (-)-7-epi-α-selinene. Initial cyclization gives (+)-germacrene A in an enzyme bound form which is not released to the medium.

Links to other databases:

References:

Lucker, J., Bowen, P. and Bohlmann, J. Vitis vinifera terpenoid cyclases: functional identification of two sesquiterpene synthase cDNAs encoding (+)-valencene synthase and (-)-germacrene D synthase and expression of mono- and sesquiterpene synthases in grapevine flowers and berries. Phytochemistry 65 (2004) 2649–2659. [DOI] [PMID: 15464152]

[EC 4.2.3.73 created 2011]

4.2.3.74

Accepted name:

presilphiperfolanol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = presilphiperfolan-8β-ol + diphosphate

For diagram of bicyclic and tricyclic sesquiterpenoids derived from humuladienyl cation, click here and for diagram of mechanism, click here

Other name(s):

BcBOT2; CND15

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphohydrolase (presilphiperfolan-8β-ol-forming)

Comments:

Requires Mg²⁺. Presilphiperfolan-8β-ol is the precursor of botrydial, a phytotoxic sesquiterpene metabolite secreted by the fungus Botryotinia fuckeliana (Botrytis cinerea), the causal agent of gray mold disease in plants.

Links to other databases:

References:

1.	Pinedo, C., Wang, C.M., Pradier, J.M., Dalmais, B., Choquer, M., Le Pecheur, P., Morgant, G., Collado, I.G., Cane, D.E. and Viaud, M. Sesquiterpene synthase from the botrydial biosynthetic gene cluster of the phytopathogen Botrytis cinerea. ACS Chem. Biol. 3 (2008) 791–801. [DOI] [PMID: 19035644]
2.	Wang, C.M., Hopson, R., Lin, X. and Cane, D.E. Biosynthesis of the sesquiterpene botrydial in Botrytis cinerea. Mechanism and stereochemistry of the enzymatic formation of presilphiperfolan-8β-ol. J. Am. Chem. Soc. 131 (2009) 8360–8361. [DOI] [PMID: 19476353]

[EC 4.2.3.74 created 2011]

4.2.3.75

Accepted name:

(-)-germacrene D synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-germacrene D + diphosphate

For diagram of gurjunene, patchoulol and selinene biosynthesis, click here

Glossary:

(-)-germacrene D = (1E,6E,8S)-1-methyl-5-methylidene-8-(propan-2-yl)cyclodeca-1,6-diene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(-)-germacrene-D-forming]

Comments:

In Solidago canadensis the biosynthesis results in the pro-R hydrogen at C-1 of the farnesy diphosphate ending up at C-11 of the (-)-germacrene D [1]. With Streptomyces coelicolor the pro-S hydrogen at C-1 ends up at C-11 of the (-)-germacrene D [2].

Links to other databases:

References:

1.	Schmidt, C.O., Bouwmeester, H.J., Franke, S. and König, W.A. Mechanisms of the biosynthesis of sesquiterpene enantiomers (+)- and (-)-germacrene D in Solidago canadensis. Chirality 11 (1999) 353–362.
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.	Lucker, J., Bowen, P. and Bohlmann, J. Vitis vinifera terpenoid cyclases: functional identification of two sesquiterpene synthase cDNAs encoding (+)-valencene synthase and (-)-germacrene D synthase and expression of mono- and sesquiterpene synthases in grapevine flowers and berries. Phytochemistry 65 (2004) 2649–2659. [DOI] [PMID: 15464152]
4.	Prosser, I., Altug, I.G., Phillips, A.L., Konig, W.A., Bouwmeester, H.J. and Beale, M.H. Enantiospecific (+)- and (-)-germacrene D synthases, cloned from goldenrod, reveal a functionally active variant of the universal isoprenoid-biosynthesis aspartate-rich motif. Arch. Biochem. Biophys. 432 (2004) 136–144. [DOI] [PMID: 15542052]

[EC 4.2.3.75 created 2011]

4.2.3.76

Accepted name:

(+)-δ-selinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-δ-selinene + diphosphate

For diagram of gurjunene, patchoulol and selinene biosynthesis, click here

Glossary:

(+)-δ-selinene = (4aR)-1,4a-dimethyl-7-(propan-2-yl)-2,3,4,4a,5,6-hexahydronaphthalene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-δ-selinene-forming]

Comments:

Initial cyclization gives germacrene C in an enzyme bound form which is not released to the medium.

Links to other databases:

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 4.2.3.76 created 2011]

4.2.3.77

Accepted name:

(+)-germacrene D synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-germacrene D + diphosphate

For diagram of germacrene sesquiterpenoid biosynthesis, click here

Glossary:

(+)-germacrene D = (1E,6E,8R)-1-methyl-5-methylidene-8-(propan-2-yl)cyclodeca-1,6-diene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase [(+)-germacrene-D-forming]

Comments:

Requires Mg²⁺, Mn²⁺, Ni²⁺ or Co²⁺. The formation of (+)-germacrene D involves a 1,2-hydride shift whereas for (-)-germacrene D there is a 1,3-hydride shift (see EC 4.2.3.75).

Links to other databases:

References:

1.	Picaud, S., Olsson, M.E., Brodelius, M. and Brodelius, P.E. Cloning, expression, purification and characterization of recombinant (+)-germacrene D synthase from Zingiber officinale. Arch. Biochem. Biophys. 452 (2006) 17–28. [DOI] [PMID: 16839518]

[EC 4.2.3.77 created 2011]

4.2.3.78

Accepted name:

β-chamigrene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-β-chamigrene + diphosphate

For diagram, click here

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (+)-β-chamigrene-forming)

Comments:

The recombinant enzyme from the plant Arabidopsis thaliana produces 27.3% (+)-α-barbatene, 17.8% (+)-thujopsene and 9.9% (+)-β-chamigrene [1] plus traces of other sesquiterpenoids [2]. See EC 4.2.3.69 (+)-α-barbatene synthase, and EC 4.2.3.79 thujopsene synthase.

Links to other databases:

References:

1.	Wu, S., Schoenbeck, M.A., Greenhagen, B.T., Takahashi, S., Lee, S., Coates, R.M. and Chappell, J. Surrogate splicing for functional analysis of sesquiterpene synthase genes. Plant Physiol. 138 (2005) 1322–1333. [DOI] [PMID: 15965019]
2.	Tholl, D., Chen, F., Petri, J., Gershenzon, J. and Pichersky, E. Two sesquiterpene synthases are responsible for the complex mixture of sesquiterpenes emitted from Arabidopsis flowers. Plant J. 42 (2005) 757–771. [DOI] [PMID: 15918888]

[EC 4.2.3.78 created 2011]

4.2.3.79

Accepted name:

thujopsene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-thujopsene + diphosphate

For diagram, click here

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (+)-thujopsene-forming)

Comments:

Links to other databases:

References:

1.	Wu, S., Schoenbeck, M.A., Greenhagen, B.T., Takahashi, S., Lee, S., Coates, R.M. and Chappell, J. Surrogate splicing for functional analysis of sesquiterpene synthase genes. Plant Physiol. 138 (2005) 1322–1333. [DOI] [PMID: 15965019]
2.	Tholl, D., Chen, F., Petri, J., Gershenzon, J. and Pichersky, E. Two sesquiterpene synthases are responsible for the complex mixture of sesquiterpenes emitted from Arabidopsis flowers. Plant J. 42 (2005) 757–771. [DOI] [PMID: 15918888]

[EC 4.2.3.79 created 2011]

4.2.3.80

Accepted name:

α-longipinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = α-longipinene + diphosphate

For diagram of humulene-based sequiterpenoid biosynthesis, click here and for mechanism, click here

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-longipinene-forming)

Comments:

The enzyme from Norway spruce produces longifolene as the main product (cf. EC 4.2.3.58, longifolene synthase). α-Longipinene constitutes about 15% of the total products.

Links to other databases:

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]
2.	Köpke, D., Schröder, R., Fischer, H.M., Gershenzon, J., Hilker, M. and Schmidt, A. Does egg deposition by herbivorous pine sawflies affect transcription of sesquiterpene synthases in pine? Planta 228 (2008) 427–438. [DOI] [PMID: 18493792]

[EC 4.2.3.80 created 2011]

4.2.3.81

Accepted name:

exo-α-bergamotene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-exo-α-bergamotene + diphosphate

For diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(-)-exo-α-bergamotene = (-)-trans-α-bergamotene = (1S,5S,6R)-2,6-dimethyl-6-(4-methylpent-3-en-1-yl)bicyclo[3.1.1]hept-2-ene

Other name(s):

trans-α-bergamotene synthase; LaBERS (gene name)

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (-)-exo-α-bergamotene-forming)

Comments:

The enzyme synthesizes a mixture of sesquiterpenoids from (2E,6E)-farnesyl diphosphate. As well as (-)-exo-α-bergamotene (74%) there were (E)-nerolidol (10%), (Z)-α-bisabolene (6%), (E)-β-farnesene (5%) and β-sesquiphellandrene (1%).

Links to other databases:

References:

1.	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]
2.	Landmann, C., Fink, B., Festner, M., Dregus, M., Engel, K.H. and Schwab, W. Cloning and functional characterization of three terpene synthases from lavender (Lavandula angustifolia). Arch. Biochem. Biophys. 465 (2007) 417–429. [DOI] [PMID: 17662687]

[EC 4.2.3.81 created 2011]

4.2.3.82

Accepted name:

α-santalene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-α-santalene + diphosphate

For diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(-)-exo-α-bergamotene = (-)-trans-α-bergamotene = (1S,5S,6R)-2,6-dimethyl-6-(4-methylpent-3-en-1-yl)bicyclo[3.1.1]hept-2-ene

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (+)-α-santalene-forming)

Comments:

The enzyme synthesizes a mixture of sesquiterpenoids from (2E,6E)-farnesyl diphosphate. As well as (+)-α-santalene, (-)-β-santalene and (-)-exo-α-bergamotene are formed with traces of (+)-epi-β-santalene. See EC 4.2.3.83 [(-)-β-santalene synthase], and EC 4.2.3.81 [(-)-exo-α-bergamotene synthase]. cf. EC 4.2.3.50 α-santalene synthase [(2Z,6Z)-farnesyl diphosphate cyclizing]

Links to other databases:

References:

Jones, C.G., Moniodis, J., Zulak, K.G., Scaffidi, A., Plummer, J.A., Ghisalberti, E.L., Barbour, E.L. and Bohlmann, J. Sandalwood fragrance biosynthesis involves sesquiterpene synthases of both the terpene synthase (TPS)-a and TPS-b subfamilies, including santalene synthases. J. Biol. Chem. 286 (2011) 17445–17454. [DOI] [PMID: 21454632]

[EC 4.2.3.82 created 2011]

4.2.3.83

Accepted name:

β-santalene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-β-santalene + diphosphate

For diagram of santalene and bergamotene biosynthesis, click here

Glossary:

(-)-exo-α-bergamotene = (-)-trans-α-bergamotene = (1S,5S,6R)-2,6-dimethyl-6-(4-methylpent-3-en-1-yl)bicyclo[3.1.1]hept-2-ene

Systematic name:

(2E,6E)-farnesyl diphosphate lyase (cyclizing, (-)-β-santalene-forming)

Comments:

The enzyme synthesizes a mixture of sesquiterpenoids from (2E,6E)-farnesyl diphosphate. As well as (-)-β-santalene (+)-α-santalene and (-)-exo-α-bergamotene are formed with traces of (+)-epi-β-santalene. See EC 4.2.3.82 [(+)-α-santalene synthase], and EC 4.2.3.81 [(-)-exo-α-bergamotene synthase].

Links to other databases:

References:

[EC 4.2.3.83 created 2011]

4.2.3.84

Accepted name:

10-epi-γ-eudesmol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = 10-epi-γ-eudesmol + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here and for diagram of eudesmol biosynthesis, click here

Glossary:

10-epi-γ-eudesmol = 2-[(2R,4aS)-4a,8-dimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-yl]propan-2-ol

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (10-epi-γ-eudesmol-forming)

Comments:

The recombinant enzyme from ginger (Zingiber zerumbet) gives 62.6% β-eudesmol, 16.8% 10-epi-γ-eudesmol, 10% α-eudesmol, and 5.6% aristolene. cf. EC 4.2.3.68 (β-eudesmol synthase) and EC 4.2.3.85 (α-eudesmol synthase)

Links to other databases:

References:

1.	Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565–572. [DOI] [PMID: 18242187]

[EC 4.2.3.84 created 2011]

4.2.3.85

Accepted name:

α-eudesmol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = α-eudesmol + diphosphate

For diagram of eudesmol biosynthesis, click here

Glossary:

(-)-α-eudesmol = 2-[(2R,4aR,8aR)-4a,8-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalen-2-yl]propan-2-ol

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-eudesmol-forming)

Comments:

Links to other databases:

References:

1.	Yu, F., Harada, H., Yamasaki, K., Okamoto, S., Hirase, S., Tanaka, Y., Misawa, N. and Utsumi, R. Isolation and functional characterization of a β-eudesmol synthase, a new sesquiterpene synthase from Zingiber zerumbet Smith. FEBS Lett. 582 (2008) 565–572. [DOI] [PMID: 18242187]

[EC 4.2.3.85 created 2011]

4.2.3.86

Accepted name:

7-epi-α-selinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = 7-epi-α-selinene + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here

Glossary:

7-epi-α-selinene = (2S,4aR,8aR)-4a,8-dimethyl-2-(prop-1-en-2-yl)-1,2,3,4,4a,5,6,8a-octahydronaphthalene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (7-epi-α-selinene-forming)

Comments:

The recombinant enzyme from Vitis vinifera forms 49.5% (+)-valencene (cf. EC 4.2.3.73, valencene synthase) and 35.5% (-)-7-epi-α-selinene. Initial cyclization gives (+)-germacrene A in an enzyme bound form which is not released to the medium.

Links to other databases:

References:

1.	Lucker, J., Bowen, P. and Bohlmann, J. Vitis vinifera terpenoid cyclases: functional identification of two sesquiterpene synthase cDNAs encoding (+)-valencene synthase and (-)-germacrene D synthase and expression of mono- and sesquiterpene synthases in grapevine flowers and berries. Phytochemistry 65 (2004) 2649–2659. [DOI] [PMID: 15464152]
2.	Martin, D.M., Toub, O., Chiang, A., Lo, B.C., Ohse, S., Lund, S.T. and Bohlmann, J. The bouquet of grapevine (Vitis vinifera L. cv. Cabernet Sauvignon) flowers arises from the biosynthesis of sesquiterpene volatiles in pollen grains. Proc. Natl. Acad. Sci. USA 106 (2009) 7245–7250. [DOI] [PMID: 19359488]

[EC 4.2.3.86 created 2011]

4.2.3.87

Accepted name:

α-guaiene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = α-guaiene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Other name(s):

PatTps177 (gene name)

Systematic name:

(2Z,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, α-guaiene-forming)

Comments:

Requires Mg²⁺. The enzyme from Pogostemon cablin gives 13% α-guaiene as well as 37% (-)-patchoulol (see EC 4.2.3.70), 13% δ-guaiene (see EC 4.2.3.93), and traces of at least ten other sesquiterpenoids [1]. In Aquilaria crassna three clones of the enzyme gave about 80% δ-guaiene and 20% α-guaiene, with traces of α-humulene. A fourth clone gave 54% δ-guaiene and 45% α-guaiene [2].

Links to other databases:

References:

1.	Deguerry, F., Pastore, L., Wu, S., Clark, A., Chappell, J. and Schalk, M. The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated with a limited number of sesquiterpene synthases. Arch. Biochem. Biophys. 454 (2006) 123–136. [DOI] [PMID: 16970904]
2.	Kumeta, Y. and Ito, M. Characterization of δ-guaiene synthases from cultured cells of Aquilaria, responsible for the formation of the sesquiterpenes in agarwood. Plant Physiol. 154 (2010) 1998–2007. [DOI] [PMID: 20959422]

[EC 4.2.3.87 created 2011]

4.2.3.88

Accepted name:

viridiflorene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = viridiflorene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Other name(s):

TPS31

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (viridiflorene-forming)

Comments:

Viridiflorene is the only product of this enzyme from Solanum lycopersicum.

Links to other databases:

References:

Bleeker, P.M., Spyropoulou, E.A., Diergaarde, P.J., Volpin, H., De Both, M.T., Zerbe, P., Bohlmann, J., Falara, V., Matsuba, Y., Pichersky, E., Haring, M.A. and Schuurink, R.C. RNA-seq discovery, functional characterization, and comparison of sesquiterpene synthases from Solanum lycopersicum and Solanum habrochaites trichomes. Plant Mol. Biol. 77 (2011) 323–336. [DOI] [PMID: 21818683]

[EC 4.2.3.88 created 2011]

4.2.3.89

Accepted name:

(+)-β-caryophyllene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-β-caryophyllene + diphosphate

For diagram of bicyclic and tricyclic sesquiterpenoids derived from humuladienyl cation, click here

Other name(s):

GcoA

Systematic name:

(2Z,6E)-farnesyl-diphosphate diphosphate-lyase [cyclizing, (+)-β-caryophyllene-forming]

Comments:

A multifunctional enzyme which also converts the (+)-β-caryophyllene to (+)-caryolan-1-ol (see EC 4.2.1.138, (+)-caryolan-1-ol synthase). cf. EC 4.2.3.57 (–)-β-caryophyllene synthase.

Links to other databases:

References:

1.	Nakano, C., Horinouchi, S. and Ohnishi, Y. Characterization of a novel sesquiterpene cyclase involved in (+)-caryolan-1-ol biosynthesis in Streptomyces griseus. J. Biol. Chem. 286 (2011) 27980–27987. [DOI] [PMID: 21693706]

[EC 4.2.3.89 created 2011]

4.2.3.90

Accepted name:

5-epi-α-selinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = 5-epi-α-selinene + diphosphate

For diagram of eudesmol and selinene biosynthesis, click here

Glossary:

5-epi-α-selinene = 5β-eudesma-3,11-diene = (2R,4aR,8aS)-1,2,3,4,4a,5,6,8a-octahydro-4a,8-dimethyl-2-(prop-1-en-2-yl)naphthalene
[= 8a-epi-α-selinene which uses naththalene numbering not eudesmane]

Other name(s):

8a-epi-α-selinene synthase; NP1

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, 5-epi-α-selinene-forming)

Comments:

Requires Mg²⁺. The enzyme forms 5-epi-α-selinene possibly via germecrene A or a 1,6-hydride shift mechanism.

Links to other databases:

References:

1.	Agger, S.A., Lopez-Gallego, F., Hoye, T.R. and Schmidt-Dannert, C. Identification of sesquiterpene synthases from Nostoc punctiforme PCC 73102 and Nostoc sp. strain PCC 7120. J. Bacteriol. 190 (2008) 6084–6096. [DOI] [PMID: 18658271]

[EC 4.2.3.90 created 2011]

4.2.3.91

Accepted name:

cubebol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = cubebol + diphosphate

For diagram of cadinane sesquiterpenoid biosynthesis, click here and for diagram of cadinene, cubebol and muuroladiene biosynthesis, click here

Other name(s):

Cop4

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, cubebol-forming)

Comments:

Requires Mg²⁺. The enzyme gives 28% cubebol, 29% (-)-germacrene D, 10% (+)-δ-cadinene and traces of several other sesquiterpenoids. See also EC 4.2.3.75 (–)-germacrene D synthase and EC 4.2.3.13 (+)-δ-cadinene synthase.

Links to other databases:

References:

1.	Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. ChemBioChem 11 (2010) 1093–1106. [DOI] [PMID: 20419721]

[EC 4.2.3.91 created 2011]

4.2.3.92

Accepted name:

(+)-γ-cadinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (+)-γ-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 [(+)-γ-cadinene-forming]

Comments:

The cloned enzyme from the melon, Cucumis melo, gave mainly δ- and γ-cadinene with traces of several other sesquiterpenoids cf. EC 4.2.3.62 (-)-γ-cadinene synthase [(2Z,6E)-farnesyl diphosphate cyclizing]; EC 4.2.3.13 (+)-δ-cadinene synthase.

Links to other databases:

References:

1.	Iijima, Y., Davidovich-Rikanati, R., Fridman, E., Gang, D.R., Bar, E., Lewinsohn, E. and Pichersky, E. The biochemical and molecular basis for the divergent patterns in the biosynthesis of terpenes and phenylpropenes in the peltate glands of three cultivars of basil. Plant Physiol. 136 (2004) 3724–3736. [DOI] [PMID: 15516500]
2.	Portnoy, V., Benyamini, Y., Bar, E., Harel-Beja, R., Gepstein, S., Giovannoni, J.J., Schaffer, A.A., Burger, J., Tadmor, Y., Lewinsohn, E. and Katzir, N. The molecular and biochemical basis for varietal variation in sesquiterpene content in melon (Cucumis melo L.) rinds. Plant Mol. Biol. 66 (2008) 647–661. [DOI] [PMID: 18264780]

[EC 4.2.3.92 created 2011]

4.2.3.93

Accepted name:

δ-guaiene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = δ-guaiene + diphosphate

For diagram of guaiene, α-gurjunene, patchoulol and viridiflorene biosynthesis, click here

Glossary:

δ-guaiene = α-bulnesene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, δ-guaiene-forming)

Comments:

Requires Mg²⁺. In Aquilaria crassna three clones of the enzyme gave about 80% δ-guaiene and 20% α-guaiene (see also EC 4.2.3.87). A fourth clone gave 54% δ-guaiene and 45% α-guaiene [2]. The enzyme from Pogostemon cablin gives 13% δ-guaiene as well as 37% (-)-patchoulol (see EC 4.2.3.70), 13% α-guaiene (see EC 4.2.3.87), and traces of at least ten other sesquiterpenoids [1].

Links to other databases:

References:

1.	Deguerry, F., Pastore, L., Wu, S., Clark, A., Chappell, J. and Schalk, M. The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated with a limited number of sesquiterpene synthases. Arch. Biochem. Biophys. 454 (2006) 123–136. [DOI] [PMID: 16970904]
2.	Kumeta, Y. and Ito, M. Characterization of δ-guaiene synthases from cultured cells of Aquilaria, responsible for the formation of the sesquiterpenes in agarwood. Plant Physiol. 154 (2010) 1998–2007. [DOI] [PMID: 20959422]

[EC 4.2.3.93 created 2011]

4.2.3.94

Accepted name:

γ-curcumene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = γ-curcumene + diphosphate

For diagram of bisabolene biosynthesis, click here and for diagram of γ-curcumene, β-sesquiphellandrene and zingiberene biosynthesis, click here

Other name(s):

PatTpsA (gene name)

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, γ-curcumene-forming)

Comments:

One of five sesquiterpenoid synthases in Pogostemon cablin (patchouli).

Links to other databases:

References:

1.	Deguerry, F., Pastore, L., Wu, S., Clark, A., Chappell, J. and Schalk, M. The diverse sesquiterpene profile of patchouli, Pogostemon cablin, is correlated with a limited number of sesquiterpene synthases. Arch. Biochem. Biophys. 454 (2006) 123–136. [DOI] [PMID: 16970904]

[EC 4.2.3.94 created 2012]

4.2.3.95

Accepted name:

(-)-α-cuprenene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-α-cuprenene + diphosphate

For diagram of biosynthesis of bicyclic sesquiterpenoids derived from bisabolyl cation, click here and for diagram of trichodiene and (–)-α-cuprenene biosynthesis, click here

Other name(s):

Cop6

Systematic name:

(-)-α-cuprenene hydrolase [cyclizing, (-)-α-cuprenene-forming]

Comments:

The enzyme from the fungus Coprinopsis cinerea produces (-)-α-cuprenene with high selectivity.

Links to other databases:

References:

1.	Lopez-Gallego, F., Agger, S.A., Abate-Pella, D., Distefano, M.D. and Schmidt-Dannert, C. Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: catalytic promiscuity and cyclization of farnesyl pyrophosphate geometric isomers. ChemBioChem 11 (2010) 1093–1106. [DOI] [PMID: 20419721]

[EC 4.2.3.95 created 2012]

4.2.3.96

Accepted name:

avermitilol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = avermitilol + diphosphate

For diagram of bicyclogermacrene and avermitilol biosynthesis, click here

Systematic name:

avermitilol hydrolase (cyclizing, avermitilol-forming)

Comments:

Requires Mg²⁺. The recombinent enzyme gives avermitilol (85%) plus traces of germacrene A, germacrene B and viridiflorol. The (1S)-hydrogen of farnesyl diphosphate is retained.

Links to other databases:

References:

1.	Chou, W.K., Fanizza, I., Uchiyama, T., Komatsu, M., Ikeda, H. and Cane, D.E. Genome mining in Streptomyces avermitilis: cloning and characterization of SAV_76, the synthase for a new sesquiterpene, avermitilol. J. Am. Chem. Soc. 132 (2010) 8850–8851. [DOI] [PMID: 20536237]

[EC 4.2.3.96 created 2012]

4.2.3.97

Accepted name:

(-)-δ-cadinene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = (-)-δ-cadinene + diphosphate

For diagram of ent-cadinane sesquiterpenoid biosynthesis, click here

Glossary:

(-)-δ-cadinene = (1R,8aS)-4,7-dimethyl-1-(propan-2-yl)-1,2,3,5,6,8a-hexahydronaphthalene

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (-)-δ-cadinene-forming)

Comments:

The cyclization mechanism involves an intermediate nerolidyl diphosphate leading to a helminthogermacradienyl cation. Following a 1,3-hydride shift of the original 1-pro-S hydrogen of (2E,6E)-farnesyl diphosphate, cyclization and deprotonation gives (-)-δ-cadinene.

Links to other databases:

References:

1.	Hu, Y., Chou, W.K., Hopson, R. and Cane, D.E. Genome mining in Streptomyces clavuligerus: expression and biochemical characterization of two new cryptic sesquiterpene synthases. Chem. Biol. 18 (2011) 32–37. [DOI] [PMID: 21276937]

[EC 4.2.3.97 created 2012]

4.2.3.98

Accepted name:

(+)-T-muurolol synthase

Reaction:

(2E,6E)-farnesyl diphosphate + H₂O = (+)-T-muurolol + diphosphate

For diagram of ent-cadinane sesquiterpenoid biosynthesis, click here

Glossary:

(+)-T-muurolol = (1R,4R,4aS,8aR)-1,6-dimethyl-4-(propan-2-yl)-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (cyclizing, (+)-T-muurolol-forming)

Comments:

The cyclization mechanism involves an intermediate nerolidyl diphosphate leading to a helminthogermacradienyl cation. After a 1,3-hydride shift of the original 1-pro-S hydrogen of farnesyl diphosphate, cyclization and deprotonation result in (+)-T-muurolol.

Links to other databases:

References:

1.	Hu, Y., Chou, W.K., Hopson, R. and Cane, D.E. Genome mining in Streptomyces clavuligerus: expression and biochemical characterization of two new cryptic sesquiterpene synthases. Chem. Biol. 18 (2011) 32–37. [DOI] [PMID: 21276937]

[EC 4.2.3.98 created 2012]

4.2.3.99

Accepted name:

labdatriene synthase

Reaction:

9α-copalyl diphosphate = (12E)-9α-labda-8(17),12,14-triene + diphosphate

For diagram of diterpenoids from 9α-copalyl diphosphate, click here

Glossary:

9α-copalyl diphosphate = syn-copalyl diphosphate = (2E)-3-methyl-5-[(1R,4aS,8aS)-5,5,8a-trimethyl-2-methylidenedecahydronaphthalen-1-yl]pent-2-en-1-yl trihydrogen diphosphate
(12E)-9α-labda-8(17),12,14-triene = (4aS,5R,8aS)-1,1,4a-trimethyl-6-methylidene-5-[(2E)-3-methylpenta-2,4-dien-1-yl]decahydronaphthalene

Other name(s):

OsKSL10 (gene name)

Systematic name:

9α-copalyl-diphosphate diphosphate-lyase [(12E)-9α-labda-8(17),12,14-triene-forming]

Comments:

The enzyme from rice (Oryza sativa), expressed in Escherichia coli, also produces ent-sandaracopimara-8(14),15-diene from ent-copalyl diphosphate, another naturally occuring copalyl isomer in rice (cf. ent-sandaracopimaradiene synthase, EC 4.2.3.29).

Links to other databases:

References:

Morrone, D., Hillwig, M.L., Mead, M.E., Lowry, L., Fulton, D.B. and Peters, R.J. Evident and latent plasticity across the rice diterpene synthase family with potential implications for the evolution of diterpenoid metabolism in the cereals. Biochem. J. 435 (2011) 589–595. [DOI] [PMID: 21323642]

[EC 4.2.3.99 created 2012]

4.2.3.100

Accepted name:

bicyclogermacrene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = bicyclogermacrene + diphosphate

For diagram of bicyclogermacrene and avermitilol biosynthesis, click here

Other name(s):

Ov-TPS4

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (bicyclogermacrene-forming)

Comments:

The enzyme from oregano (Origanum vulgare) gives mainly bicyclogermacrene with Mn²⁺ as a cofactor. With Mg²⁺ a more complex mixture is produced.

Links to other databases:

References:

1.	Crocoll, C., Asbach, J., Novak, J., Gershenzon, J. and Degenhardt, J. Terpene synthases of oregano (Origanum vulgare L.) and their roles in the pathway and regulation of terpene biosynthesis. Plant Mol. Biol. 73 (2010) 587–603. [DOI] [PMID: 20419468]

[EC 4.2.3.100 created 2012]

4.2.3.101

Accepted name:

7-epi-sesquithujene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = 7-epi-sesquithujene + diphosphate

For diagram of biosynthesis of bicyclic sesquiterpenoids derived from bisabolyl cation, click here and for diagram of mechanism, click here

Other name(s):

TPS4-B73

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (7-epi-sesquithujene-forming)

Comments:

The enzyme from Zea mays, variety B73, gives mainly 7-epi-sesquithujene with (S)-β-bisabolene and traces of other sesquiterpenoids, cf. EC 4.2.3.55 (S)-β-bisabolene synthase. It requires Mg²⁺ or Mn²⁺. The product ratio is dependent on which metal ion is present. 7-epi-Sesquithujene is an attractant for the emerald ash borer beetle.

Links to other databases:

References:

Köllner, T.G., Schnee, C., Gershenzon, J. and Degenhardt, J. The variability of sesquiterpenes emitted from two Zea mays cultivars is controlled by allelic variation of two terpene synthase genes encoding stereoselective multiple product enzymes. Plant Cell 16 (2004) 1115–1131. [DOI] [PMID: 15075399]

[EC 4.2.3.101 created 2012]

4.2.3.102

Accepted name:

sesquithujene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = sesquithujene + diphosphate

For diagram of biosynthesis of bicyclic sesquiterpenoids derived from bisabolyl cation, click here and for diagram of mechanism, click here

Other name(s):

TPS5-Del1

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (sesquithujene-forming)

Comments:

The enzyme from Zea mays, variety Delprim, gives mainly sesquithujene with (S)-β-bisabolene and (E)-β-farnesene plus traces of other sesquiterpenoids, cf. EC 4.2.3.55 [(S)-β-bisabolene synthase] and EC 4.2.3.47 (β-farnesene synthase). It requires Mg²⁺ or Mn²⁺. The exact product ratio is dependent on which metal ion is present.

Links to other databases:

References:

[EC 4.2.3.102 created 2012]

4.2.3.103

Accepted name:

ent-isokaurene synthase

Reaction:

ent-copalyl diphosphate = ent-isokaurene + diphosphate

For diagram of biosynthesis of diterpenoids from ent-copalyl diphosphate, click here and for diagram of ent-kaurene and ent-isokaurene, click here

Other name(s):

OsKSL5i; OsKSL6

Systematic name:

ent-copalyl-diphosphate diphosphate-lyase (cyclizing, ent-isokaurene-forming)

Comments:

Two enzymes of the rice sub-species Oryza sativa ssp. indica, OsKSL5 and OsKSL6, produce ent-isokaurene. A variant of OsKSL5 from the sub-species Oryza sativa ssp. japonica produces ent-pimara-8(14),15-diene instead [cf. EC 4.2.3.30, ent-pimara-8(14),15-diene synthase].

Links to other databases:

References:

1.	Xu, M., Wilderman, P.R., Morrone, D., Xu, J., Roy, A., Margis-Pinheiro, M., Upadhyaya, N.M., Coates, R.M. and Peters, R.J. Functional characterization of the rice kaurene synthase-like gene family. Phytochemistry 68 (2007) 312–326. [DOI] [PMID: 17141283]
2.	Xu, M., Wilderman, P.R. and Peters, R.J. Following evolution’s lead to a single residue switch for diterpene synthase product outcome. Proc. Natl. Acad. Sci. USA 104 (2007) 7397–7401. [DOI] [PMID: 17456599]

[EC 4.2.3.103 created 2012]

4.2.3.104

Accepted name:

α-humulene synthase

Reaction:

(2E,6E)-farnesyl diphosphate = α-humulene + diphosphate

For diagram of sesquiterpenoid biosynthesis based on humulene, click here

Other name(s):

ZSS1

Systematic name:

(2E,6E)-farnesyl-diphosphate diphosphate-lyase (α-humulene-forming)

Comments:

The enzyme from Zingiber zerumbet, shampoo ginger, also gives traces of β-caryophyllene.

Links to other databases:

References:

Yu, F., Okamto, S., Nakasone, K., Adachi, K., Matsuda, S., Harada, H., Misawa, N. and Utsumi, R. Molecular cloning and functional characterization of α-humulene synthase, a possible key enzyme of zerumbone biosynthesis in shampoo ginger (Zingiber zerumbet Smith). Planta 227 (2008) 1291–1299. [DOI] [PMID: 18273640]

[EC 4.2.3.104 created 2012]

4.2.3.105

Accepted name:

tricyclene synthase

Reaction:

geranyl diphosphate = tricyclene + diphosphate

For diagram of bornane and related monoterpenoids, click here

Other name(s):

TPS3

Systematic name:

geranyl-diphosphate diphosphate-lyase (cyclizing; tricyclene-forming)

Comments:

The enzyme from Solanum lycopersicum (tomato) gives a mixture of tricyclene, camphene, β-myrcene, limonene, and traces of several other monoterpenoids. See EC 4.2.3.117. (-)-camphene synthase, EC 4.2.3.15, myrcene synthase and EC 4.2.3.16, (4S)-limonene synthase.

Links to other databases:

References:

1.	Falara, V., Akhtar, T.A., Nguyen, T.T., Spyropoulou, E.A., Bleeker, P.M., Schauvinhold, I., Matsuba, Y., Bonini, M.E., Schilmiller, A.L., Last, R.L., Schuurink, R.C. and Pichersky, E. The tomato terpene synthase gene family. Plant Physiol. 157 (2011) 770–789. [DOI] [PMID: 21813655]

[EC 4.2.3.105 created 2012]

4.2.3.106

Accepted name:

(E)-β-ocimene synthase

Reaction:

geranyl diphosphate = (E)-β-ocimene + diphosphate

Glossary:

(E)-β-ocimene = (3E)-3,7-dimethylocta-1,3,6-triene

Other name(s):

β-ocimene synthase; AtTPS03; ama0a23; LjEβOS; MtEBOS

Systematic name:

geranyl-diphosphate diphosphate-lyase [(E)-β-ocimene-forming]

Comments:

Widely distributed in plants, which release β-ocimene when attacked by herbivorous insects.

Links to other databases:

References:

1.	Faldt, J., Arimura, G., Gershenzon, J., Takabayashi, J. and Bohlmann, J. Functional identification of AtTPS03 as (E)-β-ocimene synthase: a monoterpene synthase catalyzing jasmonate- and wound-induced volatile formation in Arabidopsis thaliana. Planta 216 (2003) 745–751. [DOI] [PMID: 12624761]
2.	Dudareva, N., Martin, D., Kish, C.M., Kolosova, N., Gorenstein, N., Faldt, J., Miller, B. and Bohlmann, J. (E)-β-ocimene and myrcene synthase genes of floral scent biosynthesis in snapdragon: function and expression of three terpene synthase genes of a new terpene synthase subfamily. Plant Cell 15 (2003) 1227–1241. [DOI] [PMID: 12724546]
3.	Arimura, G., Ozawa, R., Kugimiya, S., Takabayashi, J. and Bohlmann, J. Herbivore-induced defense response in a model legume. Two-spotted spider mites induce emission of (E)-β-ocimene and transcript accumulation of (E)-β-ocimene synthase in Lotus japonicus. Plant Physiol. 135 (2004) 1976–1983. [DOI] [PMID: 15310830]
4.	Navia-Gine, W.G., Yuan, J.S., Mauromoustakos, A., Murphy, J.B., Chen, F. and Korth, K.L. Medicago truncatula (E)-β-ocimene synthase is induced by insect herbivory with corresponding increases in emission of volatile ocimene. Plant Physiol. Biochem. 47 (2009) 416–425. [DOI] [PMID: 19249223]

[EC 4.2.3.106 created 2012]

4.2.3.107

Accepted name:

(+)-car-3-ene synthase

Reaction:

geranyl diphosphate = (+)-car-3-ene + diphosphate

For diagram of monoterpenoid biosynthesis, click here

Glossary:

(+)-car-3-ene = (1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene

Other name(s):

3-carene cyclase; 3-carene synthase; 3CAR; (+)-3-carene synthase

Systematic name:

geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-car-3-ene-forming]

Comments:

The enzyme reacts with (3S)-linalyl diphosphate twice as rapidly as geranyl diphosphate, but 25 times as rapidly as (3R)-linalyl diphosphate. It is assumed that (3S)-linalyl diphosphate is normally formed as an enzyme bound intermediate in the reaction. In the reaction the 5-pro-R hydrogen of geranyl diphosphate is eliminated during cyclopropane ring formation [1,2]. In Picea abies (Norway spruce) and Picea sitchensis (Sitka spruce) terpinolene is also formed [4,6]. See EC 4.2.3.113 terpinolene synthase. (+)-Car-3-ene is associated with resistance of Picea sitchensis (Sitka spruce) to white pine weevil [6].

Links to other databases:

References:

1.	Savage, T.J. and Croteau, R. Biosynthesis of monoterpenes: regio- and stereochemistry of (+)-3-carene biosynthesis. Arch. Biochem. Biophys. 305 (1993) 581–587. [DOI] [PMID: 8373196]
2.	Savage, T.J., Ichii, H., Hume, S.D., Little, D.B. and Croteau, R. Monoterpene synthases from gymnosperms and angiosperms: stereospecificity and inactivation by cysteinyl- and arginyl-directed modifying reagents. Arch. Biochem. Biophys. 320 (1995) 257–265. [DOI] [PMID: 7625832]
3.	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]
4.	Faldt, J., Martin, D., Miller, B., Rawat, S. and Bohlmann, J. Traumatic resin defense in Norway spruce (Picea abies): methyl jasmonate-induced terpene synthase gene expression, and cDNA cloning and functional characterization of (+)-3-carene synthase. Plant Mol. Biol. 51 (2003) 119–133. [PMID: 12602896]
5.	Hamberger, B., Hall, D., Yuen, M., Oddy, C., Hamberger, B., Keeling, C.I., Ritland, C., Ritland, K. and Bohlmann, J. Targeted isolation, sequence assembly and characterization of two white spruce (Picea glauca) BAC clones for terpenoid synthase and cytochrome P₄₅₀ genes involved in conifer defence reveal insights into a conifer genome. BMC Plant Biol. 9:106 (2009). [DOI] [PMID: 19656416]
6.	Hall, D.E., Robert, J.A., Keeling, C.I., Domanski, D., Quesada, A.L., Jancsik, S., Kuzyk, M.A., Hamberger, B., Borchers, C.H. and Bohlmann, J. An integrated genomic, proteomic and biochemical analysis of (+)-3-carene biosynthesis in Sitka spruce (Picea sitchensis) genotypes that are resistant or susceptible to white pine weevil. Plant J. 65 (2011) 936–948. [DOI] [PMID: 21323772]

[EC 4.2.3.107 created 2012]

4.2.3.108

Accepted name:

1,8-cineole synthase

Reaction:

geranyl diphosphate + H₂O = 1,8-cineole + diphosphate

For diagram of menthane monoterpenoid biosynthesis, click here

Glossary:

1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane

Other name(s):

1,8-cineole cyclase; geranyl pyrophoshate:1,8-cineole cyclase; 1,8-cineole synthetase

Systematic name:

geranyl-diphosphate diphosphate-lyase (cyclizing, 1,8-cineole-forming)

Comments:

Requires Mn²⁺ or Zn²⁺. Mg²⁺ is less effective than either. 1,8-Cineole is the main product from the enzyme with just traces of other monoterpenoids. The oxygen atom is derived from water. The reaction proceeds via linalyl diphosphate and α-terpineol, the stereochemistry of both depends on the organism. However neither intermediate can substitute for geranyl diphosphate. The reaction in Salvia officinalis (sage) proceeds via (–)-(3R)-linalyl diphosphate [1-3] while that in Arabidopsis (rock cress) proceeds via (+)-(3S)-linalyl diphosphate [4].

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 110637-19-9

References:

1.	Croteau, R., Alonso, W.R., Koepp, A.E. and Johnson, M.A. Biosynthesis of monoterpenes: partial purification, characterization, and mechanism of action of 1,8-cineole synthase. Arch. Biochem. Biophys. 309 (1994) 184–192. [DOI] [PMID: 8117108]
2.	Wise, M.L., Savage, T.J., Katahira, E. and Croteau, R. Monoterpene synthases from common sage (Salvia officinalis). cDNA isolation, characterization, and functional expression of (+)-sabinene synthase, 1,8-cineole synthase, and (+)-bornyl diphosphate synthase. J. Biol. Chem. 273 (1998) 14891–14899. [DOI] [PMID: 9614092]
3.	Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203–211. [DOI] [PMID: 12941302]
4.	Chen, F., Ro, D.K., Petri, J., Gershenzon, J., Bohlmann, J., Pichersky, E. and Tholl, D. Characterization of a root-specific Arabidopsis terpene synthase responsible for the formation of the volatile monoterpene 1,8-cineole. Plant Physiol. 135 (2004) 1956–1966. [DOI] [PMID: 15299125]
5.	Keszei, A., Brubaker, C.L., Carter, R., Kollner, T., Degenhardt, J. and Foley, W.J. Functional and evolutionary relationships between terpene synthases from Australian Myrtaceae. Phytochemistry 71 (2010) 844–852. [DOI] [PMID: 20399476]

[EC 4.2.3.108 created 2012]

4.2.3.109

Accepted name:

(-)-sabinene synthase

Reaction:

geranyl diphosphate = (-)-sabinene + diphosphate

For diagram of thujane monoterpenoid biosynthesis, click here

Glossary:

(-)-sabinene = (1S,5S)-1-isopropyl-4-methylenebicyclo[3.1.0]hexane

Systematic name:

geranyl-diphosphate diphosphate-lyase [cyclizing, (-)-sabinene-forming]

Comments:

Requires Mg²⁺. Isolated from Pinus contorta (lodgepole pine) as cyclase I [1] and from Conocephalum conicum (liverwort) [2].

Links to other databases:

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.	Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203–211. [DOI] [PMID: 12941302]

[EC 4.2.3.109 created 2012]

4.2.3.110

Accepted name:

(+)-sabinene synthase

Reaction:

geranyl diphosphate = (+)-sabinene + diphosphate

For diagram of thujane monoterpenoid biosynthesis, click here

Glossary:

(+)-sabinene = (+)-thuj-4(10)-ene = (1R,5R)-1-isopropyl-4-methylenebicyclo[3.1.0]hexane

Other name(s):

Systematic name:

geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-sabinene-forming]

Comments:

Isolated from Salvia officinalis (sage). The recombinant enzyme gave 63% (+)-sabinene, 21% γ-terpinene, and traces of other monoterpenoids. See EC 4.2.3.114 γ-terpinene synthase.

Links to other databases:

References:

1.	Wise, M.L., Savage, T.J., Katahira, E. and Croteau, R. Monoterpene synthases from common sage (Salvia officinalis). cDNA isolation, characterization, and functional expression of (+)-sabinene synthase, 1,8-cineole synthase, and (+)-bornyl diphosphate synthase. J. Biol. Chem. 273 (1998) 14891–14899. [DOI] [PMID: 9614092]
2.	Peters, R.J. and Croteau, R.B. Alternative termination chemistries utilized by monoterpene cyclases: chimeric analysis of bornyl diphosphate, 1,8-cineole, and sabinene synthases. Arch. Biochem. Biophys. 417 (2003) 203–211. [DOI] [PMID: 12941302]

[EC 4.2.3.110 created 2012]

4.2.3.111

Accepted name:

(-)-α-terpineol synthase

Reaction:

geranyl diphosphate + H₂O = (-)-α-terpineol + diphosphate

For diagram of menthane monoterpenoid biosynthesis, click here

Systematic name:

geranyl-diphosphate diphosphate-lyase [cyclizing, (-)-α-terpineol-forming]

Comments:

The enzyme has been characterized from Vitis vinifera (grape). Also forms some 1,8-cineole and traces of other monoterpenoids.

Links to other databases: