Marine Metagenome Mining Reveals Lanthipeptides Colwesin A–C, Exhibiting Novel Ring Topology and Anti-inflammatory Activity

IF 3.7 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

ACS Synthetic Biology Pub Date : 2025-04-02 DOI:10.1021/acssynbio.5c0005710.1021/acssynbio.5c00057

Huimei Wang, Xing Zhao, Denghui Li, Liang Meng, Shanshan Liu, Youming Zhang and Liujie Huo*,

{"title":"Marine Metagenome Mining Reveals Lanthipeptides Colwesin A–C, Exhibiting Novel Ring Topology and Anti-inflammatory Activity","authors":"Huimei Wang, Xing Zhao, Denghui Li, Liang Meng, Shanshan Liu, Youming Zhang and Liujie Huo*, ","doi":"10.1021/acssynbio.5c0005710.1021/acssynbio.5c00057","DOIUrl":null,"url":null,"abstract":"Marine natural products are promising sources for drug discovery due to their unique structures and diverse biological activities. The establishment of the Global Marine Microbiome Genome Catalogue (GOMC) has significantly expanded the repository of natural products derived from marine-associated bacteria. In this study, we identified the Class I lanthipeptide biosynthetic gene cluster col from Colwellia_A sp. based on the GOMC database. Through heterologous expression in Escherichia coli and subsequent structural analysis, we characterized three novel lanthipeptides, colwesins A–C, which possess unique cyclic structures characterized by an exceptionally large number of thioether rings. To the best of our knowledge, colwesin C is the first lanthipeptide simultaneously containing locked, nonoverlapped, and nested ring topologies. These findings highlight the robust ring-forming capacity of Class I lanthipeptide synthetases. Colwesins A–C were found to exhibit anti-inflammatory activity in lipopolysaccharide-induced mouse macrophage RAW264.7 cell lines without detectable cytotoxicity. Overall, our results broaden our understanding of the structural diversity of marine-derived lanthipeptides.","PeriodicalId":26,"journal":{"name":"ACS Synthetic Biology","volume":"14 4","pages":"1014–1020 1014–1020"},"PeriodicalIF":3.7000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Synthetic Biology","FirstCategoryId":"99","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acssynbio.5c00057","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}

引用次数: 0

Abstract

Marine natural products are promising sources for drug discovery due to their unique structures and diverse biological activities. The establishment of the Global Marine Microbiome Genome Catalogue (GOMC) has significantly expanded the repository of natural products derived from marine-associated bacteria. In this study, we identified the Class I lanthipeptide biosynthetic gene cluster col from Colwellia_A sp. based on the GOMC database. Through heterologous expression in Escherichia coli and subsequent structural analysis, we characterized three novel lanthipeptides, colwesins A–C, which possess unique cyclic structures characterized by an exceptionally large number of thioether rings. To the best of our knowledge, colwesin C is the first lanthipeptide simultaneously containing locked, nonoverlapped, and nested ring topologies. These findings highlight the robust ring-forming capacity of Class I lanthipeptide synthetases. Colwesins A–C were found to exhibit anti-inflammatory activity in lipopolysaccharide-induced mouse macrophage RAW264.7 cell lines without detectable cytotoxicity. Overall, our results broaden our understanding of the structural diversity of marine-derived lanthipeptides.

Abstract Image

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Synthetic Biology 生物-

CiteScore

8.00

自引率

10.60%

发文量

380

审稿时长

6-12 weeks

期刊介绍： The journal is particularly interested in studies on the design and synthesis of new genetic circuits and gene products; computational methods in the design of systems; and integrative applied approaches to understanding disease and metabolism. Topics may include, but are not limited to: Design and optimization of genetic systems Genetic circuit design and their principles for their organization into programs Computational methods to aid the design of genetic systems Experimental methods to quantify genetic parts, circuits, and metabolic fluxes Genetic parts libraries: their creation, analysis, and ontological representation Protein engineering including computational design Metabolic engineering and cellular manufacturing, including biomass conversion Natural product access, engineering, and production Creative and innovative applications of cellular programming Medical applications, tissue engineering, and the programming of therapeutic cells Minimal cell design and construction Genomics and genome replacement strategies Viral engineering Automated and robotic assembly platforms for synthetic biology DNA synthesis methodologies Metagenomics and synthetic metagenomic analysis Bioinformatics applied to gene discovery, chemoinformatics, and pathway construction Gene optimization Methods for genome-scale measurements of transcription and metabolomics Systems biology and methods to integrate multiple data sources in vitro and cell-free synthetic biology and molecular programming Nucleic acid engineering.