Biotransformation of the sesquiterpene (+)-valencene by cytochrome P450cam and P450BM-3

Abstract

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 fine 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 P450_cam but multiple orientations in P450_BM-3.