Zheng Qingfei, Fang Hui, Liu Wen
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Org Biomol Chem. 2017 Apr 18;15(16):3376-3390. doi: 10.1039/c7ob00466d.
Thiopeptide antibiotics are a class of typical ribosomally synthesized and post-translationally modified peptides (RiPPs) with complex chemical structures that are difficult to construct via chemical synthesis. To date, more than 100 thiopeptides have been discovered, and most of these compounds exhibit remarkable biological activities, such as antibacterial, antitumor and immunosuppressive activities. Therefore, studies of the biosynthesis of thiopeptides can contribute to the development of new drug leads and facilitate the understanding of the complex post-translational modifications (PTMs) of peptides and/or proteins. Since the biosynthetic gene clusters of thiopeptides were first discovered in 2009, several research studies regarding the biochemistry and enzymology of thiopeptide biosyntheses have been reported, indicating that their characteristic framework is constructed via a cascade of common PTMs and that additional specific PTMs diversify the molecules. In this review, we primarily summarize recent advances in understanding the biosynthesis of thiopeptide antibiotics and propose some potential applications based on our insights into the biosynthetic logic and machinery.
硫肽类抗生素是一类典型的核糖体合成及翻译后修饰肽（RiPPs），其化学结构复杂，难以通过化学合成构建。迄今为止，已发现100多种硫肽，这些化合物大多具有显著的生物活性，如抗菌、抗肿瘤和免疫抑制活性。因此，硫肽生物合成的研究有助于开发新的药物先导物，并促进对肽和/或蛋白质复杂翻译后修饰（PTM）的理解。自2009年首次发现硫肽的生物合成基因簇以来，已有多项关于硫肽生物合成的生物化学和酶学的研究报道，表明其特征性骨架是通过一系列常见的PTM构建的，而额外的特定PTM使分子多样化。在这篇综述中，我们主要总结了在理解硫肽抗生素生物合成方面的最新进展，并基于我们对生物合成逻辑和机制的见解提出了一些潜在应用。
