Discovery and Structural Basis of Zoledronic Acid as a Potent SPS-Targeting Herbicide.

Zoledronic acid inhibits Arabidopsis thaliana SPS1 with an IC50 of 2.55 μM, revealing substrate-competitive binding in key weed and crop SPS enzymes.

• Why it matters: Targeting solanesyl diphosphate synthase (SPS) is crucial for developing herbicides that disrupt plastoquinone-9 biosynthesis, yet substrate-competitive inhibitors are rare, limiting herbicide options for agriculture.
• What they did: Researchers used crystal structures of ZOL-bound SPS from Aegilops tauschii and Sorghum bicolor to elucidate the binding mechanism, demonstrating Mg2+-dependent, substrate-competitive inhibition, and tested herbicidal effects on multiple weed species.
• The result: ZOL effectively caused chlorosis, root-growth inhibition, and ROS accumulation in Arabidopsis, showing promise as a novel herbicide targeting SPS, and providing a structural framework for designing new competitive inhibitors.