Post-translational modifications involved in the biosynthesis of thiopeptide antibiotics.
Post-translational modifications involved in the biosynthesis of thiopeptide antibiotics.
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DOI：
10.1039/c7ob00466d
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发表时间：
2017-04
影响因子：
3.2
通讯作者：
Qingfei Zheng;H. Fang;Wen Liu
中科院分区：
文献类型：
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作者：
Qingfei Zheng;H. Fang;Wen Liu
硫肽类抗生素是一类典型的核糖体合成和后修饰的肽（RIPPs），具有复杂的化学结构，难以通过化学合成构建。迄今为止，已经发现了100多种硫肽化合物，其中大多数化合物具有显著的生物活性，如抗菌、抗肿瘤和免疫抑制活性。因此，研究硫肽的生物合成可以有助于开发新的药物先导物，并促进对肽和/或蛋白质的复杂翻译后修饰（PTM）的理解。自2009年首次发现硫肽的生物合成基因簇以来，已经报道了关于硫肽生物合成的生物化学和酶学的几项研究，表明它们的特征框架是通过共同的PTM级联构建的，并且额外的特定PTM使分子多样化。本文主要综述了硫肽类抗生素生物合成的最新进展，并基于对生物合成逻辑和机制的认识提出了一些潜在的应用。
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.