Accepted name: dihydrocarveol dehydrogenase

Reaction: dihydrocarveol + NAD⁺ = dihydrocarvone + NADH + H⁺

For diagram click here.

Systematic name: dihydrocarveol:NAD⁺ oxidoreductase

Comments: All isomers of dihydrocarveol are metabolised.

References:

1. van der Werf, M.J. and Boot, A.M. Metabolism of carveol and dihydrocarveol in Rhodococcus erythropolis DCL14. Microbiology 146 (2000) 1129-1141. [PMID: 10832640]

EC 1.1.1.297

Accepted name: limonene-1,2-diol dehydrogenase

Reaction: menth-8-ene-1,2-diol + NADP⁺ = 1-hydoxymenth-8-en-2-one + NADPH + H⁺

For diagram click here.

Systematic name: menth-8-ene-1,2-diol:NADP⁺ oxidoreductase

Comments: Both (1R,2R,4S)- and (1S,2S,4R)-menth-8-ene-1,2-diol are metabolised.

References:

1. van der Werf, M.J., Swarts, H.J. and de Bont, J.A. Rhodococcus erythropolis DCL14 contains a novel degradation pathway for limonene. Appl. Environ. Microbiol. 65 (1999) 2092-2102. [PMID: 10224006]

EC 1.1.1.w (–)-endo-fenchol dehydrogenase

Reaction: (–)-endo-fenchol + NAD(P)⁺ = (+)-fenchone + NAD(P)H + H⁺

Other name(s): l-endo-fenchol dehydrogenase; FDH

For diagram click here.

Systematic name: (–)-endo-fenchol:NAD(P)⁺ oxidoreductase

Comments: Requires Mn²⁺.

Note This was EC 1.1.1.182 which is now stated to be EC 1.1.1.198, EC 1.1.1.227 and EC 1.1.1.228. I do not agree. It could only be equivalent to one of the three and I know of no evidence that any of them are able to oxidise fenchol.

References:

1. Croteau, R. and Felton, N.M. Substrate specificity of monoterpenol dehydrogenases from Foeniculum vulgare and Tanacetum vulgare. Phytochemistry 19 (1980) 1343-1347.

2. Croteau, R., Felton, M. and Ronald, R.C. Biosynthesis of monoterpenes: conversion of the acyclic precursors geranyl pyrophosphate and neryl pyrophosphate to the rearranged monoterpenes fenchol and fenchone by a soluble enzyme preparation from fennel (Foeniculum vulgare). Arch. Biochem. Biophys. 200 (1980) 524-533. [PMID: 7436420]

EC 1.1.1.y

Accepted name: 10-hydroxygeraniol dehydrogenase

Reaction: 8-hydroxygeraniol + 2 NADP⁺ = 8-oxogeranial + 2 NADPH + 2 H⁺

For diagram click here.

Other name(s): acyclic monoterpene primary alcohol:NADP⁺ oxidoreductase

Systematic name: 8-hydroxygeraniol:NADP⁺ oxidoreductase

Comments: Contains Zn²⁺. Also acts on geraniol, nerol and citronellol. May be identical to EC 1.1.1.183 geraniol dehydrogenase. The recommended numbering of geraniol gives 8-hydroxygeraniol as the substrate rather than 10-hydroxygeraniol as implied by the accepted name. See prenol nomenclature Pr-1.

References:

1. Ikeda, H., Esaki, N., Nakai, S., Hashimoto, K., Uesato, S., Soda, K. and Fujita, T. Acyclic monoterpene primary alcohol:NADP+ oxidoreductase of Rauwolfia serpentina cells: the key enzyme in biosynthesis of monoterpene alcohols. J. Biochem. (Tokyo) 109 (1991) 341-347. [PMID: 1864846]

2. Hallahan, D.L., West, J.M., Wallsgrove, R.M., Smiley, D.W., Dawson, G.W., Pickett, J.A. and Hamilton, J.G. Purification and characterization of an acyclic monoterpene primary alcohol:NADP⁺ oxidoreductase from catmint (Nepeta racemosa). Arch. Biochem. Biophys. 318 (1995) 105-112. [PMID: 7726550]

EC 1.1.1.z

Accepted name: 5-exo-hydroxycamphor dehydrogenase

Reaction: 5-exo-hydroxycamphor + NAD⁺ = bornane-2,5-dione + NADH + H⁺

For diagram click here.

Systematic name: 5-exo-hydroxycamphor:NADP⁺ oxidoreductase

Comments: Contains Zn²⁺.

References:

1. Aramaki, H., Koga, H., Sagara, Y., Hosoi, M. and Horiuchi, T. Complete nucleotide sequence of the 5-exo-hydroxycamphor dehydrogenase gene on the CAM plasmid of Pseudomonas putida (ATCC 17453). Biochim. Biophys. Acta 1174 (1993) 91-94. [PMID: 8334169]

EC 1.3.1.82

Accepted name: (–)-isopiperitenone reductase

Reaction: (+)-cis-isopulegone + NADP⁺ = (–)-isopiperitenone + NADPH + H⁺

For diagram click here.

Systematic name: (+)-cis-isopulegone:NADP⁺ oxidoreductase

References:

1. Croteau, R. and Venkatachalam, K.V. Metabolism of monoterpenes: demonstration that (+)-cis-isopulegone, not piperitenone, is the key intermediate in the conversion of (–)-isopiperitenone to (+)-pulegone in peppermint (Mentha piperita). Arch. Biochem. Biophys. 249 (1986) 306-315. [PMID: 3755881]

2. Ringer, K.L., McConkey, M.E., Davis, E.M., Rushing, G.W. and Croteau, R. Monoterpene double-bond reductases of the (–)-menthol biosynthetic pathway: isolation and characterization of cDNAs encoding (–)-isopiperitenone reductase and (+)-pulegone reductase of peppermint. Arch. Biochem. Biophys. 418 (2003) 80-92. [PMID: 13679086]

EC 1.3.1.y

Accepted name: (+)-pulegone reductase

Reaction: (–)-menthone + NADP⁺ = (+)-pulegone + NADPH + H⁺

For diagram click here.

Systematic name: (+)-pulegone:NADP⁺ oxidoreductase

References:

1. Ringer, K.L., McConkey, M.E., Davis, E.M., Rushing, G.W. and Croteau, R. Monoterpene double-bond reductases of the (–)-menthol biosynthetic pathway: isolation and characterization of cDNAs encoding (–)-isopiperitenone reductase and (+)-pulegone reductase of peppermint. Arch. Biochem. Biophys. 418 (2003) 80-92. [PMID: 13679086]

EC 1.3.99.25

Accepted name: carvone reductase

Reaction: (–)-carvone + acceptor = dihydrocarvone + reduced acceptor

For diagram click here.

Systematic name: (–)-carvone:acceptor 1,6-oxidoreductase

Comments: The cofactor is unknown.

References:

1. van der Werf, M.J. and Boot, A.M. Metabolism of carveol and dihydrocarveol in Rhodococcus erythropolis DCL14. Microbiology 146 (2000) 1129-1141. [PMID: 10832640]

EC 1.14.13.k

Accepted name: 1,8-cineole 2-exo-monooxygenase

Reaction: 1,8-cineole + NADPH + H⁺ + O₂ = 2-exo-hydroxy-1,8-cineole + NADP⁺ + H₂O

For diagram click here.

Systematic name: 1,8-cineole,NADPH:oxygen oxidoreductase (2-exo-hydroxylating)

Comments: A heme-thiolate protein (P-450).

References:

1. Miyazawa, M. and Shindo, M. Biotransformation of 1,8-cineole by human liver microsomes. Nat. Prod. Lett. 15 (2001) 49-53. [PMID: 11547423]

EC 1.14.13.l

Accepted name: limonene 1,2-monooxygenase

Reaction: limonene + NADH + H⁺ + O₂ = 1,2-epoxymenth-8-ene + NAD⁺ + H₂O

For diagram click here.

Systematic name: limonene,NADH:oxygen oxidoreductase

Comments: A flavoprotein (FAD). Both (+)-(R)- and (–)-(S)limonene are metabolised.

References:

1. van der Werf, M.J., Swarts, H.J. and de Bont, J.A. Rhodococcus erythropolis DCL14 contains a novel degradation pathway for limonene. Appl. Environ. Microbiol. 65 (1999) 2092-2102. [PMID: 10224006]

EC 1.14.13.105

Accepted name: monocyclic monoterpene ketone monooxygenase

Reaction: (1) menthone + NADPH + H⁺ + O₂ = 7-isopropyl-4-methyloxepan-2-one + NADP⁺ + H₂O
(2) dihydrocarvone + NADPH + H⁺ + O₂ = 4-isopropenyl-7-methyloxepan-2-one + NADP⁺ + H₂O
(3) 1-hydroxymenth-8-en-2-one + NADPH + H⁺ + O₂ = 7-hydroxy-4-isopropenyl-7-methyloxepan-2-one + NADP⁺ + H₂O

For diagram in menthone click here, dihydrocarvone click here or limonene catabolism click here.

Other name(s): 1-hydroxy-2-oxolimonene 1,2-monooxygenase; dihydrocarvone 1,2-monooxygenase; MMKMO

Systematic name: menthanone,NADH:oxygen oxidoreductase

Comments: A flavoprotein (FAD). Both (1R,4S)- and (1S,4R)-1-hydroxymenth-8-en-2-one are metabolised and the product is spontaneously converted into 3-isopropenyl-6-oxoheptanoate. Similar Baeyer-Villiger reactions occur with menthone and dihydrocarvone. Many other similar molecules also react.

References:

1. van der Werf, M.J., Swarts, H.J. and de Bont, J.A. Rhodococcus erythropolis DCL14 contains a novel degradation pathway for limonene. Appl. Environ. Microbiol. 65 (1999) 2092-2102. [PMID: 10224006]

2. Van Der Werf, M.J. Rhodococcus erythropolis DCL14 involved in three different monocyclic monoterpene degradation pathways. Biochem. J. 347 (2000) 693-701. [PMID: 10769172]

3. van der Werf, M.J. and Boot, A.M. Metabolism of carveol and dihydrocarveol in Rhodococcus erythropolis DCL14. Microbiology 146 (2000) 1129-1141. [PMID: 10832640]

EC 1.14.13.n

Accepted name: α-pinene monooxygenase

Reaction: (–)-α-pinene + NADH + H⁺ + O₂ = α-pinene oxide + NAD⁺ + H₂O

For diagram click here.

Systematic name: (–)-α-pinene,NADH:oxygen oxidoreductase

References:

1. Colocousi, A. and Leak, D.J. Cloning and expression of the α-pinene monooxygenase gene from Pseudomonas fuorescence. NCIMB 11671. Environ. Technol. (1994) 144-157.

2. Colocousi, A. Saqib, K.M. and Leak, D.J. Mutants of Pseudomonas fuorescence NCIMB 11671 defective in the catabolism of α-pinene. Appl. Microbiol. Biotechnol. 45 (1996) 822-830.

EC 1.14.13.104

Accepted name: (+)-menthofuran synthase

Reaction: (+)-pulegone + NADPH + H⁺ + O₂ = (+)-menthofuran + NADP⁺ + H₂O

For diagram click here or mechanism click here.

Other name(s): (+)-pulegone 9-hydroxylase; (+)-MFS

Systematic name: (+)-pulegone,NADPH:oxygen oxidoreductase (9-hydroxylating)

Comments: A heme-thiolate protein (P-450).

References:

1. Bertea, C.M., Schalk, M., Karp, F., Maffei, M. and Croteau, R. Demonstration that menthofuran synthase of mint (Mentha) is a cytochrome P450 monooxygenase: cloning, functional expression, and characterization of the responsible gene. Arch. Biochem. Biophys. 390 (2001) 279-286. [PMID: 11396930]

2. Mahmoud, S.S. and Croteau, R.B. Menthofuran regulates essential oil biosynthesis in peppermint by controlling a downstream monoterpene reductase. Proc. Natl. Acad. Sci. USA 100 (2003) 14481-14486. [PMID: 14623962]

EC 1.14.13.s

Accepted name: 1,8-cineole 2-monooxygenase

Reaction: 1,8-cineole + NADPH + H⁺ + O₂ = 2-endo-hydroxy-1,8-cineole + NADP⁺ + H₂O

For diagram click here.

Other name(s): P450_cin; CYP176A; CYP176A1

Systematic name: 1,8-cineole,NADPH:oxygen oxidoreductase (2-endo-hydroxylating)

Comments: A heme-thiolate protein (P-450) which uses a flavodoxin-like redox partner to reduce the heme iron.

References:

1. Miyazawa, M., Shindo, M. and Shimada, T. Oxidation of 1,8-cineole, the monoterpene cyclic ether originated fromEucalyptus polybractea, by cytochrome P450 3A enzymes in rat and human liver microsomes. Drug Metab. Dispos. 29 (2001) 200-205. [PMID: 11159812]

2. Hawkes, D.B., Adams, G.W., Burlingame, A.L., Ortiz de Montellano, P.R. and De Voss, J.J. Cytochrome P450_cin (CYP176A), isolation, expression, and characterization. J. Biol. Chem. 277 (2002) 27725-27732. [PMID: 12016226]

3. Meharenna, Y.T., Li, H., Hawkes, D.B., Pearson, A.G., De Voss, J. and Poulos, T.L. Crystal structure of P450_cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450_cam. Biochemistry 43 (2004) 9487-9494. [PMID: 15260491]

EC 1.14.13.t

Accepted name: linalool 8-monooxygenase

Reaction: (1) linalool + NADH + H⁺ + O₂ = (6E)-8-hydroxylinalool + NAD⁺ + H₂O
(2) (6E)-8-hydroxylinalool + NADH + H⁺ + O₂ = (6E)-8-oxolinalool + NAD⁺ + 2 H₂O

For diagram click here.

Other name(s): P-450lin

Systematic name: linalool,NADH:oxygen oxidoreductase (8-hydroxylating)

Comments: A heme-thiolate protein (P-450). The secondary electron donor is a specific [2Fe-2S] ferredoxin from the same bacterial strain.

Links to other databases: BRENDA, EXPASY, KEGG, ERGO, CAS registry number: 95329-13-8

References:

1. Bhattacharyya, P.K., Samanta, T.B., Ullah, A.H.J. and Gunsalus, I.C. Chemical probes into the active centre of a heme thiolate monoxygenase. Proc. Indian Acad. Sci., Chem. Sci. 93 (1984) 1289-1304.

2. Ullah, A.J., Murray, R.I., Bhattacharyya, P.K., Wagner, G.C. and Gunsalus, I.C. Protein components of a cytochrome P-450 linalool 8-methyl hydroxylase. J. Biol. Chem. 265 (1990) 1345-1351. [PMID: 2295633]

3. Ropp, J.D., Gunsalus, I.C. and Sligar, S.G. Cloning and expression of a member of a new cytochrome P-450 family: cytochrome P-450lin (CYP111) from Pseudomonas incognita. J. Bacteriol. 175 (1993) 6028-6037. [PMID: 8376348]

EC 1.14.13.u

Accepted name: (+)-sabinene 3-hydroxylase

Reaction: (+)-sabinene + NADPH + H⁺ + O₂ = (+)-cis-sabinol + NADP⁺ + H₂O

For diagram click here.

Other name(s):

Systematic name: (+)-sabinene,NADPH:oxygen oxidoreductase (3-hydroxylating)

Comments: A heme-thiolate protein (P-450).

References:

1. Karp, F., Harris, J.L. and Croteau, R. Metabolism of monoterpenes: demonstration of the hydroxylation of (+)-sabinene to (+)-cis-sabinol by an enzyme preparation from sage (Salvia officinalis) leaves. Arch. Biochem. Biophys. 256 (1987) 179-193. [PMID: 3111374]

EC 1.14.13.v

Accepted name: (+)-camphor 6-exo-hydroxylase

Reaction: (+)-camphor + NADPH + H⁺ + O₂ = (+)-6-exo-hydroxycamphor + NADP⁺ + H₂O

For diagram click here.

Other name(s): (+)-camphor 6-hydroxylase

Systematic name: (+)-camphor,NADPH:oxygen oxidoreductase (6-exo-hydroxylating)

Comments: A heme-thiolate protein (P-450).

References:

1. Funk C, Croteau R. Induction and Characterization of a cytochrome P-450-dependent camphor hydroxylase in tissue cultures of common sage (Salvia officinalis). Plant Physiol. 101 (1993) 1231-1237. [PMID: 12231778]

2. Funk C, Koepp AE, Croteau R. Catabolism of camphor in tissue cultures and leaf disks of common sage (Salvia officinalis). Arch. Biochem. Biophys. 294 (1992) 306-313. [PMID: 1550356]

EC 1.14.13.w

Accepted name: geraniol 10-dihydroxylase

Reaction: geraniol + NADPH + H⁺ + O₂ = 8-hydroxygeraniol + NADP⁺ + H₂O

For diagram click here.

Other name(s): G10H; CYP76B6

Systematic name: geraniol,NADPH:oxygen oxidoreductase (10-hydroxylating)

Comments: A heme-thiolate protein (P-450). Also hydroxylates nerol and citronellol, cf. EC 1.14.99.28 linalool 8-monooxygenase. The recommended numbering of geraniol gives 8-hydroxygeraniol as the product rather than 10-hydroxygeraniol as implied by the accepted name. See prenol nomenclature Pr-1.

References:

1. Hallahan, D.L. and West, J.M. Cytochrome P-450 in plant/insect interactions: geraniol 10-hydroxylase and the biosynthesis of iridoid monoterpenoids. Drug Metabol. Drug Interact. 12 (1995) 369-382. [PMID: 8820862]

2. Collu, G., Unver, N., Peltenburg-Looman, A.M., van der Heijden, R., Verpoorte, R. and Memelink, J. Geraniol 10-hydroxylase, a cytochrome P450 enzyme involved in terpenoid indole alkaloid biosynthesis. FEBS Lett. 508 (2001) 215-220. [PMID: 11718718]

3. Canto-Canche, B.B., Meijer, A.H., Collu, G., Verpoorte, R. and Loyola-Vargas, V.M. Characterization of a polyclonal antiserum against the monoterpene monooxygenase, geraniol 10-hydroxylase from Catharanthus roseus. J Plant Physiol. 162 (2005) 393-402. [PMID: 15900881]

EC 1.14.15.x

Accepted name: (+)-camphor 6-endo-hydroxylase

Reaction: (+)-camphor + reduced putidaredoxin + O₂ = (+)-6-endo-hydroxycamphor + oxidized putidaredoxin + H₂O

For diagram click here.

Other name(s): P450_camr

Systematic name: (+)-camphor,reduced putidaredoxin:oxygen oxidoreductase (6-endo-hydroxylating)

Comments: A heme-thiolate protein (P-450).

References:

1. Grogan, G., Roberts, G.A., Parsons, S., Turner, N.J. and Flitsch, S.L. P450(camr), a cytochrome P450 catalysing the stereospecific 6-endo-hydroxylation of (1R)-(+)-camphor. Appl. Microbiol. Biotechnol. 59 (2002) 449-454. [PMID: 12172608]

EC 2.1.1.x

Accepted name: geranyl diphosphate 2-C-methyltransferase

Reaction: S-adenosyl-L-methionine + geranyl diphosphate = S-adenosyl-L-homocysteine + (E)-2-methylgeranyl diphosphate

For diagram click here and mechanism click here.

Other name(s): SCO7701

Systematic name: S-adenosyl-L-methionine:geranyl-diphosphate 2-C-methyltransferase

Comments: This enzyme with EC 4.2.3.mq, 2-methylisoborneol synthase, gives 2-methylisoborneol, a characteristc odour produced by soil microorganisms.

References:

1. Wang, C.M. and Cane, D.E. Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor. J. Am. Chem. Soc. 130 (2008) 8908-8909. [PMID: 18563898]

EC 3.1.1.83

Accepted name: monoterpene ε-lactone hydrolase

Reaction: isoprop(en)ylmethyloxepan-2-one + H₂O = 6-hydroxyisoprop(en)ylmethylhexanoate

For diagram of dihydrocarvone catabolism click here, or menthone catabolism click here.

Other name(s): MLH

Systematic name: methylisoprop(en)yloxepan-2-one lactonohydrolase

Comments: Hydrolyses the ε-lactones produced by a Baeyer-Villiger oxidation of menthan-2(or3)-ones

References:

1. van der Vlugt-Bergmans, C.J. and van der Werf, M.J. Genetic and biochemical characterization of a novel monoterpene ε-lactone hydrolase from Rhodococcus erythropolis DCL14. Appl. Environ. Microbiol. 67 (2001) 733-741. [PMID: 11157238]

EC 3.1.1.83

Accepted name: geranyl diphosphate diphosphatase

Reaction: geranyl diphosphate + H₂O = geraniol + diphosphate

For diagram click here.

Other name(s): geraniol synthase; geranyl pyrophosphate pyrophosphatase; GES; CtGES

Systematic name: geranyl-diphosphate diphosphohydrolase

Comments: Requires Mg²⁺ or Mn²⁺. The mechanism involves a geranyl cation which is hydrated. Neryl diphosphate is hydrolysed more slowly. May be the same as EC 3.1.7.3 monoterpenyl-diphosphatase

References:

1. Iijima, Y., Gang, D.R., Fridman, E., Lewinsohn, E. and Pichersky, E. Characterization of geraniol synthase from the peltate glands of sweet basil. Plant Physiol. 134 (2004) 370-379. [PMID: 14657409]

2. Yang, T., Li, J., Wang, H.X. and Zeng, Y. A geraniol-synthase gene from Cinnamomum tenuipilum. Phytochemistry 66 (2005) 285-293. [PMID: 15680985]

EC 3.3.2.8

Accepted name: limonene-1,2-epoxide hydrolase

Reaction: 1,2-epoxymenth-8-ene + H₂O = menth-8-ene-1,2-diol

For diagram click here.

Glossary: limonene-1,2-epoxide = 1,2-epoxymenth-8-ene

Systematic name: 1,2-epoxymenth-8-ene hydrolase

Comments: Both enantiomers are metabolised. It will also hydrolyse 1-methylcyclohexene oxide, cyclohexene oxide, and indene oxide.

References:

1. Barbirato, F., Verdoes, J.C., de Bont, J.A. and van der Werf, M.J. The Rhodococcus erythropolis DCL14 limonene-1,2-epoxide hydrolase gene encodes an enzyme belonging to a novel class of epoxide hydrolases. FEBS Lett. 438 (1998) 293-296. [PMID: 9827564]

2. van der Werf, M.J., Overkamp, K.M. and de Bont, J.A. Limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis DCL14 belongs to a novel class of epoxide hydrolases. J. Bacteriol. 180 (1998) 5052-5057. [PMID: 9748436]

3. van der Werf, M.J., Swarts, H.J. and de Bont, J.A. Rhodococcus erythropolis DCL14 contains a novel degradation pathway for limonene. Appl. Environ. Microbiol. 65 (1999) 2092-2102. [PMID: 10224006]

EC 3.7.1.x

Accepted name: 6-oxocamphor hydrolase

Reaction: bornane-2,6-dione + H₂O = α-campholinate

For diagram click here and mechanism here.

Other name(s): OCH

Systematic name: bornane-2,6-dione hydrolase

Comments: The bornane ring system is cleaved by a retro-Claisen reaction.

References:

1. Grogan, G., Roberts, G.A., Bougioukou, D., Turner, N.J. and Flitsch, S.L. The desymmetrization of bicyclic β-diketones by an enzymatic retro-Claisen reaction. A new reaction of the crotonase superfamily. J. Biol. Chem. 276 (2001) 12565-12572. [PMID: 11278926]

2. Whittingham, J.L., Turkenburg, J.P., Verma, C.S., Walsh, M.A. and Grogan, G. The 2-Å crystal structure of 6-oxo camphor hydrolase. New structural diversity in the crotonase superfamily. J. Biol. Chem. 278 (2003) 1744-1750. [PMID: 12421807]

3. Leonard, P.M. and Grogan, G. Structure of 6-oxocamphor hydrolase H122A mutant bound to its natural product, (2S,4S)-α-campholinic acid: mutant structure suggests an atypical mode of transition state binding for a crotonase homolog. J. Biol. Chem. 279 (2004) 31312-31317. [PMID: 15138275]

*EC 4.2.3.14

Accepted name: (–)-pinene synthase

Reaction: (1) geranyl diphosphate = (–)-α-pinene + diphosphate
(2) geranyl diphosphate = (–)-β-pinene + diphosphate

For reaction pathway click here.

Glossary entries:
α-pinene: a monoterpenoid
β-pinene: a monoterpenoid

Other name(s): β-geraniolene synthase; (–)-(1S,5S)-pinene synthase; geranyldiphosphate diphosphate lyase (pinene forming); pinene synthase; (–)-pinene cyclase; cyclase II

Systematic name: geranyl-diphosphate diphosphate-lyase (cyclizing, (–)-pinene-forming)

Comments: The recombinant enzyme from the grand fir (Abies grandis) requires Mn²⁺ and K⁺ for activity. Mg²⁺ is essentially ineffective as the divalent metal ion cofactor. A mixture of (–)-α and (–)-β-pinene is produced. The ratio depends on the species. With sage (Salvia officinalis) a 1:1 ratio is formed, and with the grand fir (Abies grandis) a 4:6 ratio. It is often accompanied by some (–)-camphene; see EC 4.2.3.mc [(–)-camphene synthase]. (3S)-Linalyl diphosphate can also be used by the enzyme in preference to (3R)-linalyl diphosphate.

Links to other databases: BRENDA, EXPASY, KEGG, ERGO, CAS registry number: 110637-20-2

References:

1. Gambliel, H. and Croteau, R. Pinene cyclases I and II. Two enzymes from sage (Salvia officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. J Biol Chem. 259 (1984) 740-748. [PMID: 6693393]

2. Croteau, R.B., Wheeler, C.J., Cane, D.E., Ebert, R. and Ha, H.J. Isotopically sensitive branching in the formation of cyclic monoterpenes: proof that (–)-α-pinene and (–)-β-pinene are synthesized by the same monoterpene cyclase via deprotonation of a common intermediate. Biochemistry 26 (1987) 5383-5389. [PMID: 3314988]

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 (–)-pinene and (+)- and (–)-camphene. J. Biol. Chem. 263 (1988) 10063-10071. [PMID: 3392006]

4. Croteau, R. and Satterwhite, D.M. Biosynthesis of monoterpenes. Stereochemical implications of acyclic and monocyclic olefin formation by (+)- and (–)-pinene cyclases from sage. J. Biol. Chem. 264 (1989) 15309-15315. [PMID: 2768265]

5. 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.

6. Lewinsohn, E., Gijzen, M. and Croteau, R. Wound-inducible pinene cyclase from grand fir: purification, characterization, and renaturation after SDS-PAGE. Arch. Biochem. Biophys. 293 (1992) 167-173. [PMID: 1731633]

7. McGeady, P., Pyun, H.J., Coates, R.M. and Croteau, R. Biosynthesis of monoterpenes: inhibition of (+)-pinene and (–)-pinene cyclases by thia and aza analogs of the 4R- and 4S-α-terpinyl carbocation. Arch, Biochem. Biophys. 299 (1992) 63-72. [PMID: 1444453]

8. Arigoni, D., Cane, D.E., Shim, J.H., Croteau, R. and Wagschal, K. Monoterpene cyclization mechanisms and the use of natural abundance deuterium NMR - short cut or primrose path ? Phytochemistry 32 (1993) 623-631.

9. Wagschal, K.C., Pyun, H.J., Coates, R.M. and Croteau, R. Monoterpene biosynthesis: isotope effects associated with bicyclic olefin formation catalyzed by pinene synthases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 477-487. [PMID: 8109978]

10. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

11. 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. [PMID: 9268308]

12. Phillips, M.A., Savage, T.J. and Croteau, R. Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers. Arch. Biochem. Biophys. 372 (1999) 197-204. [PMID: 10562434]

13. McKay, S.A., Hunter, W.L., Godard, K.A., Wang, S.X., Martin, D.M., Bohlmann, J. and Plant, A.L. Insect attack and wounding induce traumatic resin duct development and gene expression of (–)-pinene synthase in Sitka spruce. Plant Physiol. 133 (2003) 368-378. [PMID: 12970502]

14. Hyatt, D.C. and Croteau, R. Mutational analysis of a monoterpene synthase reaction: altered catalysis through directed mutagenesis of (–)-pinene synthase from Abies grandis. Arch. Biochem. Biophys. 439 (2005) 222-233. [PMID: 15978541]

EC 4.2.3.ma

Accepted name: (+)-3-carene synthase

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

For reaction pathway click here and mechanism click here.

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

Other name(s): 3-carene cyclase

Systematic name: geranyl-diphosphate diphosphate-lyase [(+)-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.

Links to other databases: CAS registry number: 141907-25-7

References:

1. T.J. and Croteau, R. Biosynthesis of monoterpenes: regio- and stereochemistry of (+)-3-carene biosynthesis. Arch. Biochem. Biophys. 305 (1993) 581-587. [PMID: 8373196]

2. 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]

3. 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]

4. 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. [PMID: 15310829]

EC 4.2.3.mb

Accepted name: β-ocimene synthase

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

For reaction pathway click here.

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

Other name(s): AtTPS03; ama0a23; LjEbetaOS

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

References:

1. Bohlmann, J., Martin, D., Oldham, N.J. and Gershenzon, J. Terpenoid secondary metabolism in Arabidopsis thaliana: cDNA cloning, characterization, and functional expression of a myrcene/(E)-β-ocimene synthase. Arch. Biochem. Biophys. 375 (2000) 261-269. [PMID: 10700382]

2. 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. [PMID: 12624761]

3. 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. [PMID: 12724546]

4. 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. [PMID: 15310830]

EC 4.2.3.mc

Accepted name: (–)-camphene synthase

Reaction: geranyl diphosphate = (–)-camphene + diphosphate

For reaction pathway click here.

Glossary: (–)-camphene = (1S,4R)-2,2-dimethyl-3-methylenebicyclo[2.2.1]heptane

Other name(s): CS

Systematic name: geranyl-diphosphate diphosphate-lyase [(–)-camphene-forming]

References:

1. 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. [PMID: 10441373]

2. Hyatt, D.C. and Croteau, R. Mutational analysis of a monoterpene synthase reaction: altered catalysis through directed mutagenesis of (–)-pinene synthase from Abies grandis. Arch. Biochem. Biophys. 439 (2005) 222-233. [PMID: 15978541]

EC 4.2.3.md

Accepted name: (+)-sabinene synthase

Reaction: geranyl diphosphate = (+)-sabinene + diphosphate

For reaction pathway 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 [(+)-sabinene-forming]

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. [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. [PMID: 12941302]

EC 4.2.3.me

Accepted name: (–)-sabinene synthase

Reaction: geranyl diphosphate = (–)-sabinene + diphosphate

For reaction pathway click here.

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

Systematic name: geranyl-diphosphate diphosphate-lyase [(–)-sabinene-forming]

References:

1. Adam, K.P. and Croteau, R. Monoterpene biosynthesis in the liverwort Conocephalum conicum: demonstration of sabinene synthase and bornyl diphosphate synthase. Phytochemistry 49 (1998) 475-480. [PMID: 9747540]

EC 4.2.3.mf

Accepted name: (+)-pinene synthase

Reaction: (1) geranyl diphosphate = (+)-α-pinene + diphosphate
(2) geranyl diphosphate = (+)-β-pinene + diphosphate

For reaction pathway click here.

Other name(s): (+)-pinene cyclase; cyclase III

Systematic name: geranyl-diphosphate diphosphate-lyase [(+)-pinene-forming]

Links to other databases: CAS registry number: 110637-21-3

References:

1. Wagschal, K.C., Pyun, H.J., Coates, R.M. and Croteau, R. Monoterpene biosynthesis: isotope effects associated with bicyclic olefin formation catalyzed by pinene synthases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 477-487. [PMID: 8109978]

2. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

EC 4.2.3.mg

Accepted name: (+)-α-pinene synthase

Reaction: geranyl diphosphate = (+)-α-pinene + diphosphate

For reaction pathway click here.

Glossary: (+)-α-pinene = (1R,5S)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Other name(s): (+)-α-pinene cyclase; cyclase I

Systematic name: geranyl-diphosphate diphosphate-lyase [(+)-α-pinene-forming]

Comments: It is often accompanied by some (+)-camphene; cf. EC 4.2.3.mc [(–)-camphene synthase]. Unlike EC 4.2.3.mf, (+)-pinene synthase, (+)-β-pinene is not formed to any extent. (3R)-Linalyl diphosphate can also be used by the enzyme in preference to (3S)-linalyl diphosphate.

References:

1. Gambliel, H. and Croteau, R. Pinene cyclases I and II. Two enzymes from sage (Salvia officinalis) which catalyze stereospecific cyclizations of geranyl pyrophosphate to monoterpene olefins of opposite configuration. J Biol Chem. 259 (1984) 740-748. [PMID: 6693393]

2. Wheeler, C.J. and Croteau, R. Terpene cyclase catalysis in organic solvent/minimal water media: demonstration and optimization of (+)-α-pinene cyclase activity. Arch. Biochem. Biophys. 248 (1986) 429-434. [PMID: 3729428]

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 (–)-pinene and (+)- and (–)-camphene. J. Biol. Chem. 263 (1988) 10063-10071. [PMID: 3392006]

4. Croteau, R., Satterwhite, D.M., Wheeler, C.J. and Felton, N.M. Biosynthesis of monoterpenes. Stereochemistry of the enzymatic cyclizations of geranyl pyrophosphate to (+)-alpha-pinene and (–)-β-pinene. J. Biol. Chem. 264 (1989) 2075-2080. [PMID: 2644252]

5. Croteau, R. and Satterwhite, D.M. Biosynthesis of monoterpenes. Stereochemical implications of acyclic and monocyclic olefin formation by (+)- and (–)-pinene cyclases from sage. J. Biol. Chem. 264 (1989) 15309-15315. [PMID: Tetrahedron 31 (1991) 5933-5944.

7. McGeady, P., Pyun, H.J., Coates, R.M. and Croteau, R. Biosynthesis of monoterpenes: inhibition of (+)-pinene and (–)-pinene cyclases by thia and aza analogs of the 4R- and 4S-α-terpinyl carbocation. Arch, Biochem. Biophys. 299 (1992) 63-72. [PMID: 1444453]

8. Wagschal, K.C., Pyun, H.J., Coates, R.M. and Croteau, R. Monoterpene biosynthesis: isotope effects associated with bicyclic olefin formation catalyzed by pinene synthases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 477-487. [PMID: 8109978]

9. Pyun, H.J., Wagschal, K.C., Jung, D.I., Coates, R.M. and Croteau, R. Stereochemistry of the proton elimination in the formation of (+)- and (–)-α-pinene by monoterpene cyclases from sage (Salvia officinalis). Arch. Biochem. Biophys. 308 (1994) 488-496. [PMID: 8109979]

10. Phillips, M.A., Savage, T.J. and Croteau, R. Monoterpene synthases of loblolly pine (Pinus taeda) produce pinene isomers and enantiomers. Arch. Biochem. Biophys. 372 (1999) 197-204. [PMID: 10562434]

11. Phillips, M.A., Wildung, M.R., Williams, D.C., Hyatt, D.C. and Croteau, R. cDNA isolation, functional expression, and characterization of (+)-α-pinene synthase and (–)-α-pinene synthase from loblolly pine (Pinus taeda): stereocontrol in pinene biosynthesis. Arch. Biochem. Biophys. 411 (2003) 267-276. [PMID: 12623076]

EC 4.2.3.mh

Accepted name: (–)-α-pinene synthase

Reaction: geranyl diphosphate = (–)-α-pinene + diphosphate

For reaction pathway click here.

Glossary: (–)-α-pinene = (1S,5R)-2,6,6-trimethylbicyclo[3.1.1]hept-2-ene

Other name(s): (–)-α-pinene cyclase

Systematic name: geranyl-diphosphate diphosphate-lyase [(–)-α-pinene-forming]

Comments: It is often accompanied by some (–)-camphene; see EC 4.2.3.mc [(–)-camphene synthase]. Unlike EC 4.2.3.14, (–)-pinene synthase, (–)-β-pinene is not formed to any extent.

References:

1. Lu, S., Xu, R., Jia, J.W., Pang, J., Matsuda, S.P. and Chen, X.Y. Cloning and functional characterization of a β-pinene synthase from Artemisia annua that shows a circadian pattern of expression. Plant Physiol. 130 (2002) 477-486. [PMID: 12226526]

2. Huber, D.P., 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. [PMID: 15921711]

EC 4.2.3.mi

Accepted name: (–)-β-pinene synthase

Reaction: geranyl diphosphate = (–)-&betha;-pinene + diphosphate

For reaction pathway click here.

Glossary: (–)-β-pinene = (1S,5S)-6,6-dimethyl-2-methylenebicyclo[3.1.1]hept-2-ene

Other name(s): cyclase IV

Systematic name: geranyl-diphosphate diphosphate-lyase [(–)-β-pinene-forming]

Comments: It is often accompanied by some (–)-camphene; see EC 4.2.3.mc [(–)-camphene synthase]. Unlike EC 4.2.3.14, (–)-pinene synthase, (–)-α-pinene is not formed to any extent. (3S)-Linalyl diphosphate can also be used by the enzyme.

References:

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. [PMID: 7625832]

EC 4.2.3.mj

Accepted name: (–)-α-terpineol synthase

Reaction: geranyl diphosphate + H₂O = (–)-α-terpineol + diphosphate

For reaction pathway click here.

Systematic name: geranyl-diphosphate diphosphate-lyase [(–)-α-terpineol-forming]

Comments: Also forms some 1,8-cineole and traces of other monoterpenoids.

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. [PMID: 15184006]

EC 4.2.3.mk

Accepted name: terpinolene synthase

Reaction: geranyl diphosphate = terpinolene + diphosphate

For reaction pathway click here.

Glossary: terpinolene = 1-methyl-4-(propan-2-ylidene)cyclohexene

Systematic name: geranyl-diphosphate diphosphate-lyase (terpinolene-forming)

Comments: Forms traces of other monoterpenoids.

References:

1. 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. [PMID: 10441373]

2. 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. [PMID: 15921711]

EC 4.2.3.ml

Accepted name: 1,8-cineole synthase

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

For reaction pathway click here.

Glossary: 1,8-cineole = 1,8-epoxymenthane = 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 (1,8-cineole-forming)

Comments: Requires Mn²⁺ or Zn²⁺. Mg²⁺ is less effective. As well as 1,8-cineole some pinene isomers, myrcene and (+)-sabinene are formed. The oxygen atom has been shown to be derived from water. (+)-α-Terpineol is an enzyme bound intermediate in the reaction. Neither it nor its phosphate or diphosphate esters can substitute for geranyl diphosphate. The enzyme will also use (–)-(R)-linalyl diphosphate or neryl diphosphate [2].

Links to other databases: CAS registry number: 110637-19-9

References:

1. Croteau, R. and Karp, F. Biosynthesis of monoterpenes: partial purification and characterization of 1,8-cineole synthetase from Salvia officinalis. Arch. Biochem. Biophys. 179 (1977) 257-265. [PMID: 14592]

2. Croteau, R., Alonso, W.R., Koepp, A.E. and Johnson MA. Biosynthesis of monoterpenes: partial purification, characterization, and mechanism of action of 1,8-cineole synthase. Arch. Biochem. Biophys. 309 (1994) 184-192. [PMID: 8117108]

3. 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. [PMID: 9614092]

4. 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. [PMID: 12941302]

5. 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. [PMID: 15299125]

EC 4.2.3.mm

Accepted name: (–)-β-phellandrene synthase

Reaction: geranyl diphosphate = (–)-β-phellandrene + diphosphate

For reaction pathway click here.

Glossary: (–)-β-phellandrene = (3R)-3-isopropyl-6-methylcyclohexene

Other name(s): phellandrene cyclase

Systematic name: geranyl-diphosphate diphosphate-lyase [(–)-β-phellandrene-forming]

Comments: Requires Mg²⁺. Mn²⁺ is less effective. Some (–)-α-phellandrene also formed. The enzyme will also use (+)-(S)-linalyl diphosphate. The reaction involves a 1,3-hydride shift.

Links to other databases: CAS registry number: 137010-34-5

References:

1. 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.

2. 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. [PMID: 8460944]

3. 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. [PMID: 7625832]

4. 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. [PMID: 10441373]

EC 4.2.3.mn

Accepted name: terpinen-4-ol synthase

Reaction: geranyl diphosphate = terpinen-4-ol + diphosphate

For reaction pathway click here.

Glossary: α-terpinene = 1-isopropyl-4-methylcyclohexa-3-en-1-ol

Systematic name: geranyl-diphosphate diphosphate-lyase (terpinen-4-ol-forming)

References:

1. Shelton, D., Zabaras, D., Chohan, S., Wyllie, S.G., Baverstock, P., Leach, D. and Henry, R. Isolation and partial characterisation of a putative monoterpene synthase from Melaleuca alternifolia. Plant Physiol Biochem. 42 (2004) 875-882. [PMID: 15694281]

EC 4.2.3.mo

Accepted name: α-terpinene synthase

Reaction: geranyl diphosphate = α-terpinene + diphosphate

For reaction pathway click here.

Glossary: α-terpinene = 1-isopropyl-4-methylcyclohexa-1,3-diene

Systematic name: geranyl-diphosphate diphosphate-lyase (α-terpinene-forming)

Comments: Requires Mg²⁺. Mn²⁺ less effective. The enzyme will also use (–)-(R)-linalyl diphosphate. The reaction involves a 1,2-hydride shift.

References:

1. 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. [PMID: 10441373]

EC 4.2.3.mp

Accepted name: γ-terpinene synthase

Reaction: geranyl diphosphate = γ-terpinene + diphosphate

For reaction pathway click here.

Glossary: γ-terpinene = 1-isopropyl-4-methylcyclohexa-1,4-diene

Systematic name: geranyl-diphosphate diphosphate-lyase (γ-terpinene-forming)

Comments: Requires Mg²⁺. Mn²⁺ less effective. The reaction involves a 1,2-hydride shift.

References:

1. 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. [PMID: 10441373]

EC 4.2.3.mq

Accepted name: 2-methylisoborneol synthase

Reaction: (E)-2-methylgeranyl diphosphate = 2-methylisoborneol + diphosphate

For reaction pathway click here and mechanism click here.

Other name(s): sco7700

Systematic name: (E)-2-methylgeranyl-diphosphate diphosphate-lyase (2-methylisoborneol-forming)

Comments: Requires Mg²⁺. Gives 2-methylisoborneol, a characteristc odour produced by soil microorganisms.

References:

1. Wang, C.M. and Cane, D.E. Biochemistry and molecular genetics of the biosynthesis of the earthy odorant methylisoborneol in Streptomyces coelicolor. J. Am. Chem. Soc. 130 (2008) 8908-8909. [PMID: 18563898]

*EC 5.5.1.8 (revised)

Accepted name: (+)-bornyl diphosphate synthase

Reaction: geranyl diphosphate = (+)-bornyl diphosphate

For reaction pathway click here and mechanism here.

Other name(s): bornyl pyrophosphate synthase; bornyl pyrophosphate synthetase; (+)-bornyl pyrophosphate cyclase; bornyl diphosphate synthase; geranyl-diphosphate cyclase (ambiguous)

Systematic name: (+)-bornyl-diphosphate lyase (decyclizing)

Comments: Requires Mg²⁺. In vitro the enzyme will also use (3R)-linalyl diphosphate or more slowly neryl diphosphate. The reaction proceeds via isomeration of geranyl diphosphate to (3R)-linalyl diphosphate. The oxygen and phosphorus directly linked to C-1 of geranyl diphosphate is also linked to C-2 of (+)-bornyl diphosphate.

Links to other databases: BRENDA, EXPASY, KEGG, ERGO, 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. [PMID: 42356]

2. 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]

3. 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]

4. 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]

5. 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. [PMID: 2178556]

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. [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. [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. [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. [PMID: 12941302]

EC 5.5.1.x

Accepted name: (–)-bornyl diphosphate synthase

Reaction: geranyl diphosphate = (–)-bornyl diphosphate

For reaction pathway click here.

Other name(s): bornyl pyrophosphate synthase; bornyl pyrophosphate synthetase; (–)-bornyl pyrophosphate cyclase; bornyl diphosphate synthase; geranyl-diphosphate cyclase (ambiguous)

Systematic name: (–)-bornyl-diphosphate lyase (decyclizing)

Comments: Requires Mg²⁺. In vitro the enzyme will also use (3S)-linalyl diphosphate or more slowly neryl diphosphate. The reaction proceeds via isomeration of geranyl diphosphate to (3S)-linalyl diphosphate. The oxygen and phosphorus directly linked to C-1 of geranyl diphosphate is also linked to C-2 of (–)-bornyl diphosphate. The mechanism is enantiomeric to EC 5.5.1.8 (+)-bornyl diphosphate synthase, (see EC 5.5.1.8 mechanism)

Links to other databases: CAS registry number: 110639-17-3

References:

1. Croteau, R. and Shaskus, J. Biosynthesis of monoterpenes: demonstration of a geranyl pyrophosphate:(–)-bornyl pyrophosphate cyclase in soluble enzyme preparations from tansy (Tanacetum vulgare). Arch. Biochem. Biophys. 236 (1985) 535-543. [PMID: 3970524]

2. 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]

3. 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]

4. 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]

5. 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. [PMID: 2178556]