Harzianic Acid from Trichoderma afroharzianum Is a Natural Product Inhibitor of Acetohydroxyacid Synthase

文献类型： 外文期刊

第一作者： Xie, Linan

作者： Xie, Linan;Cheng, Wei;Chen, Mengbin;Tang, Yi;Xie, Linan;Zang, Xin;Zhou, Jiahai;Cheng, Wei;Zhang, Zhuan;Zhou, Jiahai;Tang, Yi

作者机构：

期刊名称：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY （ 影响因子：15.419； 五年影响因子：15.801 ）

ISSN： 0002-7863

年卷期： 2021 年 143 卷 25 期

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收录情况： SCI

摘要： Acetohydroxyacid synthase (AHAS) is the first enzyme in the branched-chain amino acid biosynthetic pathway and is a validated target for herbicide and fungicide development. Here we report harzianic acid (HA, 1) produced by the biocontrol fungus Trichoderma afroharzianum t-22 (Tht22) as a natural product inhibitor of AHAS. The biosynthetic pathway of HA was elucidated with heterologous reconstitution. Guided by a putative self-resistance enzyme in the genome, HA was biochemically demonstrated to be a selective inhibitor of fungal AHAS, including those from phytopathogenic fungi. In addition, HA can inhibit a common resistant variant of AHAS in which the active site proline is mutated. Structural analysis of AHAS complexed with HA revealed the molecular basis of competitive inhibition, which differs from all known commercial AHAS inhibitors. The alternative binding mode also rationalizes the selectivity of HA, as well as effectiveness toward resistant mutants. A proposed role of HA biosynthesis by Tht22 in the rhizosphere is discussed based on the data.

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