Genome-wide exploration of biosynthetic gene clusters and their association with virulence in the entomopathogenic fungus Beauveria

Species of the genus Beauveria are widely used as biological control agents due to their ability to infect and kill a broad range of arthropod pests. Despite their agricultural importance, the genomic diversity underlying virulence and secondary metabolism across the genus remains uncharacterized. In this study, we performed a comprehensive phylogenomic and biosynthetic gene cluster (BGC) analysis of 322 high-quality Beauveria genomes, including one newly sequenced Beauveria bassiana isolate (AS272) obtained from soil in southern Brazil. The genome of AS272 comprises 32.9 Mb with 9,778 predicted genes and high completeness (96.7% BUSCO). Comparative analysis revealed extensive conservation of orthogroups but indicated that the increased gene repertoire of AS272 is primarily associated with the expansion of existing gene families, particularly transporters belonging to the major facilitator superfamily (MFS) and ATP-binding cassette (ABC) families. Phylogenomic reconstruction based on single-copy orthologs resolved major species clades within the genus and identified potential misidentified genomes in public databases. Genome mining using antiSMASH identified 14,160 BGCs across the dataset, with NRPS and PKS clusters dominating the biosynthetic landscape. Clustering with BiG-SCAPE revealed a mixture of highly conserved gene cluster families (GCFs) and numerous lineage-specific clusters, highlighting both evolutionary stability and diversification of secondary metabolism within Beauveria. Notably, B. bassiana lacked strictly conserved core GCFs across all isolates, instead exhibiting a heavy-tailed distribution of cluster frequencies consistent with substantial intraspecific genomic plasticity. Protein-protein interaction network analysis further indicated that several conserved BGCs are embedded within networks enriched for proteins associated with host-pathogen interactions. Together, these findings reveal a dynamic genomic architecture underlying secondary metabolism and pathogenic potential in Beauveria, providing a comparative framework for understanding virulence evolution and identifying candidate pathways for future functional and biotechnological studies.