Structural Basis of Solanesyl Diphosphate Synthase Inhibition by Rimisoxafen

Abstract

Solanesyl diphosphate synthase (SPS; EC 2.5.1.85), a key enzyme in plastoquinone biosynthesis, has emerged as a promising herbicide target. Rimisoxafen is a bleaching herbicide that inhibits both SPS and phytoene desaturase (PDS), but the mechanism underlying SPS inhibition remains unclear. Here, we show that rimisoxafen inhibits SPS through a noncompetitive mechanism, similar to the commercial SPS inhibitor aclonifen. Rimisoxafen induced bleaching symptoms in Arabidopsis thaliana, strongly inhibited root growth, and triggered pronounced reactive oxygen species (ROS) accumulation in root tips. Structural analysis of the SPS–rimisoxafen complex revealed a dimer-interface binding mode mediated by π–π stacking and hydrogen-bonding interactions. Transcriptomic analyses further identified conserved hypoxia-associated responses, which were more strongly induced by rimisoxafen. These findings uncover the molecular mechanism of SPS inhibition by rimisoxafen and provide a framework for the structure-guided design of SPS-targeting and dual-target herbicides.