Global regulatory factor FsveA up-regulate the production of antitumor substance in endophytic Fusarium solani

Abstract A number of studies have demonstrated that endophytic fungi have the potential to produce antitumor active substances with novel structures and significant activities. Our previous studies found that an endophytic Fusarium solani derived from the stem of the medicinal plant Nothapodytes pittosporoides (Oliv.) Sleum had good antitumor activity. Furthermore, overexpression of the global regulator FsveA (FsveAOE) in F. solani led to significant inhibition ratio increasement of human alveolar adenocarcino -ma cell (A549). In comparison with the wild strain (WT), the inhibition rate of FsveAOE was obviously increased ~ 14.69%, and the apoptosis ratio was significantly increased 4.86-fold. A metabolomic analysis revealed that the overexpression of FsveA resulted in a significant increasement in several antitumor secondary metabolites of fungi, including alkaloids (Geldanamycin, Acadesine, Adenosine), terpenoids (Lanosterin, Illudin M), carboxylic acid derivatives (L-Arginine, L-Methionine), phenolic (4-Allyl-2-methoxyphenol) and flavonoid metabolites (Epicatechin gallate). Additionally, the transcriptome analysis also displayed that expression pattern of 48 genes-related to the antitumor activity were significantly changed in FsveAOE, mainly involving glycosyl hydrolases, the Zn(2)-Cys(6) class, Cytochrome P450 monooxygen -ase, 3-isopropylmalate dehydratase, and polyketide synthases. Therefore, we conclude that FsveA mediate multiple secondary metabolic pathways to up-regulate the production of antitumor substance in endophytic F. solani.