Bioconversion of Mono- and Sesquiterpenoids by Recombinant Human Cytochrome P450 Monooxygenases

Cytochrome P450 monooxygenases play an important role in the biosynthesis and metabolism of terpenoids. We explored the potential of recombinant human liver cytochrome P450 monooxygenases CYP1A2, CYP2C9, and CYP3A4, heterologously expressed in Escherichia coli, to convert mono- and sesquiterpenoids to human metabolites. This natural product group is a diverse class of secondary metabolites and includes several industrially and pharmaceutically interesting compounds. Incubation of cedrol with CYP3A4 resulted in a bioconversion of 74% (+/- 8.9%) after 1 h of the unknown metabolites 2-hydroxycedrol and 4-hydroxycedrol, which have been structurally elucidated by (1)H and (13)C NMR and GC-MS. We conclude that recombinant human cytochrome P450 enzymes can be useful tools in a combinatorial biosynthesis strategy for the production of new natural products and for in vitro metabolization studies.