Apicidin is a key virulence determinant of Fusarium asiaticum in wheat-rice cropping systems.

Apicidin, an emerging mycotoxin with potent histone deacetylase inhibitory and cytotoxic activities, is increasingly detected in wheat and rice in Jiangsu Province, China. Through a population-level screening, we identified a subset of Fusarium asiaticum strains, the dominant pathogen in wheat-rice rotation regions, as the primary producers of apicidin. Using telomere-to-telomere genome assemblies, we identified a biosynthetic gene cluster of 12 genes (FaAps-BGC) essential for apicidin production. Comparative genomic and phylogenomic analyses revealed a complex evolutionary history of FaAps-BGC, characterized by a discontinuous distribution across Fusarium species and extensive structural variation. Large-scale population genome sequencing further showed that loss of apicidin production was associated with either deletion of the entire FaAps-BGC or pseudogenization of the non-ribosomal peptide synthetase (NRPS) backbone gene, and correlated with reduced virulence in both wheat and rice. Functional analyses showed that deletion of the pathway-specific transcription factor gene FaAps2 led to coordinated silencing of other Aps genes within the FaAps-BGC, abolished apicidin biosynthesis, and significantly reduced virulence on both wheat and rice. Mechanistically, apicidin promotes infection by disrupting host plasma membrane integrity, inducing reactive oxygen species (ROS) accumulation, and compromising host defense response in a host-dependent manner. Together, these findings establish apicidin as a key virulence determinant in F. asiaticum and highlight how genomic variation in secondary metabolite biosynthetic pathways shapes fungal virulence in cereal cropping systems.