This supports that the influence of lactate in combination with starch on FB2 production is regulatory rather than an effect solely driven by abundance of precursors. We hypothesise that the FB2 production, when induced, could be regulated globally according to the nutrient/energy state. As a central compound in metabolism, carefully regulated and compartmentalised, Caspase cleavage acetyl-CoA may be a candidate for this [53]. Acetyl-CoA

has been shown to be able to affect transcription in vitro [54]. In yeast, it has been suggested that transcription of the inositol 1-phosphate synthase gene, ino1, is influenced by the acetyl-CoA level during conditions with high levels of CT99021 energy-rich metabolites [55]. In accordance,

we identified a putative inositol-1-phosphate synthase [UniProt: A2QV05] among the proteins with higher levels on SL medium (cl. 35). Inositol-1-phosphate synthase is the first and rate-controlling enzyme in the inositol PD0332991 cost biosynthesis pathway and converts glucose 6-phosphate into inositol 1-phosphate. Inositol is incorporated into phosphatidylinositol that in turn is a precursor of sphingolipids and inositol polyphosphates, required for a diverse set of processes that include glycolipid anchoring of proteins, signal transduction (regulation of chromatin remodeling and transcription), mRNAexport and vesicle trafficking [56, 57]. Acetyl-CoA is also a substrate for protein acetylation by protein acetylases, and acetylation can influence both gene expression and protein activity [58]. In A. parasiticus there has been observed a correlation between initiation and spread of histone acetylation in the aflatoxin gene promoters and the

initiation of aflatoxin gene expression [59]. Another study of A. nidulans has shown that genetic deletion of a histone CYTH4 deacetylase caused elevated gene expression and enhanced production of sterigmatocystin and penicillin [60]. The same study demonstrated that treatment with histone deacetylase inhibitors could enhance production of some secondary metabolites by Penicillium expansum and Alternaria alternata, indicating that histone acetylation and deacetylation have a role in regulation of secondary metabolite production in a broad range of fungal genera. Secondary metabolite synthesis can be subject to multiple regulatory mechanisms. Regulation of fumonisin B1 biosynthesis in F. verticillioides has been found to be complex with several positive and negative regulators and influenced by nitrogen, carbon and pH [12, 61]. Corresponding to our results, fumonisin B1 production in F. verticillioides has been shown to be induced by the presence of starch [62]. However, F. verticillioides and A.