2. Academic Validation
  3. Substrate-based discovery of α-hydroxycarboxylic acid derivatives as potential herbicides targeting dihydroxyacid dehydratase

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

  • Nat Commun. 2025 Jun 4;16(1):5205. doi: 10.1038/s41467-025-60489-8.
Bo He # 1,  Yanhao Hu # 1,  Dongshan Liu # 2,  Xin Zang 2,  Xu He 1,  Wang Chen 1,  Jingfang Yang 3,  Mingfeng Feng 1,  Ping Chen 1,  Lirong Wei 1,  Yu Li 1,  Wei Yan 1,  Jun Li 1,  Zhike Feng 1,  Jiahai Zhou 4 5,  Yonghao Ye 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Agricultural and Forestry Biosecurity, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China.
  • 2 State Key Laboratory of Chemical Biology, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai, 200032, China.
  • 3 State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
  • 4 State Key Laboratory of Chemical Biology, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai, 200032, China. jiahai@nnu.edu.cn.
  • 5 School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, China. jiahai@nnu.edu.cn.
  • 6 State Key Laboratory of Agricultural and Forestry Biosecurity, State & Local Joint Engineering Research Center of Green Pesticide Invention and Application, College of Plant Protection, Nanjing Agricultural University, Nanjing, 210095, China. yeyh@njau.edu.cn.
  • # Contributed equally.
PMID: 40467578 DOI: 10.1038/s41467-025-60489-8
Abstract

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.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z