The Enzyme Database

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EC 1.14.13.80      
Transferred entry: (R)-limonene 6-monooxygenase. Now classified as EC 1.14.14.53, (R)-limonene 6-monooxygenase
[EC 1.14.13.80 created 2003, deleted 2017]
 
 
EC 1.14.13.107     
Accepted name: limonene 1,2-monooxygenase
Reaction: (1) (S)-limonene + NAD(P)H + H+ + O2 = 1,2-epoxymenth-8-ene + NAD(P)+ + H2O
(2) (R)-limonene + NAD(P)H + H+ + O2 = 1,2-epoxymenth-8-ene + NAD(P)+ + H2O
For diagram of limonene catabolism, click here
Glossary: limonene = a monoterpenoid
(S)-limonene = (-)-limonene
(R)-limonene = (+)-limonene
limonene-1,2-epoxide = 1,2-epoxymenth-8-ene = 1-methyl-4-(prop-1-en-2-yl)-7-oxabicyclo[4.1.0]heptane
Systematic name: limonene,NAD(P)H:oxygen oxidoreductase
Comments: A flavoprotein (FAD). Limonene is the most widespread terpene and is formed by more than 300 plants. Rhodococcus erythropolis DCL14, a Gram-positive bacterium, is able to grow on both (S)-limonene and (R)-limonene as the sole source of carbon and energy. NADPH can act instead of NADH, although more slowly. It has not been established if the product formed is optically pure or a mixture of two enantiomers.
Links to other databases: BRENDA, EAWAG-BBD, EXPASY, KEGG, MetaCyc, PDB
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 1.14.13.107 created 2009]
 
 
EC 1.14.14.53     
Accepted name: (R)-limonene 6-monooxygenase
Reaction: (R)-limonene + [reduced NADPH—hemoprotein reductase] + O2 = (+)-trans-carveol + [oxidized NADPH—hemoprotein reductase] + H2O
For diagram of carvone biosynthesis, click here
Glossary: limonene = a monoterpenoid
(R)-limonene = (+)-limonene
Other name(s): (+)-limonene-6-hydroxylase; (+)-limonene 6-monooxygenase
Systematic name: (R)-limonene,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (6-hydroxylating)
Comments: The reaction is stereospecific with over 95% yield of (+)-trans-carveol from (R)-limonene. (S)-Limonene, the substrate for EC 1.14.14.51, (S)-limonene 6-monooxygenase, is not a substrate. Forms part of the carvone biosynthesis pathway in Carum carvi (caraway) seeds.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 221461-49-0
References:
1.  Bouwmeester, H.J., Gershenzon, J., Konings, M.C.J.M. and Croteau, R. Biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway. I. Demonstration of enzyme activities and their changes with development. Plant Physiol. 117 (1998) 901–912. [PMID: 9662532]
2.  Bouwmeester, H.J., Konings, M.C.J.M., Gershenzon, J., Karp, F. and Croteau, R. Cytochrome P-450 dependent (+)-limonene-6-hydroxylation in fruits of caraway (Carum carvi). Phytochemistry 50 (1999) 243–248.
[EC 1.14.14.53 created 2003 as EC 1.14.13.80, transferred 2017 to EC 1.14.14.53]
 
 
EC 1.17.99.8     
Accepted name: limonene dehydrogenase
Reaction: (1) (S)-limonene + H2O + acceptor = (–)-perillyl alcohol + reduced acceptor
(2) (R)-limonene + H2O + acceptor = (+)-perillyl alcohol + reduced acceptor
Glossary: limonene = 1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
perillyl alcohol = [4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol
(–)-perillyl alcohol = (S)-perillyl alcohol = [(4S)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol
(+)-perillyl alcohol = (R)-perillyl alcohol = [(4R)-4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol
(–)-limonene = (S)-limonene = (4S)-1-methyl-4-(prop-1-en-2-yl)cyclohexene
(+)-limonene = (R)-limonene = (4R)-1-methyl-4-(prop-1-en-2-yl)cyclohexene
Other name(s): ctmAB (gene names)
Systematic name: limonene:acceptor oxidoreductase (7-hydroxylating)
Comments: Contains FAD. The enzyme, characterized from the bacterium Castellaniella defragrans 65Phen, hydroxylates the R- and S-enantiomers at a similar rate. The in vivo electron acceptor may be a heterodimeric electron transfer flavoprotein (ETF).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc
References:
1.  Petasch, J., Disch, E.M., Markert, S., Becher, D., Schweder, T., Huttel, B., Reinhardt, R. and Harder, J. The oxygen-independent metabolism of cyclic monoterpenes in Castellaniella defragrans 65Phen. BMC Microbiol. 14:164 (2014). [PMID: 24952578]
2.  Puentes-Cala, E., Liebeke, M., Markert, S. and Harder, J. Limonene dehydrogenase hydroxylates the allylic methyl group of cyclic monoterpenes in the anaerobic terpene degradation by Castellaniella defragrans. J. Biol. Chem. 293 (2018) 9520–9529. [PMID: 29716998]
[EC 1.17.99.8 created 2020]
 
 
EC 4.2.3.20     
Accepted name: (R)-limonene synthase
Reaction: geranyl diphosphate = (R)-limonene + diphosphate
For diagram of carvone biosynthesis, click here
Glossary: (R)-limonene = (+)-limonene
Other name(s): (+)-limonene synthase; geranyldiphosphate diphosphate lyase [(+)-(R)-limonene-forming]; geranyl-diphosphate diphosphate-lyase [cyclizing, (+)-(4R)-limonene-forming]
Systematic name: geranyl-diphosphate diphosphate-lyase [cyclizing, (R)-limonene-forming]
Comments: Forms the first step of carvone biosynthesis in caraway. The enzyme from Carum carvi (caraway) seeds requires a divalent metal ion (preferably Mn2+) for catalysis. This enzyme occurs in Citrus, Carum (caraway) and Anethum (dill); (-)-limonene, however, is made in the fir, Abies, and mint, Mentha, by EC 4.2.3.16, (4S)-limonene synthase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 155807-65-1
References:
1.  Bouwmeester, H.J., Gershenzon, J., Konings, M.C.J.M. and Croteau, R. Biosynthesis of the monoterpenes limonene and carvone in the fruit of caraway. I. Demonstration of enzyme activities and their changes with development. Plant Physiol. 117 (1998) 901–912. [PMID: 9662532]
2.  Lücker, J., El Tamer, M.K., Schwab, W., Verstappen, F.W., van der Plas, L.H., Bouwmeester, H.J. and Verhoeven, H.A. Monoterpene biosynthesis in lemon (Citrus limon). cDNA isolation and functional analysis of four monoterpene synthases. Eur. J. Biochem. 269 (2000) 3160–3171. [DOI] [PMID: 12084056]
3.  Maruyama, T., Ito, M., Kiuchi, F. and Honda, G. Molecular cloning, functional expression and characterization of d-limonene synthase from Schizonepeta tenuifolia. Biol. Pharm. Bull. 24 (2001) 373–377. [PMID: 11305598]
[EC 4.2.3.20 created 2003]
 
 
EC 4.2.3.38     
Accepted name: α-bisabolene synthase
Reaction: (2E,6E)-farnesyl diphosphate = (E)-α-bisabolene + diphosphate
For diagram of bisabolene-derived sesquiterpenoid biosynthesis, click here
Other name(s): bisabolene synthase
Systematic name: (2E,6E)-farnesyl-diphosphate diphosphate-lyase [(E)-α-bisabolene-forming]
Comments: This cytosolic sesquiterpenoid synthase requires a divalent cation cofactor (Mg2+ or, to a lesser extent, Mn2+) to neutralize the negative charge of the diphosphate leaving group. While unlikely to encounter geranyl diphosphate (GDP) in vivo as it is localized to plastids, the enzyme can use GDP as a substrate in vitro to produce (+)-(4R)-limonene [cf. EC 4.2.3.20, (R)-limonene synthase]. The enzyme is induced as part of a defense mechanism in the grand fir Abies grandis as a response to stem wounding.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB
References:
1.  Bohlmann, J., Crock, J., Jetter, R. and Croteau, R. Terpenoid-based defenses in conifers: cDNA cloning, characterization, and functional expression of wound-inducible (E)-α-bisabolene synthase from grand fir (Abies grandis). Proc. Natl. Acad. Sci. USA 95 (1998) 6756–6761. [DOI] [PMID: 9618485]
[EC 4.2.3.38 created 2009]
 
 


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