Bacterial Biosynthetic P450 Enzyme PikCD50N: A Potential Biocatalyst for the Preparation of Human Drug Metabolites

Autor: Xiaohui Liu, Shengying Li, Xingwang Zhang, Jiawei Guo, Wei Zhang, Gang Zhang, Li Ma, Lei Du, Fengwei Li, Fangyuan Cheng, Pradeepraj Durairaj, Dandan Tang, Xiangtian Long
Rok vydání: 2021
Předmět:
Zdroj: The Journal of Organic Chemistry. 86:14563-14571
ISSN: 1520-6904
0022-3263
DOI: 10.1021/acs.joc.1c01407
Popis: 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.
Databáze: OpenAIRE