Discovery and Mode-of-Action Characterization of a New Class of Acetolactate Synthase-Inhibiting Herbicides

Herbicides are effective tools to manage weeds and enablefoodproduction and sustainable agriculture. Corteva Agriscience R & Dhas recently discovered new diphenyl-ether compounds displaying excellentpostemergent efficacy on important weed species along with corn safety.Here, we describe the chemistry, biology, biochemistry, and computationalmodeling research that led to the discovery and elucidation of theprimary mode of action for these compounds. The target protein wasfound to be acetolactate synthase (ALS), a key enzyme in the biosynthesisof branched chain amino acids (valine, leucine, and isoleucine). Whileweed resistance evolution to ALS herbicides is widespread, the molecularinteraction of the diphenyl-ether compounds at the active site ofthe ALS enzyme differs significantly from that of some commercialALS inhibitors. The unique biochemical profile of these moleculesalong with their excellent herbicidal activity and corn selectivitymake them a noteworthy development in the pursuit of novel, safe,and sustainable weed control solutions.