Biotransformation of the sesquiterpene (+)-valencene by cytochrome P450cam and P450BM-3.
The sesquiterpenoids are a large class of naturally occurring compounds with biological functions and desirable properties. Oxidation of the sesquiterpene (+)-valencene by wild type and mutants of P450cam from Pseudomonas putida, and of P450BM-3 from Bacillus megaterium, have been investigated as a potential route to (+)-nootkatone, a fine fragrance. Wild type P450cam did not oxidise (+)-valencene but the mutants showed activities up to 9.8 nmol (nmol P450)(-1) min(-1), with (+)-trans-nootkatol and (+)-nootkatone constituting >85% of the products. Wild type P450BM-3 and mutants had higher activities (up to 43 min(-1)) than P450cam but were much less selective. Of the many products, cis- and trans-(+)-nootkatol, (+)-nootkatone, cis-(+)-valencene-1,10-epoxide, trans-(+)-nootkaton-9-ol, and (+)-nootkatone-13S,14-epoxide were isolated from whole-cell reactions and characterised. The selectivity patterns suggest that (+)-valencene has one binding orientation in P450cam but multiple orientations in P450BM-3.
Sowden
Rebecca J
RJ
Department of Chemistry, Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, UK OX1 3QR.
Yasmin
Samina
S
Rees
Nicholas H
NH
Bell
Stephen G
SG
Wong
Luet-Lok
LL
D001410:Bacillus megaterium / Q000201:enzymology / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001711:Biotransformation; D019475:Camphor 5-Monooxygenase / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D009251:NADPH-Ferrihemoprotein Reductase; D010084:Oxidation-Reduction; D016958:Pseudomonas putida / Q000201:enzymology / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D012717:Sesquiterpenes; D003577:Cytochrome P-450 Enzyme System; C506706:valencene; D006899:Mixed Function Oxygenases; D019475:Camphor 5-Monooxygenase; D009251:NADPH-Ferrihemoprotein Reductase; C052423:flavocytochrome P450 BM3 monoxygenases