Solanesyl Diphosphate Synthase: From Discovery to Crop Protection.

The increasing prevalence of herbicide-resistant weed biotypes and concerns regarding pesticide toxicity call for the discovery of new, potent, and environmentally benign pesticides. This process requires the identification of new target enzymes, including solanesyl diphosphate synthase (SPS). SPS catalyzes the production of solanesyl diphosphate, a precursor to plastoquinone and ubiquinone, which are essential for plant growth. Targeting the inhibition of SPS has enabled the identification of chemical compounds with agrochemical potential. Owing to its critical role in plant growth and its potential in pesticide discovery, SPS has attracted increasing research interest, resulting in a growing number of publications. However, a consolidated overview of this critical enzyme is still lacking. This review comprehensively integrates current knowledge on SPS function, catalytic mechanism, and inhibition. We present comparative analyses of SPS sequences from rice, wheat, and maize with those of Arabidopsis isoforms. These analyses reveal highly conserved catalytic motifs such as the first aspartate-rich motif (FARM) and the second aspartate-rich motif (SARM), together with localized divergences in substrate-binding pockets that underpin species-specific ligand interactions. We further show that targeted mutations near the conserved motifs can engineer herbicide tolerance in genetically modified (GM) crops. Finally, we propose strategic directions for the rational design and synthesis of next-generation SPS inhibitors and provide a dual strategy for novel pesticide discovery and engineered crop resilience. Collectively, this review paves the way for the rational development of effective and selective SPS inhibitors.