Overexpression of the global regulator FnVeA upregulates antitumor substances in endophytic Fusarium nematophilum

The special niche of endophytic fungi promotes their potential to produce antitumor compounds with novel structure and significant bioactivity for screening of new antitumor drugs. In our previous studies, we isolated a Fusarium strain from the roots of the medicinal plant Nothapodytes pittosporoides and identified it as Fusarium nematophiium. We found that the crude extract of F. nematophilum had significant antitumor activity on A549 cancer cells, and overexpressing the global regulatory factor FnVeA (the VeA gene of the fungus F. nematophilum) resulted in a significant increase in the antitumor activity, which was approximately fivefold higher than wild strain for relative inhibition rate. In FnVeA(OE), the accumulation of indole, alkene, alkaloid, steroid, and flavonoid metabolites with potential antitumor activity was significantly upregulated compared with wild type via metabolomic analysis. Moreover, the transcriptome analysis showed that 134 differential genes were considered to be closely related to the biosynthesis of antitumor substances, of which 59 differential genes were considered as candidate key genes, and related to tryptophan dimethylallyltransferase, cytochrome P450 monooxygenase, polyketide synthases, and transcription factors. Taken together, we suggest that FnVeA may regulate the biosynthesis of antitumor substances by mediating the expression of genes related to secondary metabolic pathways in F. nematophilum.

Automated summary

Endophytic fungi have the potential to produce antitumor compounds, making them promising sources for screening new antitumor drugs. This study found that a Fusarium strain isolated from a medicinal plant had significant antitumor activity on cancer cells. Overexpressing the regulatory factor FnVeA resulted in a further increase in antitumor activity. Metabolomic analysis revealed upregulation of potential antitumor metabolites in the overexpressing strain. Transcriptome analysis identified key genes involved in the biosynthesis of antitumor substances.