Biotransformation of the sesquiterpene (+)-valencene by cytochrome P450(cam) and P450(BM-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 P450(cam) from Pseudomonas putida, and of P450(BM-3) from Bacillus megaterium, have been investigated as a potential route to (+)-nootkatone, a ne fragrance. Wild type P450(cam) 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 P450(BM-) 3 and mutants had higher activities ( up to 43 min(-1)) than P450(cam) 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 P450(BM- 3).