{"title":"BGC heteroexpression strategy for production of novel microbial secondary metabolites.","authors":"Yuanyuan Liu, Yuqi Tang, Zhiyang Fu, Wangjie Zhu, Hong Wang, Huawei Zhang","doi":"10.1016/j.ymben.2025.03.018","DOIUrl":null,"url":null,"abstract":"<p><p>Biosynthetic gene clusters (BGCs) in microbial genomes play a crucial role in the biosynthesis of diverse secondary metabolites (SMs) with pharmaceutical potential. However, most BGCs remain silent under conventional conditions, resulting in the frequently repeated discovery of known SMs. Fortunately, in the past two decades, the heterologous expression of BGCs in genetically tractable hosts has emerged as a powerful strategy to awaken microbial metabolic pathways for making novel microbial SMs. In this review, we comprehensively delineated the development and application of this strategy, highlighting various BGC cloning and assembly techniques and their technical characteristics. We also summarized 519 novel SMs from BGC hetero-expression-derived strains and described their occurrence, bioactivity, mode of action, and biosynthetic logic. Lastly, current challenges and future perspectives for developing more efficient BGC hetero-expression strategies were discussed in this review.</p>","PeriodicalId":18483,"journal":{"name":"Metabolic engineering","volume":" ","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolic engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1016/j.ymben.2025.03.018","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Biosynthetic gene clusters (BGCs) in microbial genomes play a crucial role in the biosynthesis of diverse secondary metabolites (SMs) with pharmaceutical potential. However, most BGCs remain silent under conventional conditions, resulting in the frequently repeated discovery of known SMs. Fortunately, in the past two decades, the heterologous expression of BGCs in genetically tractable hosts has emerged as a powerful strategy to awaken microbial metabolic pathways for making novel microbial SMs. In this review, we comprehensively delineated the development and application of this strategy, highlighting various BGC cloning and assembly techniques and their technical characteristics. We also summarized 519 novel SMs from BGC hetero-expression-derived strains and described their occurrence, bioactivity, mode of action, and biosynthetic logic. Lastly, current challenges and future perspectives for developing more efficient BGC hetero-expression strategies were discussed in this review.
期刊介绍：
Metabolic Engineering (MBE) is a journal that focuses on publishing original research papers on the directed modulation of metabolic pathways for metabolite overproduction or the enhancement of cellular properties. It welcomes papers that describe the engineering of native pathways and the synthesis of heterologous pathways to convert microorganisms into microbial cell factories. The journal covers experimental, computational, and modeling approaches for understanding metabolic pathways and manipulating them through genetic, media, or environmental means. Effective exploration of metabolic pathways necessitates the use of molecular biology and biochemistry methods, as well as engineering techniques for modeling and data analysis. MBE serves as a platform for interdisciplinary research in fields such as biochemistry, molecular biology, applied microbiology, cellular physiology, cellular nutrition in health and disease, and biochemical engineering. The journal publishes various types of papers, including original research papers and review papers. It is indexed and abstracted in databases such as Scopus, Embase, EMBiology, Current Contents - Life Sciences and Clinical Medicine, Science Citation Index, PubMed/Medline, CAS and Biotechnology Citation Index.
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