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.

中文翻译：

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吩嗪-1-甲酰胺抑制镰刀菌的分子机制


禾谷镰刀菌引起的赤霉病是小麦的一种毁灭性病害，严重危害粮食安全和人类健康。此前的研究发现，生防菌产生的次生代谢产物吩嗪-1-甲酰胺通过与组蛋白乙酰转移酶Gcn5（FgGcn5）结合并抑制其活性来抑制禾谷镰刀菌。然而，这种抑制的详细机制仍不清楚。我们的结构和生化研究表明，phenazine-1-carboxamide (PCN) 在其共底物乙酰辅酶 A 结合位点与 FgGcn5 的组蛋白乙酰转移酶 (HAT) 结构域结合，从而竞争性抑制该酶的组蛋白乙酰化功能。 PCN 和乙酰辅酶 A 共有的结合位点残基的丙氨酸取代不仅降低了酶的组蛋白乙酰化水平，而且还显着影响了菌株的发育、霉菌毒素合成和毒力。总之，我们的研究阐明了 PCN 对镰刀菌的竞争性抑制机制，并为设计更有效的吩嗪类杀菌剂提供了结构模板。