Scholarlink

<p>Dihydroxyacid dehydratase (DHAD), a key enzyme in branched-chain amino acid synthesis in plants, is a promising yet unexploited herbicide target. Inspired by the natural DHAD inhibitor aspterric acid, we design benzoxazinone derivatives with α-hydroxycarboxylic acid moieties as potential inhibitors and develop an eco-friendly α-C(sp³)-H hydroxylation method for accessing carbonyl compounds. Among the derivatives, 7-fluoro-2-hydroxy-3-oxo-4-propyne-3,4-dihydro-2<i>H</i>-benzo[<i>b</i>][1,4]oxazine-2-carboxylic acid (<b>I-6e)</b> completely inhibits <i>Arabidopsis thaliana</i> germination and suppress six weed species by &gt; 50%, with 100% efficacy against <i>Avena fatua</i> and <i>Setaria viridis</i> at 150 g ai/ha. This broad-spectrum activity and rice crop safety highlight its potential as an herbicide lead compound. Compound <b>I-6e</b> exhibits stronger affinity for DHAD (<i>K</i><sub>d</sub> = 1 µM) than that of the natural substrate (<i>K</i><sub>d</sub> = 5.39 µM). The 2.19 Å cocrystal structure of the <i>At</i>DHAD–<b>I-6e</b> complex reveals a unique binding mechanism, confirming the critical role of the α-hydroxycarboxylic acid scaffold. This study provides a blueprint for rational DHAD inhibitor design.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Substrate-based discovery of α-hydroxycarboxylic acid derivatives as potential herbicides targeting dihydroxyacid dehydratase

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月4日

查看全文
  • Bo He,
  • Yanhao Hu,
  • Dongshan Liu,
  • Xin Zang,
  • Xu He,
  • Wang Chen,
  • Jingfang Yang,
  • Mingfeng Feng,
  • Ping Chen,
  • Lirong Wei,
  • Yu Li,
  • Wei Yan,
  • Jun Li,
  • Zhike Feng,
  • Jiahai Zhou,
  • Yonghao Ye

摘要

Dihydroxyacid dehydratase (DHAD), a key enzyme in branched-chain amino acid synthesis in plants, is a promising yet unexploited herbicide target. Inspired by the natural DHAD inhibitor aspterric acid, we design benzoxazinone derivatives with α-hydroxycarboxylic acid moieties as potential inhibitors and develop an eco-friendly α-C(sp³)-H hydroxylation method for accessing carbonyl compounds. Among the derivatives, 7-fluoro-2-hydroxy-3-oxo-4-propyne-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylic acid (I-6e) completely inhibits Arabidopsis thaliana germination and suppress six weed species by > 50%, with 100% efficacy against Avena fatua and Setaria viridis at 150 g ai/ha. This broad-spectrum activity and rice crop safety highlight its potential as an herbicide lead compound. Compound I-6e exhibits stronger affinity for DHAD (Kd = 1 µM) than that of the natural substrate (Kd = 5.39 µM). The 2.19 Å cocrystal structure of the AtDHAD–I-6e complex reveals a unique binding mechanism, confirming the critical role of the α-hydroxycarboxylic acid scaffold. This study provides a blueprint for rational DHAD inhibitor design.