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

IF 3.9 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":3.9000,"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

海洋宏基因组挖掘揭示蓝肽Colwesin A-C具有新颖的环状拓扑结构和抗炎活性

海洋天然产物因其独特的结构和多样的生物活性而成为新药开发的重要资源。全球海洋微生物组基因组目录（GOMC）的建立大大扩展了海洋相关细菌的天然产物库。本研究基于GOMC数据库，从Colwellia_A sp.中鉴定出I类硫肽生物合成基因簇col。通过在大肠杆菌中的异源表达和随后的结构分析，我们鉴定了三种新的镧硫肽，colwesins A-C，它们具有独特的环状结构，其特征是异常多的硫醚环。据我们所知，colwesin C是第一个同时包含锁定、不重叠和嵌套环拓扑结构的硫肽。这些发现突出了一类硫肽合成酶强大的成环能力。在脂多糖诱导的小鼠巨噬细胞RAW264.7细胞系中发现Colwesins A-C具有抗炎活性，但未检测到细胞毒性。总的来说，我们的结果拓宽了我们对海洋来源的镧硫肽结构多样性的理解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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.