Molecular Mechanism of Fusarium Fungus Inhibition by Phenazine-1-carboxamide

文献类型： 外文期刊

第一作者： Li, Lei

作者： Li, Lei;Yin, Mengyu;Yu, Wei;Zou, Jingpei;Ye, Yonghao;Zhang, Feng;Ran, Tingting;Wang, Weiwu;Zhu, Hong;Li, Linwei;Sun, Hao;Guo, Jingjing

作者机构：

关键词： phenazine-1-carboxamide; histone acetyltransferase Gcn5; inhibition; development; pathogenicity; DON production; Fusarium graminearum

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.7； 五年影响因子：6.0 ）

ISSN： 0021-8561

年卷期： 2024 年

页码：

收录情况： SCI

摘要： Fusarium head blight caused by Fusarium graminearum is a devastating disease in wheat that seriously endangers food security and human health. Previous studies have found that the secondary metabolite phenazine-1-carboxamide produced by biocontrol bacteria inhibited F. graminearum by binding to and inhibiting the activity of histone acetyltransferase Gcn5 (FgGcn5). However, the detailed mechanism of this inhibition remains unknown. Our structural and biochemical studies revealed that phenazine-1-carboxamide (PCN) binds to the histone acetyltransferase (HAT) domain of FgGcn5 at its cosubstrate acetyl-CoA binding site, thus competitively inhibiting the histone acetylation function of the enzyme. Alanine substitution of the residues in the binding site shared by PCN and acetyl-CoA not only decreased the histone acetylation level of the enzyme but also dramatically impacted the development, mycotoxin synthesis, and virulence of the strain. Taken together, our study elucidated a competitive inhibition mechanism of Fusarium fungus by PCN and provided a structural template for designing more potent phenazine-based fungicides.

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