Natural Product Diversification by One‐Step Biocatalysis using Human P450 3A4

Abstract Efficient synthetic techniques for the diversification of natural products are incremental drug discovery processes pharmaceutical industry because these complex bioactive compounds often require an adjustment properties. Human liver P450 3A4, key player body's detoxification system and decisive factor a drug's metabolic fate, is renowned its broad substrate scope including many products. In this study, we investigated potential human 3A4 product classes isolated produced metabolites six selected at preparative 100‐mg scale. Aided by efficient expression levels in P. pastoris , whole‐cell biocatalyst was found to be highly effective intended job allowing identification total 31 authentic metabolites, them first time. By revealing unprecedented degree diversification, study extends repertoire enzymatic modification one‐step fashion adds completely new view old enzyme traditionally used inhibition toxicology studies.