Cytochrome P450 enzymes (P450s) are broadly distributed among living organisms and play crucial roles in natural product biosynthesis, degradation of xenobiotics, steroid biosynthesis, and drug metabolism. P450s are considered as the most versatile biocatalysts in nature because of the vast variety of substrate structures and the types of reactions they catalyze. In particular, P450s can catalyze regio- and stereoselective oxidations of nonactivated C-H bonds in complex organic molecules under mild conditions, making P450s useful biocatalysts in the production of commodity pharmaceuticals, fine or bulk chemicals, bioremediation agents, flavors, and fragrances. Major efforts have been made in engineering improved P450 systems that overcome the inherent limitations of the native enzymes. In this review, we focus on recent progress of different strategies, including protein engineering, redox-partner engineering, substrate engineering, electron source engineering, and P450-mediated metabolic engineering, in efforts to more efficiently produce pharmaceuticals and other chemicals. We also discuss future opportunities for engineering and applications of the P450 systems.

中文翻译：

---

工程细胞色素 P450 酶系统用于生物医学和生物技术应用。


细胞色素P450酶（P450s）广泛分布于生物体中，在天然产物生物合成、外源物质降解、类固醇生物合成和药物代谢中发挥着至关重要的作用。 P450 被认为是自然界中最通用的生物催化剂，因为其底物结构及其催化的反应类型多种多样。特别是，P450 可以在温和条件下催化复杂有机分子中未活化 CH 键的区域选择性和立体选择性氧化，使 P450 成为商品药品、精细或散装化学品、生物修复剂、香料和香料生产中有用的生物催化剂。人们在工程改进 P450 系统方面做出了重大努力，以克服天然酶的固有局限性。在这篇综述中，我们重点关注不同策略的最新进展，包括蛋白质工程、氧化还原伙伴工程、底物工程、电子源工程和 P450 介导的代谢工程，以更有效地生产药物和其他化学品。我们还讨论了 P450 系统的工程和应用的未来机会。