Design of Acetohydroxyacid Synthase Herbicide-Resistant Germplasm through MB-QSAR and CRISPR/Cas9-Mediated Base-Editing Approaches

Abstract

The development of herbicide-resistant germplasm is significant in solving the increasingly severe weed problem in crop fields. In this study, we, for the first time, rationally designed a predictable and effective approach to create herbicide-resistant germplasm by combining mutation-dependent biomacromolecular quantitative structure–activity relationship (MB-QSAR) and CRISPR/Cas9-mediated base-editing strategies. Our results showed that the homozygous P197F-G654D-G655S or P197F-G654N-G655S Arabidopsis plants exhibited high resistance to multiple acetohydroxyacid synthase-inhibiting herbicides, including chlorsulfuron, bispyribac-sodium, and flucarbazone-sodium. Additionally, the plants with the homozygous P197S mutant displayed increased susceptibility to bispyribac-sodium than the wild-type but more resistance to flumetsulam than other mutants. Besides, we found that the herbicide resistance levels of the gene-edited plants have a good correlation with MB-QSAR prediction.

Structural basis of resistance to herbicides that target acetohydroxyacid synthase

“…All together, these studies have been successful in expanding the chemical space of inhibitors that can target AHAS resistance mutants. Amongst the most promising leads, there is a series of pyrimidine−biphenyl hybrids that show good herbicidal activity against AHAS inhibitor-resistant Descurainia sophia and Ammannia arenaria 19 . MB-QSAR (Mutation-dependent Biomacromolecular Quantitative Structure-Activity Relationships) is also a promising strategy for the discovery of new herbicides that could be effective against the on-set of resistance 18 , 20 .…”