EC |
1.1.1.241 |
Accepted name: |
6-endo-hydroxycineole dehydrogenase |
Reaction: |
6-endo-hydroxycineole + NAD+ = 6-oxocineole + NADH + H+ |
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For diagram of 1,8-cineole catabolism, click here |
Systematic name: |
6-endo-hydroxycineole:NAD+ 6-oxidoreductase |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 122933-68-0 |
References: |
1. |
Williams, D.R., Trudgill, P.W. and Taylor, D.G. Metabolism of 1,8-cineole by Rhodococcus species: ring cleavage reactions. J. Gen. Microbiol. 135 (1989) 1957–1967. |
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[EC 1.1.1.241 created 1992] |
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EC |
1.14.13.51 |
Accepted name: |
6-oxocineole dehydrogenase |
Reaction: |
6-oxocineole + NADPH + H+ + O2 = 1,6,6-trimethyl-2,7-dioxabicyclo[3.2.2]nonan-3-one + NADP+ + H2O |
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For diagram of 1,8-cineole catabolism, click here |
Other name(s): |
6-oxocineole oxygenase |
Systematic name: |
6-oxocineole,NADPH:oxygen oxidoreductase |
Comments: |
The product undergoes non-enzymic cleavage and subsequent ring closure to form the lactone 4,5-dihydro-5,5-dimethyl-4-(3-oxobutyl)furan-2(3H)-one. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number: 122933-80-6 |
References: |
1. |
Williams, D.R., Trudgill, P.W. and Taylor, D.G. Metabolism of 1,8-cineole by Rhodococcus species: ring cleavage reactions. J. Gen. Microbiol. 135 (1989) 1957–1967. |
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[EC 1.14.13.51 created 1992] |
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EC
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1.14.13.156
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Transferred entry: | 1,8-cineole 2-endo-monooxygenase. Now EC 1.14.14.133, 1,8-cineole 2-endo-monooxygenase
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[EC 1.14.13.156 created 2012, deleted 2018] |
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EC
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1.14.13.157
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Transferred entry: | 1,8-cineole 2-exo-monooxygenase. Now EC 1.14.14.56, 1,8-cineole 2-exo-monooxygenase
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[EC 1.14.13.157 created 2012, deleted 2017] |
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EC |
1.14.14.56 |
Accepted name: |
1,8-cineole 2-exo-monooxygenase |
Reaction: |
1,8-cineole + [reduced NADPH—hemoprotein reductase] + O2 = 2-exo-hydroxy-1,8-cineole + [oxidized NADPH—hemoprotein reductase] + H2O |
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For diagram of 1,8-cineole catabolism, click here |
Glossary: |
1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
2-exo-hydroxy-1,8-cineole = (1R,4S,6S)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol |
Other name(s): |
CYP3A4 |
Systematic name: |
1,8-cineole,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (2-exo-hydroxylating) |
Comments: |
A cytochrome P-450 (heme-thiolate) protein. The mammalian enzyme, expressed in liver microsomes, performs a variety of oxidation reactions of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. cf. EC 1.14.14.55, quinine 3-monooxygenase, EC 1.14.14.57, taurochenodeoxycholate 6-hydroxylase and EC 1.14.14.73, albendazole monooxygenase (sulfoxide-forming). |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Miyazawa, M., Shindo, M. and Shimada, T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated from Eucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab. Dispos. 29 (2001) 200–205. [PMID: 11159812] |
2. |
Miyazawa, M. and Shindo, M. Biotransformation of 1,8-cineole by human liver microsomes. Nat. Prod. Lett. 15 (2001) 49–53. [DOI] [PMID: 11547423] |
3. |
Miyazawa, M., Shindo, M. and Shimada, T. Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes. Xenobiotica 31 (2001) 713–723. [DOI] [PMID: 11695850] |
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[EC 1.14.14.56 created 2012 as EC 1.14.13.157, transferred 2017 to EC 1.14.14.56, modified 2018] |
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EC |
1.14.14.133 |
Accepted name: |
1,8-cineole 2-endo-monooxygenase |
Reaction: |
1,8-cineole + [reduced flavodoxin] + O2 = 2-endo-hydroxy-1,8-cineole + [oxidized flavodoxin] + H2O |
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For diagram of 1,8-cineole catabolism, click here |
Glossary: |
1,8-cineole = 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane
2-endo-hydroxy-1,8-cineole = (1R,4S,6R)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol |
Other name(s): |
P450cin; CYP176A; CYP176A1 |
Systematic name: |
1,8-cineole,[reduced flavodoxin]:oxygen oxidoreductase (2-endo-hydroxylating) |
Comments: |
A cytochrome P-450 (heme-thiolate) protein that uses a flavodoxin-like redox partner to reduce the heme iron. Isolated from the bacterium Citrobacter braakii, which can use 1,8-cineole as the sole source of carbon. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Hawkes, D.B., Adams, G.W., Burlingame, A.L., Ortiz de Montellano, P.R. and De Voss, J.J. Cytochrome P450cin (CYP176A), isolation, expression, and characterization. J. Biol. Chem. 277 (2002) 27725–27732. [DOI] [PMID: 12016226] |
2. |
Meharenna, Y.T., Li, H., Hawkes, D.B., Pearson, A.G., De Voss, J. and Poulos, T.L. Crystal structure of P450cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450cam. Biochemistry 43 (2004) 9487–9494. [DOI] [PMID: 15260491] |
3. |
Kimmich, N., Das, A., Sevrioukova, I., Meharenna, Y., Sligar, S.G. and Poulos, T.L. Electron transfer between cytochrome P450cin and its FMN-containing redox partner, cindoxin. J. Biol. Chem. 282 (2007) 27006–27011. [DOI] [PMID: 17606612] |
4. |
Meharenna, Y.T., Slessor, K.E., Cavaignac, S.M., Poulos, T.L. and De Voss, J.J. The critical role of substrate-protein hydrogen bonding in the control of regioselective hydroxylation in p450cin. J. Biol. Chem. 283 (2008) 10804–10812. [DOI] [PMID: 18270198] |
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[EC 1.14.14.133 created 2012 as EC 1.14.13.156, transferred 2018 to EC 1.14.14.133] |
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EC |
4.2.3.108 |
Accepted name: |
1,8-cineole synthase |
Reaction: |
geranyl diphosphate + H2O = 1,8-cineole + diphosphate |
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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, 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] |
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[EC 4.2.3.108 created 2012] |
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EC |
4.2.3.109 |
Accepted name: |
(-)-sabinene synthase |
Reaction: |
geranyl diphosphate = (-)-sabinene + diphosphate |
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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: |
BRENDA, EXPASY, KEGG, MetaCyc |
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] |
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[EC 4.2.3.109 created 2012] |
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EC |
4.2.3.110 |
Accepted name: |
(+)-sabinene synthase |
Reaction: |
geranyl diphosphate = (+)-sabinene + diphosphate |
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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): |
SS |
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: |
BRENDA, EXPASY, KEGG, MetaCyc |
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] |
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[EC 4.2.3.110 created 2012] |
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EC |
4.2.3.111 |
Accepted name: |
(-)-α-terpineol synthase |
Reaction: |
geranyl diphosphate + H2O = (-)-α-terpineol + diphosphate |
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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: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB |
References: |
1. |
Martin, D.M. and Bohlmann, J. Identification of Vitis vinifera (-)-α-terpineol synthase by in silico screening of full-length cDNA ESTs and functional characterization of recombinant terpene synthase. Phytochemistry 65 (2004) 1223–1229. [DOI] [PMID: 15184006] |
2. |
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] |
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[EC 4.2.3.111 created 2012] |
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EC |
5.5.1.8 |
Accepted name: |
(+)-bornyl diphosphate synthase |
Reaction: |
geranyl diphosphate = (+)-bornyl diphosphate |
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For diagram of bornane and related monoterpenoids, click here |
Glossary: |
(+)-bornyl diphosphate = (1R,2S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl diphosphate |
Other name(s): |
bornyl pyrophosphate synthase (ambiguous); bornyl pyrophosphate synthetase (ambiguous); (+)-bornylpyrophosphate cyclase; geranyl-diphosphate cyclase (ambiguous); (+)-bornyl-diphosphate lyase (decyclizing) |
Systematic name: |
(+)-bornyl-diphosphate lyase (ring-opening) |
Comments: |
Requires Mg2+. The enzyme from Salvia officinalis (sage) can also use (3R)-linalyl diphosphate or more slowly neryl diphosphate in vitro [3]. The reaction proceeds via isomeration of geranyl diphosphate to (3R)-linalyl diphosphate. The oxygen and phosphorus originally linked to C-1 of geranyl diphosphate end up linked to C-2 of (+)-bornyl diphosphate [3]. cf. EC 5.5.1.22 [(–)-bornyl diphosphate synthase]. |
Links to other databases: |
BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 72668-91-8 |
References: |
1. |
Croteau, R. and Karp, F. Biosynthesis of monoterpenes: preliminary characterization of bornyl pyrophosphate synthetase from sage (Salvia officinalis) and demonstration that geranyl pyrophosphate is the preferred substrate for cyclization. Arch. Biochem. Biophys. 198 (1979) 512–522. [DOI] [PMID: 42356] |
2. |
Croteau, R., Gershenzon, J., Wheeler, C.J. and Satterwhite, D.M. Biosynthesis of monoterpenes: stereochemistry of the coupled isomerization and cyclization of geranyl pyrophosphate to camphane and isocamphane monoterpenes. Arch. Biochem. Biophys. 277 (1990) 374–381. [DOI] [PMID: 2178556] |
3. |
Croteau, R., Satterwhite, D.M., Cane, D.E. and Chang, C.C. Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (-)-linalyl pyrophosphate to (+)- and (-)-bornyl pyrophosphate. J. Biol. Chem. 261 (1986) 13438–13445. [PMID: 3759972] |
4. |
Croteau, R., Felton, N.M. and Wheeler, C.J. Stereochemistry at C-1 of geranyl pyrophosphate and neryl pyrophosphate in the cyclization to (+)- and (-)-bornyl pyrophosphate. J. Biol. Chem. 260 (1985) 5956–5962. [PMID: 3997807] |
5. |
Croteau, R.B., Shaskus, J.J., Renstrom, B., Felton, N.M., Cane, D.E., Saito, A. and Chang, C. Mechanism of the pyrophosphate migration in the enzymatic cyclization of geranyl and linalyl pyrophosphates to (+)- and (-)-bornyl pyrophosphates. Biochemistry 24 (1985) 7077–7085. [PMID: 4084562] |
6. |
McGeady, P. and Croteau, R. Isolation and characterization of an active-site peptide from a monoterpene cyclase labeled with a mechanism-based inhibitor. Arch. Biochem. Biophys. 317 (1995) 149–155. [DOI] [PMID: 7872777] |
7. |
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] |
8. |
Whittington, D.A., Wise, M.L., Urbansky, M., Coates, R.M., Croteau, R.B. and Christianson, D.W. Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase. Proc. Natl. Acad. Sci. USA 99 (2002) 15375–15380. [DOI] [PMID: 12432096] |
9. |
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] |
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[EC 5.5.1.8 created 1984, modified 2012] |
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