Zhong Guannan
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
Suzhou Research Institute of Shandong University, Suzhou 215123, China.
ACS Bio Med Chem Au. 2023 Jul 13;3(5):371-388. doi: 10.1021/acsbiomedchemau.3c00026. eCollection 2023 Oct 18.
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a class of exponentially increased natural products with characteristic chemical structures, topologies, and biosynthetic mechanisms as well as exceptional bioactivities including antibacteria, antitumors, and antiviruses. The biosynthesis of RiPP proceeds via a ribosomally assembled precursor peptide that undergoes varied post-translational modifications to generate a mature peptide. Cytochrome P450 (CYP or P450) monooxygenases are a superfamily of heme-containing enzymes that span a wide range of secondary metabolite biosynthetic pathways due to their broad substrate scopes and excellent catalytic versatility. In contrast to the enormous quantities of RiPPs and P450s, the P450 associated RiPP biosynthesis is comparatively limited, with most of their functions and timings remaining mysterious. Herein, this Review aims to provide an overview on the striking roles of P450s in RiPP biosyntheses uncovered to date and to illustrate their remarkable functions, mechanisms, as well as remaining challenges. This will shed light on novel P450 discovery and characterizations in RiPP biosyntheses.
核糖体合成及翻译后修饰肽（RiPPs）是一类数量呈指数增长的天然产物，具有独特的化学结构、拓扑结构和生物合成机制，以及包括抗菌、抗肿瘤和抗病毒等在内的特殊生物活性。RiPP的生物合成通过核糖体组装的前体肽进行，该前体肽经过各种翻译后修饰以生成成熟肽。细胞色素P450（CYP或P450）单加氧酶是一类含血红素的酶超家族，由于其广泛的底物范围和出色的催化多功能性，它们参与了广泛的次级代谢物生物合成途径。与大量的RiPPs和P450s相比，与P450相关的RiPP生物合成相对有限，其大多数功能和作用时机仍不清楚。在此，本综述旨在概述迄今为止发现的P450s在RiPP生物合成中的显著作用，并阐述其非凡功能、机制以及尚存的挑战。这将为RiPP生物合成中新型P450的发现和表征提供线索。
