Natural Product Echinocandin Derivative S4286 Induces Mitochondrial Dysfunction to Combat Sclerotinia sclerotiorum.

Sclerotinia stem rot (SSR), caused by S. sclerotiorum with an EC50 value of 0.016 μg/mL, exhibited higher antifungal activity than several commercial fungicides, and remained highly effective against carbendazim-resistant strains. Transcriptomics and molecular docking revealed that S4286 potential targets the mitochondrial division protein (Mdp1) with high affinity. Subsequent functional assays indicated that S4286 triggers mitochondrial dysfunction, characterized by structural damage, loss of membrane potential, reactive oxygen species (ROS) burst, and ATP depletion. Our findings reveal a novel mechanism involving mitochondrial dysfunction and highlight S4286 as a promising lead for developing next-generation fungicides to manage resistance.