Fusarium verticillioides is the primary pathogen causing ear rot and stalk rot in corn (Zea mays). It not only affects yields but also produces mycotoxins endangering both human and animal health. Aldehyde dehydrogenase (ALDH) is essential for the oxidation of aldehydes in living organisms, making it a potential target for human drug design. However, there are limited reports on its function in plant pathogenic fungus. In this study, we analyzed the expression levels and gene knockout mutants, revealing that ALDH genes FvALDH-43 and FvALDH-96 in F. verticillioides played significant roles in pathogenicity and resistance to low-temperature stress by affecting antioxidant capacity. Virtual screening for natural product inhibitors and molecular docking were performed targeting FvALDH-43 and FvALDH-96. Following the biological activity analysis, three natural flavonoid compounds featuring a 2-hydroxyphenol chromene were identified. Among these, Taxifolin exhibited the highest biological activity and low toxicity. Both in vitro and in vivo biological evaluations confirmed that Taxifolin targeted ALDH and inhibited its activity. These findings indicate that aldehyde dehydrogenase may serve as a promising target for the design of novel fungicides.

中文翻译：

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乙醛脱氢酶作为潜在杀菌靶点的发现及其对轮枝镰刀菌天然抑制剂的筛选


轮枝镰刀菌 ( Fusarium v​​erticillioides ) 是引起玉米穗腐病和茎腐病的主要病原菌。它不仅影响产量，还会产生危害人类和动物健康的霉菌毒素。醛脱氢酶（ALDH）对于生物体中醛的氧化至关重要，使其成为人类药物设计的潜在目标。然而，其在植物病原真菌中的功能报道有限。在本研究中，我们分析了表达水平和基因敲除突变体，揭示了F. verticillioides中的 ALDH 基因FvALDH-43和FvALDH-96通过影响抗氧化能力在致病性和抗低温胁迫方面发挥着重要作用。针对 FvALDH-43 和 FvALDH-96 进行了天然产物抑制剂的虚拟筛选和分子对接。经过生物活性分析，鉴定出三种以 2-羟基苯酚色烯为特征的天然黄酮类化合物。其中，紫杉叶素具有最高的生物活性和较低的毒性。体外和体内生物学评估均证实 Taxifolin 靶向 ALDH 并抑制其活性。这些发现表明乙醛脱氢酶可能作为新型杀菌剂设计的有前景的靶标。