FK506 Targets MoFpr1 to Modulate Autophagy and Ubiquitination, Inhibiting the Pathogenicity of Magnaporthe oryzae

Rice blast, caused by Magnaporthe oryzae, is a major threat to global rice production. This study explores the Antifungal potential of the immunosuppressant FK506 and identifies its target protein, MoFpr1 (FK506-binding protein 1B). FK506 inhibited mycelial growth, appressorium formation, and pathogenicity of M. oryzae in an MoFpr1-dependent manner. Mechanistic analyses revealed that FK506 impairs Autophagy and ubiquitination, supported by transcriptomic and metabolomic data. Structural studies using X-ray crystallography and site-directed mutagenesis confirmed the direct interaction between FK506 and MoFpr1, highlighting the importance of residues Gly95 and Ile97. Furthermore, FK506 demonstrated broad-spectrum Antifungal activity against various plant pathogens and effectively controlled rice blast in laboratory, net-chamber, and field trials with minimal phytotoxicity. These findings position FK506 as a promising Antifungal agent and offer insights into its molecular mechanism, suggesting its potential for sustainable plant disease management.