{"title":"Genome Mining Reveals a Carboxyl O-Methyltransferase Gatekeeping the Biosynthetic Divergence of Tryptophan Dimers","authors":"Liang Ma, Zhiwen Liu, Wenjun Zhang, Yiguang Zhu, Liping Zhang, Weiliang Xiong, Xiao-Nian Li, Xinpeng Tian, Changsheng Zhang","doi":"10.1021/acs.orglett.5c01012","DOIUrl":null,"url":null,"abstract":"Bacterial tryptophan dimers comprise a large family of natural products with promising biological activities. Herein, we report the identification of a methyltransferase, SpmM1, which acts as a gatekeeping enzyme to govern the divergent biosynthesis of tryptophan dimers spiroindimicins (SPMs) and indimicins (IDMs) in <i>Streptomyces marincola</i> SCSIO 03032. Bioinformatics, genetic, and biochemical studies revealed that SpmM1-catalyzed carboxyl <i>O</i>-methylation enabled the common precursor of SPMs and IDMs to flux into the spiro-forming pathway to generate SPMs.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"23 1","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.orglett.5c01012","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
Bacterial tryptophan dimers comprise a large family of natural products with promising biological activities. Herein, we report the identification of a methyltransferase, SpmM1, which acts as a gatekeeping enzyme to govern the divergent biosynthesis of tryptophan dimers spiroindimicins (SPMs) and indimicins (IDMs) in Streptomyces marincola SCSIO 03032. Bioinformatics, genetic, and biochemical studies revealed that SpmM1-catalyzed carboxyl O-methylation enabled the common precursor of SPMs and IDMs to flux into the spiro-forming pathway to generate SPMs.
期刊介绍:
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.