微生物核糖体合成和翻译后修饰肽的基因组挖掘及生物合成

Genome mining and biosynthesis of microbial ribosomally synthesized and post-translationally modified peptides

摘要:

核糖体合成和翻译后修饰肽(ribosomally synthesized and post-translationally modified peptides, RiPPs)是一类由核糖体合成，并经一系列翻译后修饰形成的次级代谢产物。该类化合物结构多样、稳定性强，具有抗菌、抗病毒、抗炎和抗肿瘤等活性，且不易产生耐药性，因此在医药、食品和农业领域具有巨大的应用潜力。微生物基因组中含有大量未表征的RiPPs生物合成基因簇，但很多基因簇需要其产生菌具备特定的培养条件才能合成有活性的产物，或需与其他环境微生物互作才能激活其生物合成，这些基因簇堪称基因组中的“暗物质”。利用合成生物学手段进行异源生物合成是获得新型RiPPs并加以利用的有效途径。本文综述了微生物中RiPPs的多样性、生物功能、基因组挖掘及其异源生物合成策略等方面的最新研究进展，以期为深入认识RiPPs的结构和生物功能，以及开发应用新型微生物天然产物药物和产品提供理论依据。

Abstract:

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a class of secondary metabolites synthesized by the ribosomes of microorganisms and formed through a series of post-translational modifications. They have diverse structures, high stability, and antimicrobial, antiviral, anti-inflammatory or anti-tumor activities. Moreover, they are not prone to generating drug resistance, thus showcasing great potential to be applied in the fields of medicine, food, and agriculture. The genomes of microorganisms harbor a large number of biosynthetic gene clusters for RiPPs, while many of them require the producing strains to be cultivated in specific conditions or to interact with other environmental microorganisms, being the “dark matter” in the genome. Heterologous biosynthesis is an effective means to obtain novel RiPPs and make use of them. This article reviews the recent research progress in the diversity, bioactivity, genomic mining, and heterologous biosynthesis of RiPPs from microorganisms, with the expectation of providing a theoretical basis for a deeper understanding of the molecular structures and functions of RiPPs, as well as for the development and application of novel microbial active metabolites and their producers.