Overexpression of Global Regulator LaeA Induced Secondary Metabolite Production in Aspergillus versicolor 0312

This experiment investigated the effect of the global regulator laeA on the secondary metabolites of Aspergillus versicolor. The laeA gene was cloned from Aspergillus versicolor 0312 to introduce pSilent I overexpression vector, and the recombinant plasmid was introduced into Aspergillus versicolor 0312 by PEG guided protoplast transformation. Then, the over-expressing strain 0312-laeA was screened and verified by metabolic level and gene level. A new compound versicolor A (1) was obtained by liquid fermentation of the over-expressing strain, together with four known compounds, acetylapoaranotin (2), acetylaranotin (3), diisobutyl phthalate (4) and ergosterol (5). The structure of the new compound was elucidated by using various spectroscopic techniques inclusive of HRESIMS, 1D- and 2D-NMR data. Compound 1 showed cytotoxicity against MOLT-4 cell lines with IC50 values of 29.6 mu M, while 2 showed significant cytotoxicities against MOLT-4, MCF-7, and CaCo-2 cell lines with IC50 values of 7.8, 19.9, and 15.9 mu M, respectively. The results further supported that laeA is a global regulator that could up-regulate and/or activate cryptic gene clusters to produce new secondary metabolites. This study provides an important basis for exploring the mechanism of laeA gene on the secondary metabolites of Aspergillus versicolor.