ComQXPA Quorum Sensing Dynamic Regulation Enhanced Fengycin Production of Bacillus subtilis.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-04-25 Epub Date: 2025-03-26 DOI:10.1021/acs.jnatprod.4c01328

Qing Li, Wei Shang, Hui-Zhong Sun, Zheng-Jie Hou, Qiu-Man Xu, Jing-Sheng Cheng

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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 P_srfA 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.

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ComQXPA群体感应动态调控提高枯草芽孢杆菌丰霉素产量

丰霉素是一种抗真菌药物，如果能大量生产，可以作为生物防治剂。ComQXPA群体感应（QS）系统是枯草芽孢杆菌中调节细胞密度依赖性行为的天然机制。本研究利用qs靶向启动子PsrfA在枯草芽孢杆菌中表达pps基因簇，与ComQXPA系统耦合生产风霉素。在昏迷调节蛋白结合位点RE3的突变中，启动子表达强度增加了2.45倍，导致凤霉素产量从489 mg/L增加到1832 mg/L，增加了2.74倍。转录组学分析显示，与碳源吸收和利用相关的基因以及与氨基酸和脂肪酸相关的代谢途径上调，而氨基酸和脂肪酸是凤霉素合成的前体。此外，敲除rapJ和油菜使凤霉素产量增加到3190 mg/L。在与谷氨棒状杆菌共培养体系中，丰霉素产量可达4005 mg/L。本研究为动态调控凤霉素的合成提供了策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

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.