Bacterial Biosynthetic P450 Enzyme PikC<sub>D50N</sub>: A Potential Biocatalyst for the Preparation of Human Drug Metabolites
Jiawei Guo, Fengwei Li, Fangyuan Cheng, Li Ma, Xiaohui Liu, Pradeepraj Durairaj, Gang Zhang, Dandan Tang, Xiangtian Long, Wei Zhang, Lei Du, Xingwang Zhang, Shengying Li
Abstract
Human drug metabolites (HDMs) are important chemicals widely used in drug-related studies. However, acquiring these enzyme-derived and regio-/stereo-selectively modified compounds through chemical approaches is complicated. PikC is a biosynthetic P450 enzyme involved in pikromycin biosynthesis from the bacterium Streptomyces venezuelae. Here, we identify the mutant PikCD50N as a potential biocatalyst, with a broad substrate scope, diversified product profile, and high catalytic efficiency, for preparation of HDMs. Remarkably, PikCD50N can mediate the drug-metabolizing reactions using the low-cost H2O2 as a direct electron and oxygen donor.