Chemical Investigation of the Global Regulator veA-Overexpressed Mutant of an Arctic Strain Aspergillus sydowii MNP-2

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::<i>veA</i> was constructed by overexpressing the global transcription regulator <i>veA</i> in an Arctic-derived strain <i>Aspergillus sydowii</i> MNP-2. Chemical investigation of the mutant OE::<i>veA</i> resulted in the isolation of one novel polyhydroxy anthraquinone (<b>1</b>) together with nine known metabolites (<b>2</b>-<b>10</b>), which were unambiguously characterized by various spectroscopic methods including 1D and 2D NMR and HR-ESI-MS as well as via comparison with literature data. Biosynthetically, compounds <b>1</b> and <b>10</b> as new arising chemicals were, respectively, formed by type II polyketide synthase (T2PK) and non-ribosomal peptide synthetase (NRPS), which were silent in the wild-type (WT) strain MNP-2. A bioassay showed that only compound <b>3</b> had weak inhibitory effect on human pathogen <i>Candida albicans,</i> with a MIC value of 64 ug/mL, and <b>4</b> displayed in vitro weak cytotoxic activity against HCT116 cells (IC₅₀ = 44.47 μM). These results indicate that overexpression of <i>veA</i> effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products.