文献类型： 外文期刊
作者： Li, Lei 1 ; Ran, Tingting 2 ; Zhu, Hong 3 ; Yin, Mengyu 1 ; Yu, Wei 1 ; Zou, Jingpei 1 ; Li, Linwei 4 ; Ye, Yonghao 1 ; Sun, Hao 5 ; Wang, Weiwu 2 ; Guo, Jingjing 6 ; Zhang, Feng 1 ;
作者机构： 1.Nanjing Agr Univ, Coll Plant Protect, Nanjing 210095, Jiangsu, Peoples R China
2.Nanjing Agr Univ, Coll Life Sci, Nanjing 210095, Jiangsu, Peoples R China
3.Jiangsu Acad Agr Sci, Tech Ctr Publ Testing & Evaluat & Identificat, Nanjing 210014, Jiangsu, Peoples R China
4.Jiangsu Prov & Chinese Acad Sci, Inst Bot, Jiangsu Prov Engn Res Ctr Ecocultivat & High Value, Jiangsu Key Lab Res & Utilizat Plant Resources, Nanjing 210014, Jiangsu, Peoples R China
5.Nanjing Agr Univ, Coll Sci, Nanjing 210095, Jiangsu, Peoples R China
6.Macao Polytech Univ, Fac Appl Sci, Ctr Artificial Intelligence Driven Drug Discovery, Macau 999078, Peoples R China
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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