The MoSR-MoDde1 Regulatory Axis: A Novel Determinant of DMI Sensitivity and a Target for Sustainable Rice Blast Control.

The transcription factor FgSR functions as a central regulator of ergosterol biosynthesis and 14α-demethylation inhibitor (DMI) sensitivity in Fusarium graminearum, with its orthologous proteins being evolutionarily conserved within Sordariomycetes and Leotiomycetes fungi. In this study, we demonstrate that sterol regulators (SRs) differentially modulate DMI sensitivity across these fungal classes through divergent strategies involving key metabolic genes. In Magnaporthe oryzae, MoSR regulates DMI sensitivity through two distinct mechanisms: it directly modulates the transcription of ergosterol biosynthesis genes MoCYP51A and MoCYP51B, and binds to the DRE (DMI-responsive element) motif to regulate MoDde1 (Magnaporthe oryzae DMI detoxification enzyme 1), a gene encoding a cytochrome P450 monooxygenase involved in detoxification. Evolutionary analysis indicates that MoDde1 functions as a Sordariomycetes-specific detoxification factor, capable of enzymatically degrading DMIs. Based on these findings, we developed a small-molecule D1 targeting MoDde1 and engineered rice lines with reduced MoDde1 expression using host-induced gene silencing (HIGS). Both approaches successfully suppressed the enzymatic activity and expression of MoDde1, respectively, demonstrating a promising sustainable strategy for controlling rice blast disease, particularly in conjunction with DMI fungicides.