Rudolf Jeffrey D, Chang Chin-Yuan, Ma Ming, Shen Ben
Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458, USA.
Nat Prod Rep. 2017 Aug 30;34(9):1141-1172. doi: 10.1039/c7np00034k.
Covering: up to January 2017Cytochrome P450 enzymes (P450s) are some of the most exquisite and versatile biocatalysts found in nature. In addition to their well-known roles in steroid biosynthesis and drug metabolism in humans, P450s are key players in natural product biosynthetic pathways. Natural products, the most chemically and structurally diverse small molecules known, require an extensive collection of P450s to accept and functionalize their unique scaffolds. In this review, we survey the current catalytic landscape of P450s within the Streptomyces genus, one of the most prolific producers of natural products, and comprehensively summarize the functionally characterized P450s from Streptomyces. A sequence similarity network of >8500 P450s revealed insights into the sequence-function relationships of these oxygen-dependent metalloenzymes. Although only ∼2.4% and <0.4% of streptomycete P450s have been functionally and structurally characterized, respectively, the study of streptomycete P450s involved in the biosynthesis of natural products has revealed their diverse roles in nature, expanded their catalytic repertoire, created structural and mechanistic paradigms, and exposed their potential for biomedical and biotechnological applications. Continued study of these remarkable enzymes will undoubtedly expose their true complement of chemical and biological capabilities.
截至2017年1月
细胞色素P450酶（P450s）是自然界中发现的一些最为精巧且多功能的生物催化剂。除了在人类甾体生物合成和药物代谢中广为人知的作用外，P450s还是天然产物生物合成途径中的关键参与者。天然产物是已知化学和结构最为多样的小分子，需要大量的P450s来接纳其独特的骨架并使其功能化。在本综述中，我们考察了链霉菌属（最丰富的天然产物生产者之一）内P450s当前的催化格局，并全面总结了来自链霉菌的功能已得到表征的P450s。一个包含超过8500个P450s的序列相似性网络揭示了这些氧依赖性金属酶的序列-功能关系。尽管分别仅有约2.4%和不到0.4%的链霉菌P450s在功能和结构上得到了表征，但对参与天然产物生物合成的链霉菌P450s的研究揭示了它们在自然界中的多样作用，扩展了它们的催化功能，建立了结构和机制范式，并展现了它们在生物医学和生物技术应用方面的潜力。对这些非凡酶类的持续研究无疑将揭示它们真正的化学和生物学能力。
