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醛脱氢酶作为一种潜在的杀菌剂靶标被发现,并对其天然抑制剂进行筛选以对抗 。

Discovery of Aldehyde Dehydrogenase as a Potential Fungicide Target and Screening of its Natural Inhibitors against .

机构信息

State Key Laboratory of North China Crop Improvement and regulation/Hebei Key Laboratory of Plant Physiology and Molecular Pathology, Baoding 071000, China.

College of Plant Protection, Hebei Agricultural University, Baoding 071000, China.

出版信息

J Agric Food Chem. 2024 Sep 4;72(35):19424-19435. doi: 10.1021/acs.jafc.4c05553. Epub 2024 Aug 22.

DOI:10.1021/acs.jafc.4c05553
PMID:39172074
Abstract

is the primary pathogen causing ear rot and stalk rot in corn (). 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 and in 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 and 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.

摘要

是引起玉米穗腐病和茎腐病的主要病原体()。它不仅影响产量,还会产生霉菌毒素,危害人类和动物健康。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靶标。然而,关于其在植物病原真菌中的功能的报道有限。在这项研究中,我们分析了表达水平和基因敲除突变体,发现 中的 ALDH 基因 和 通过影响抗氧化能力在致病性和耐低温胁迫方面发挥重要作用。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。进行了生物活性分析后,确定了三种具有 2-羟基苯并吡喃结构的天然类黄酮化合物。其中,杨梅素表现出最高的生物活性和低毒性。和 生物评价均证实杨梅素靶向 ALDH 并抑制其活性。这些发现表明醛脱氢酶可能成为新型杀菌剂设计的有前途的靶标。

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