Natural product guvermectin inhibits guanosine 5′-monophosphate synthetase and confers broad-spectrum antibacterial activity

文献类型： 外文期刊

第一作者： Zhang, Manman

作者： Zhang, Manman;Yang, Chenyu;Li, Shanshan;Zhang, Yanyan;Xiang, Wensheng;Zhang, Manman;Chen, Xujun;Du, Xiangge;Wang, Xiaodan;Zhang, Manman;Chen, Xujun;Du, Xiangge;Wang, Xiaodan;Li, Lei;Liu, Chongxi;Wang, Xiangjing;Xiang, Wensheng;Li, Cheng;Ma, Aifang;Li, Junzhou;Cao, Peng;Yuchi, Zhiguang

作者机构：

关键词： Guvermectin; Bacterial disease; Antibacterial activity; Guanosine 5 ' -monophosphate synthetase; Guanine

期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.2； 五年影响因子：7.8 ）

ISSN： 0141-8130

年卷期： 2024 年 267 卷

页码：

收录情况： SCI

摘要： Bacterial diseases caused substantial yield losses worldwide, with the rise of antibiotic resistance, there is a critical need for alternative antibacterial compounds. Natural products (NPs) from microorganisms have emerged as promising candidates due to their potential as cost-effective and environmentally friendly bactericides. However, the precise mechanisms underlying the antibacterial activity of many NPs, including Guvermectin (GV), remain poorly understood. Here, we sought to explore how GV interacts with Guanosine 5 ' monophosphate synthetase (GMPs), an enzyme crucial in bacterial guanine synthesis. We employed a combination of biochemical and genetic approaches, enzyme activity assays, site-directed mutagenesis, bio-layer interferometry, and molecular docking assays to assess GV's antibacterial activity and its mechanism targeting GMPs. The results showed that GV effectively inhibits GMPs, disrupting bacterial guanine synthesis. This was confirmed through drug-resistant assays and direct enzyme inhibition studies. Bio-layer interferometry assays demonstrated specific binding of GV to GMPs, with dependency on Xanthosine 5 '-monophosphate. Site-directed mutagenesis identified key residues crucial for the GV-GMP interaction. This study elucidates the antibacterial mechanism of GV, highlighting its potential as a biocontrol agent in agriculture. These findings contribute to the development of novel antibacterial agents and underscore the importance of exploring natural products for agricultural disease management.

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