Jeong Heonjun, Choe YeonU, Nam Jiyoon, Ban Yeon Hee
Department of Intergrative Molecular and Biomedical Science, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
J Microbiol. 2025 Apr;63(4):e2409026. doi: 10.71150/jm.2409026. Epub 2025 Apr 29.
Streptomyces are a crucial source of bioactive secondary metabolites with significant clinical applications. Recent studies of bacterial and metagenome-assembled genomes have revealed that Streptomyces harbors a substantial number of uncharacterized silent secondary metabolite biosynthetic gene clusters (BGCs). These BGCs represent a vast diversity of biosynthetic pathways for natural product synthesis, indicating significant untapped potential for discovering new metabolites. To exploit this potential, genome mining using comprehensive strategies that leverage extensive genomic databases can be conducted. By linking BGCs to their encoded products and integrating genetic manipulation techniques, researchers can greatly enhance the identification of new secondary metabolites with therapeutic relevance. In this context, we present a step-by-step guide for using the antiSMASH pipeline to identify secondary metabolite-coding BGCs within the complete genome of a novel Streptomyces strain. This protocol also outlines gene manipulation methods that can be applied to Streptomyces to activate cryptic clusters of interest and validate the functions of biosynthetic genes. By following these guidelines, researchers can pave the way for discovering and characterizing valuable natural products.
链霉菌是具有重要临床应用价值的生物活性次级代谢产物的关键来源。最近对细菌和宏基因组组装基因组的研究表明，链霉菌含有大量未表征的沉默次级代谢产物生物合成基因簇（BGC）。这些BGC代表了用于天然产物合成的多种多样的生物合成途径，这表明在发现新代谢产物方面存在巨大的未开发潜力。为了挖掘这一潜力，可以采用利用广泛基因组数据库的综合策略进行基因组挖掘。通过将BGC与其编码产物联系起来并整合遗传操作技术，研究人员可以大大提高对具有治疗相关性的新次级代谢产物的鉴定能力。在此背景下，我们提供了一份逐步指南，介绍如何使用antiSMASH管道在一种新型链霉菌菌株的完整基因组中识别次级代谢产物编码BGC。该方案还概述了可应用于链霉菌的基因操作方法，以激活感兴趣的隐秘基因簇并验证生物合成基因的功能。遵循这些指南，研究人员可以为发现和表征有价值的天然产物铺平道路。
