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Proc. Natl. Acad. Sci. USA, Nov 28 2023, 120 (48) e2313197120 | https://doi.org/10.1073/pnas.2313197120
A Novel mechanism of herbicide action through disruption of pyrimidine biosynthesis
Il-Ho Kang 1, Ryan P Emptage 1, Sang-Ic Kim 1, Steven Gutteridge 1
1FMC Agricultural Solutions, Stine Research Center, Newark, DE 19711.
*Corresponding author: correspondence to Steven Gutteridge
Abstract
A lead aryl pyrrolidinone anilide identified using high-throughput in vivo screening was optimized for efficacy, crop safety, and weed spectrum, resulting in tetflupyrolimet. Known modes of action were ruled out through in vitro enzyme and in vivo plant-based assays. Genomic sequencing of aryl pyrrolidinone anilide-resistant
Arabidopsis thaliana progeny combined with nutrient reversal experiments and metabolomic analyses confirmed that the molecular target of the chemistry was dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the fourth step in the de novo pyrimidine biosynthesis pathway. In vitro enzymatic and biophysical assays and a cocrystal structure with purified recombinant plant DHODH further confirmed this enzyme as the target site of this class of chemistry. Like known inhibitors of other DHODH orthologs, these molecules occupy the membrane-adjacent binding site of the electron acceptor ubiquinone. Identification of a new herbicidal chemical scaffold paired with a novel mode of action, the first such finding in over three decades, represents an important leap in combatting weed resistance and feeding a growing worldwide population.
논문정보
- Research article
- 2023년 11월 (BRIC 등록일 2024-02-20)
- 국외 연구진
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