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Overexpression of the global regulator FnVeA up-regulates antitumor substances in endophytic Fusarium nematophilum.

The special niche of endophytic fungi promotes their potential to produce antitumor compounds with novel structure and significant bio-activity 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 nematophilum. We found that the crude extract of F. nematophilum had significant anti-tumor activity, and overexpressing the global regulatory factor FnVeA resulted in a significant increase in the anti-tumor activity, which was approximately 5-fold higher than wild strain for relative inhibition rate. In FnVeAOE, the accumulation of indole, alkene, alkaloid, steroid and flavonoid metabolites with potential anti-tumor activity were significantly up-regulated as compared with WT via metabolomic analysis. Moreover, the transcriptome analysis showed that 134 differential genes were considered to be closely related to the biosynthesis of anti-tumor substances, of which 59 differential genes were considered as candidate key genes, and related to tryptophan dimethylallyltransferase, cytochrome P450 monooxygenase, polyketide synthases and transcription factor. Taken together, we suggest that FnVeA may regulate the biosynthesis of anti-tumor substances by mediating the expression of genes related to secondary metabolic pathways in F. nematophilum. Key words: Endophytic Fusarium nematophilum; global regulator VeA; anti-tumor; metabolome; transcriptome.