Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function.
Cytochromes P450 for natural product biosynthesis in Streptomyces: sequence, structure, and function.
复制标题
DOI：
10.1039/c7np00034k
复制
发表时间：
2017-08-30
影响因子：
11.9
通讯作者：
Shen B
中科院分区：
文献类型：
--
作者：
Rudolf JD;Chang CY;Ma M;Shen B
细胞色素 P450 酶 (P450s) 是自然界中发现的最精致、用途最广泛的生物催化剂之一。除了在人类类固醇生物合成和药物代谢中发挥众所周知的作用外，P450 还在天然产物生物合成途径中发挥着关键作用。天然产物是已知的化学和结构最多样化的小分子，需要大量的 P450 来接受其独特的支架并使其功能化。在这篇综述中，我们调查了链霉菌属（天然产物最多产者之一）中 P450 目前的催化状况，并全面总结了链霉菌中 P450 的功能特征。超过 8500 个 P450 的序列相似性网络揭示了对这些氧依赖性金属酶的序列功能关系的见解。虽然只有约 2.4% 和 <0.4% 的链霉菌 P450 分别得到了功能和结构特征，但对链霉菌 P450 参与天然产物生物合成的研究揭示了它们在自然界中的不同作用，扩展了它们的催化能力，创建了结构和机械范式，并揭示了它们在生物医学和生物技术应用方面的潜力。对这些非凡酶的持续研究无疑将揭示它们真正的化学和生物能力。
Cytochrome 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.