Bacterial Biosynthetic P450 Enzyme PikCD50N: A Potential Biocatalyst for the Preparation of Human Drug Metabolites
Bacterial Biosynthetic P450 Enzyme PikCD50N: A Potential Biocatalyst for the Preparation of Human Drug Metabolites
复制标题
DOI：
10.1021/acs.joc.1c01407
复制
发表时间：
2021-10-18
影响因子：
3.6
通讯作者：
Li，Shengying
中科院分区：
文献类型：
--
作者：
Guo，Jiawei;Li，Fengwei;Li，Shengying
人类药物代谢物是药物相关研究中广泛使用的重要化学物质。然而，通过化学方法获得这些酶衍生的和区域/立体选择性修饰的化合物是复杂的。PikC是一种生物合成P450酶，参与来自委内瑞拉链霉菌的吡克罗霉素生物合成。在这里，我们确定突变体PikCD 50 Ns作为一个潜在的生物催化剂，具有广泛的底物范围，多样化的产品配置文件，和高催化效率，用于制备HDM。值得注意的是，PikCD 50 N可以使用低成本的H2 O2作为直接电子和氧供体来介导药物代谢反应。
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 bacteriumStreptomyces venezuelae. Here, we identify the mutant PikCD50Nas a potential biocatalyst, with a broad substrate scope, diversified product profile, and high catalytic efficiency, for preparation of HDMs. Remarkably, PikCD50Ncan mediate the drug-metabolizing reactions using the low-cost H2O2as a direct electron and oxygen donor.