Host Metabolites Directly Suppress Fusarium Mycotoxin Biosynthesis and Enable Integrated Control of Rice Spikelet Rot Disease

Abstract Rice spikelet rot disease (RSRD) threatens food safety by contaminating grains with diverse mycotoxins. This study revealed a climate-driven shift in pathogen dominance from Alternaria spp. to Fusarium spp., determining associated toxin chemotypes. Untargeted LC–MS metabolomics of wheat infected by Fusarium graminearum (wild-type vs ΔTri5) identified host-derived metabolites, 5-hydroxyindole-3-acetic acid (5-HIAA) and rutin, as key toxin-suppressing candidates. Both compounds strongly inhibited mycotoxin biosynthesis (>95%) with minimal antifungal activity. Mechanistic analyses showed that rutin disrupted toxisome structure, impairing metabolic flux required for deoxynivalenol (DON) production despite active Tri gene expression. Field trials further demonstrated that disease symptom reduction alone does not ensure toxin control. However, combining difenoconazole with rutin effectively decoupled fungal growth from toxigenesis, reducing NIV accumulation by 89.92%. These findings highlight a chemistry-based strategy using plant-derived metabolic inhibitors to mitigate mycotoxin risks in crops.