The demand for discovering novel microbial secondary metabolites is growing to address the limitations in bioactivities such as antibacterial, antifungal, anticancer, anthelmintic, and immunosuppressive functions. Among microbes, the genus Streptomyces holds particular significance for secondary metabolite discovery. Each Streptomyces species typically encodes approximately 30 secondary metabolite biosynthetic gene clusters within its genome, which are mostly uncharacterized in terms of their products and bioactivities. The development of next-generation sequencing has enabled the identification of a large number of potent secondary metabolite biosynthetic gene clusters for novel secondary metabolites that are imbalanced in number compared with discovered secondary metabolites. The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system has revolutionized the translation of enormous genomic potential into the discovery of secondary metabolites as the most efficient genetic engineering tool for Streptomyces. In this review, the current status of CRISPR/Cas applications in Streptomyces is summarized, with particular focus on the identification of secondary metabolite biosynthesis gene clusters and their potential applications.

中文翻译：

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CRISPR辅助基因组工程用于链霉菌次生代谢物生物合成

为了解决抗菌、抗真菌、抗癌、驱虫和免疫抑制功能等生物活性的局限性，对发现新型微生物次级代谢产物的需求不断增长。在微生物中，链霉菌属对于次生代谢物的发现具有特别重要的意义。每个链霉菌属物种在其基因组内通常编码大约 30 个次生代谢物生物合成基因簇，这些基因簇在其产物和生物活性方面大多没有特征。新一代测序的发展使得能够鉴定大量有效的次生代谢物生物合成基因簇，这些基因簇用于与已发现的次生代谢物相比在数量上不平衡的新型次生代谢物。成簇规则间隔短回文重复 (CRISPR)/CRISPR 相关 (Cas) 系统彻底改变了将巨大基因组潜力转化为次级代谢产物发现的过程，成为链霉菌最有效的基因工程工具。本文综述了CRISPR/Cas在链霉菌中的应用现状，特别关注次生代谢物生物合成基因簇的鉴定及其潜在应用。