Abstract:

Cytochromes P450 belong to a large superfamily of hemeproteins, which are widespread in almost all forms of life. P450s are known as “golden catalysts”, and they are mainly involved in the synthesis of endogenous substances, metabolism of xenobiotics, and biosynthesis of natural products in living organisms. P450- catalyzed reactions demonstrate various advantages including wide substrate spectrum, diverse types of catalytic reactions, and high catalytic regio-and stereospecificity, which make them increasingly attractive in drug/toxin metabolism, and engineered product biosynthesis. Among the P450 catalyzed reactions, the introduction of a hydroxyl group at a specific inert C-H bonds under mild conditions makes them highly useful in high value-added fine chemicals biosynthesis. Hereby the mechanism of selective hydroxylation of P450s and related several common types of electron transfer chain system are introduced. The biosynthesis of several natural flavors and fragrances such as limonene oxygenated derivatives, nootkatone, santalol, 4-hydroxyisophorone, and macrocyclic musk, which are catalyzed by single enzyme-catalyzed biotransformation or whole-cell de novo biosynthesis involving protein and metabolic engineering, are reviewed. Finally, the challenges and prospects of their practical applications are discussed.

Key words: cytochromes P450, flavor and fragrance, biosynthesis, protein engineering, metabolic engineering