Le-Le Zhu, Qingyu Yang, De-Gao Wang, Luo Niu, Zhuo Pan, Shengying Li, Yue-Zhong Li*, Wei Zhang* and Changsheng Wu*,
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Intriguingly, coralinone exacerbated cellular aggregation of myxobacteria grown in liquid cultures by enhancing the secretion of extracellular matrix, and the 5-methylation is indispensable for the alleged activity. We provided an evolutionary landscape of the <i>corA</i>-associated biosynthetic gene clusters (BGCs) distributed in the myxobacterial realm, revealing the divergent evolution for the diversity-oriented biosynthesis of 5-alkyated pyrazinones. This phylogenetic contextualization provoked us to identify <i>corB</i> located in the proximity of <i>corA</i> as a self-resistance gene. CorB was experimentally verified to be a protease that hydrolyzes extracellular proteins to antagonize the agglutination-inducing effect of coralinone. Overall, we anticipate these findings will provide new insights into the chemical ecology of myxobacteria and lay foundations for the maximal excavation of these largely underexplored resources.</p><p ><i>corA</i> autonomously codes for 5-methylated pyrazinone that promotes secretion of extracellular matrix to induce agglutination of myxobacteria, and <i>corB</i> encoding a protease is the self-resistance gene.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":null,"pages":null},"PeriodicalIF":12.7000,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acscentsci.3c01363","citationCount":"0","resultStr":"{\"title\":\"Deciphering the Biosynthesis and Physiological Function of 5-Methylated Pyrazinones Produced by Myxobacteria\",\"authors\":\"Le-Le Zhu, Qingyu Yang, De-Gao Wang, Luo Niu, Zhuo Pan, Shengying Li, Yue-Zhong Li*, Wei Zhang* and Changsheng Wu*, \",\"doi\":\"10.1021/acscentsci.3c01363\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Myxobacteria are a prolific source of secondary metabolites with sheer chemical complexity, intriguing biosynthetic enzymology, and diverse biological activities. In this study, we report the discovery, biosynthesis, biomimetic total synthesis, physiological function, structure–activity relationship, and self-resistance mechanism of the 5-methylated pyrazinone coralinone from a myxobacterium <i>Corallococcus exiguus</i> SDU70. A single NRPS/PKS gene <i>corA</i> was genetically and biochemically demonstrated to orchestrate coralinone, wherein the integral PKS part is responsible for installing the 5-methyl group. Intriguingly, coralinone exacerbated cellular aggregation of myxobacteria grown in liquid cultures by enhancing the secretion of extracellular matrix, and the 5-methylation is indispensable for the alleged activity. We provided an evolutionary landscape of the <i>corA</i>-associated biosynthetic gene clusters (BGCs) distributed in the myxobacterial realm, revealing the divergent evolution for the diversity-oriented biosynthesis of 5-alkyated pyrazinones. This phylogenetic contextualization provoked us to identify <i>corB</i> located in the proximity of <i>corA</i> as a self-resistance gene. CorB was experimentally verified to be a protease that hydrolyzes extracellular proteins to antagonize the agglutination-inducing effect of coralinone. 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Deciphering the Biosynthesis and Physiological Function of 5-Methylated Pyrazinones Produced by Myxobacteria
Myxobacteria are a prolific source of secondary metabolites with sheer chemical complexity, intriguing biosynthetic enzymology, and diverse biological activities. In this study, we report the discovery, biosynthesis, biomimetic total synthesis, physiological function, structure–activity relationship, and self-resistance mechanism of the 5-methylated pyrazinone coralinone from a myxobacterium Corallococcus exiguus SDU70. A single NRPS/PKS gene corA was genetically and biochemically demonstrated to orchestrate coralinone, wherein the integral PKS part is responsible for installing the 5-methyl group. Intriguingly, coralinone exacerbated cellular aggregation of myxobacteria grown in liquid cultures by enhancing the secretion of extracellular matrix, and the 5-methylation is indispensable for the alleged activity. We provided an evolutionary landscape of the corA-associated biosynthetic gene clusters (BGCs) distributed in the myxobacterial realm, revealing the divergent evolution for the diversity-oriented biosynthesis of 5-alkyated pyrazinones. This phylogenetic contextualization provoked us to identify corB located in the proximity of corA as a self-resistance gene. CorB was experimentally verified to be a protease that hydrolyzes extracellular proteins to antagonize the agglutination-inducing effect of coralinone. Overall, we anticipate these findings will provide new insights into the chemical ecology of myxobacteria and lay foundations for the maximal excavation of these largely underexplored resources.
corA autonomously codes for 5-methylated pyrazinone that promotes secretion of extracellular matrix to induce agglutination of myxobacteria, and corB encoding a protease is the self-resistance gene.
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.