Cytochromes P450 Associated with the Biosyntheses of Ribosomally Synthesized and Post-translationally Modified Peptides

IF 3.8 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Bio & Med Chem Au Pub Date : 2023-07-13 DOI:10.1021/acsbiomedchemau.3c00026

Guannan Zhong*,

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引用次数: 1

Abstract

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.

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细胞色素P450与核糖体合成和翻译后修饰肽的生物合成有关

核糖体合成和翻译后修饰肽（RiPP）是一类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，以及特殊的生物活性，包括抗菌、抗肿瘤和抗病毒。RiPP的生物合成通过核糖体组装的前体肽进行，该前体肽经历各种翻译后修饰以产生成熟肽。细胞色素P450（CYP或P450）单加氧酶是一个含血红素酶的超家族，由于其广泛的底物范围和优异的催化多功能性，它跨越了广泛的次级代谢产物生物合成途径。与大量的RiPP和P450形成对比的是，与P450相关的RiPP生物合成相对有限，它们的大部分功能和时间仍然神秘。在此，本综述旨在概述P450在迄今为止发现的RiPP生物合成中的显著作用，并说明其显著的功能、机制以及剩余的挑战。这将有助于阐明新的P450发现和RiPP生物合成中的特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Bio & Med Chem Au 药物、生物、化学-

CiteScore

4.10

自引率

0.00%

发文量

期刊介绍： ACS Bio & Med Chem Au is a broad scope open access journal which publishes short letters comprehensive articles reviews and perspectives in all aspects of biological and medicinal chemistry. Studies providing fundamental insights or describing novel syntheses as well as clinical or other applications-based work are welcomed.This broad scope includes experimental and theoretical studies on the chemical physical mechanistic and/or structural basis of biological or cell function in all domains of life. It encompasses the fields of chemical biology synthetic biology disease biology cell biology agriculture and food natural products research nucleic acid biology neuroscience structural biology and biophysics.The journal publishes studies that pertain to a broad range of medicinal chemistry including compound design and optimization biological evaluation molecular mechanistic understanding of drug delivery and drug delivery systems imaging agents and pharmacology and translational science of both small and large bioactive molecules. Novel computational cheminformatics and structural studies for the identification (or structure-activity relationship analysis) of bioactive molecules ligands and their targets are also welcome. The journal will consider computational studies applying established computational methods but only in combination with novel and original experimental data (e.g. in cases where new compounds have been designed and tested).Also included in the scope of the journal are articles relating to infectious diseases research on pathogens host-pathogen interactions therapeutics diagnostics vaccines drug-delivery systems and other biomedical technology development pertaining to infectious diseases.