Comparative S-acyl-proteomics reveals post-translational modulation of fungal purine metabolism for Verticillium wilt

Verticillium wilt, caused by the fungus Verticillium dahliae, is a devastating plant disease leading to severe global agricultural losses. Although the interaction between V. dahliae and host plants has been extensively investigated, the role of metabolic regulation in fungal development and pathogenicity remains poorly understood. Fatty acids serve as metabolic substrates for S-acylation, a post-translational modification that modulates protein properties and functions, yet this process has not been characterized in V. dahliae. Here, our systematic analysis revealed that the protein S-acyltransferase VdERF2 is essential for the development and pathogenicity of V. dahliae. Through comparative S-acyl-proteomic analyses, we found that VdERF2-dependent S-acylation is significantly enriched in metabolic pathways, especially purine metabolism. Among the identified substrates, VdHIUH, an enzyme involved in converting uric acid to allantoin in purine metabolism, requires S-acylation for its full function in fungal development and virulence. VdERF2-mediated S-acylation enhances the activity of VdHIUH, thereby reducing uric acid accumulation. Furthermore, allantoin reduces reactive oxygen species elevated by the VdHIUH S-acylation defect, partially alleviating the fungal developmental impairment. Collectively, our findings reveal a critical mechanism by which S-acylation modulates purine metabolism in V. dahliae, providing new insights into the molecular basis of fungal pathogenicity and offering potential targets for improving crop resistance to Verticillium wilt.