1. Academic Validation
  2. FK506 Targets MoFpr1 to Modulate Autophagy and Ubiquitination, Inhibiting the Pathogenicity of Magnaporthe oryzae

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

  • J Agric Food Chem. 2025 Jun 18;73(24):14985-15002. doi: 10.1021/acs.jafc.5c03733.
Wen-Hui Zhao 1 Jiong-Yi Yan 1 2 Ke-Xin Xie 1 Xi-Yu Wu 3 Hui Qian 4 Xi-Chun Luo 1 Jian Liao 1 Chun-Yue An 1 Shuang Liang 2 Jian-Ping Lu 5 Irshad Ali Khan 6 Xue-Ming Zhu 2 Fu-Cheng Lin 2 Xiao-Hong Liu 1
Affiliations

Affiliations

  • 1 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.
  • 2 State Key Laboratory for Quality and Safety of Agro - Products, Zhejiang Provincial Key Laboratory of Agricultural Microbiomics, Key Laboratory of Agricultural Microbiome (MARA), Institute of Plant Protection and Microbiology, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China.
  • 3 Xianghu Laboratory, Hangzhou 311231, China.
  • 4 College of Plant Protection, Shandong Agricultural University, Taian 271018, China.
  • 5 College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
  • 6 Department of Agriculture (Plant Pathology), The University of Swabi, Anbar 23561, Khyber Pakhtunkhwa, Pakistan.
Abstract

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.

Keywords

FK506; X-ray crystallography; broad-spectrum antifungal activity; rice blast.

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