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

J Agric Food Chem

State Key Laboratory for Quality and Safety of Agro - Products, Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Institute of Biotechnology, Zhejiang University, Hangzhou 310058, China.

Published: June 2025


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Article Abstract

Rice blast, caused by , 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 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.

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http://dx.doi.org/10.1021/acs.jafc.5c03733DOI Listing

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