Transcriptomic insights into the interplay between polyketide biosynthesis and other secondary metabolite biosynthetic clusters and biological pathways in entomopathogen .

Background And Aims: The polyketide synthase gene plays a critical role in insect virulence and cell wall formation in the entomopathogenic fungus . Metabolomics studies have also shown that this gene exhibits crosstalk with other biosynthetic clusters of beauvericins, bassianolide, enniatin A, and ferricrocin. Here, we investigated the cross-pathway communication of biosynthetic cluster and other secondary metabolite clusters and biological pathways using transcriptomes.

Methods: Two comparative transcriptomic analyses were conducted, one compared the wild-type -injected beet armyworm (WT ) with Δ mutant-injected beet armyworm (Δ), and the other one compared WT with wild-type grown . Insect inoculation was performed by intrahemocoelic injection of conidia, hence bypassing the cuticular penetration.

Results: The transcriptomic profile of Δ revealed significant downregulation of genes involved in mycotoxin production, secondary metabolite biosynthesis, and cell wall integrity compared to the WT . Notably, 36 out of 45 secondary metabolite biosynthetic clusters in BCC 2660, were downregulated in Δ, suggesting marked changes in the biosynthesis of secondary metabolites after deletion. These clusters included genes encoding nonribosomal peptide synthetase, transporters, glycosylation, proteolysis, peptidase activity, signal peptides, and cell wall and surface proteins. Our findings indicate that plays an important role in fungal development and pathogenicity. Within the cluster, the UDP-glucosyl transferase gene was consistently upregulated 3-fold in the WT compared to the WT armyworm group 48-96 h post-inoculation. In contrast, was downregulated in Δ compared to the WT during the same period. This regulation pattern suggests that plays a role in the production or modification of secondary metabolites, specifically during the host infection.

Conclusion: This study provides the first transcriptomic evidence that the cluster regulates multiple secondary metabolite clusters, including bassianolide, siderophores, tenellin, oosporein, and several unidentified PKS and NRPS clusters. Additionally, is associated with fungal cell wall remodeling and immune evasion. Our work uncovers an expanded regulatory role for PKS15, revealing novel connection between metabolite biosynthesis and virulence-associated processes, and offering opportunities for targets for biocontrol improvement and metabolite engineering.