{"title":"ComQXPA Quorum Sensing Dynamic Regulation Enhanced Fengycin Production of <i>Bacillus subtilis</i>.","authors":"Qing Li, Wei Shang, Hui-Zhong Sun, Zheng-Jie Hou, Qiu-Man Xu, Jing-Sheng Cheng","doi":"10.1021/acs.jnatprod.4c01328","DOIUrl":null,"url":null,"abstract":"<p><p>Fengycin is an antifungal drug that could be used as a biocontrol agent if it could be produced in high amounts. The ComQXPA quorum sensing (QS) system is a natural mechanism, regulating cell density-dependent behaviors in <i>Bacillus subtilis</i>. This study employed the QS-targeted promoter <i>P</i><sub><i>srfA</i></sub> to express the <i>pps</i> gene cluster in <i>B. subtilis</i>, coupling the ComQXPA system to produce fengycin. Mutations in the ComA regulatory protein-binding site RE3 exhibited a 2.45-fold increase in promoter expression intensity and resulted in an elevation of fengycin production from 489 to 1832 mg/L, a 2.74-fold enhancement. Transcriptomic analysis revealed the upregulation of genes associated with carbon source uptake and utilization and metabolic pathways related to amino acids and fatty acids, which are precursors for fengycin synthesis. Additionally, knockout of <i>rapJ</i> and <i>rapE</i> increased fengycin production to 3190 mg/L. In a coculture system constructed with <i>Corynebacterium glutamicum</i>, fengycin production reached 4005 mg/L. This work provides a strategy for dynamically regulating fengycin synthesis.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.4c01328","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Fengycin is an antifungal drug that could be used as a biocontrol agent if it could be produced in high amounts. The ComQXPA quorum sensing (QS) system is a natural mechanism, regulating cell density-dependent behaviors in Bacillus subtilis. This study employed the QS-targeted promoter PsrfA to express the pps gene cluster in B. subtilis, coupling the ComQXPA system to produce fengycin. Mutations in the ComA regulatory protein-binding site RE3 exhibited a 2.45-fold increase in promoter expression intensity and resulted in an elevation of fengycin production from 489 to 1832 mg/L, a 2.74-fold enhancement. Transcriptomic analysis revealed the upregulation of genes associated with carbon source uptake and utilization and metabolic pathways related to amino acids and fatty acids, which are precursors for fengycin synthesis. Additionally, knockout of rapJ and rapE increased fengycin production to 3190 mg/L. In a coculture system constructed with Corynebacterium glutamicum, fengycin production reached 4005 mg/L. This work provides a strategy for dynamically regulating fengycin synthesis.
期刊介绍:
The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.
When new compounds are reported, manuscripts describing their biological activity are much preferred.
Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.