Structural basis of resistance to herbicides that target acetohydroxyacid synthase

Acetohydroxyacid synthase (AHAS) is the target for more than 50 commercial herbicides; first applied to crops in the 1980s. Since then, 197 site-of-action resistance isolates have been identified in weeds, with mutations at P197 and W574 the most prevalent. Consequently, AHAS is at risk of not being a useful target for crop protection. To develop new herbicides, a functional understanding to explain the effect these mutations have on activity is required. Here, we show that these mutations can have two effects (i) to reduce binding affinity of the herbicides and (ii) to abolish time-dependent accumulative inhibition, critical to the exceptional effectiveness of this class of herbicide. In the two mutants, conformational changes occur resulting in a loss of accumulative inhibition by most herbicides. However, bispyribac, a bulky herbicide is able to counteract the detrimental effects of these mutations, explaining why no site-of-action resistance has yet been reported for this herbicide. Acetohydroxyacid synthase (AHAS) is the target of more than 50 commercial herbicides, with many site-of-action resistance isolates identified in weeds. Here, the authors report the structural and kinetic characterizations to explain the effect AHAS mutations have on herbicide potency.

Automated summary

Acetohydroxyacid synthase (AHAS) is the target of more than 50 commercial herbicides, with many site-of-action resistance isolates identified in weeds. The mutations at P197 and W574 of AHAS can reduce the binding affinity of herbicides and abolish time-dependent accumulative inhibition. However, the bulky herbicide bispyribac is able to counteract the detrimental effects of these mutations, explaining the absence of site-of-action resistance to this herbicide.