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

## TL;DR

Overexpressing the veA gene in a cold-loving fungus activated hidden chemical pathways, leading to new and known compounds.

## Contribution

Overexpression of veA in Aspergillus sydowii activated silent gene clusters, producing a novel polyhydroxy anthraquinone and expanding natural product diversity.

## Key findings

- Overexpression of veA in Aspergillus sydowii MNP-2 led to the discovery of a novel polyhydroxy anthraquinone and nine known metabolites.
- Compounds 1 and 10 were biosynthetically derived from T2PK and NRPS pathways previously silent in the wild-type strain.
- Compound 3 showed weak antifungal activity against Candida albicans, and compound 4 had weak cytotoxicity against HCT116 cells.

## Abstract

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::veA was constructed by overexpressing the global transcription regulator veA in an Arctic-derived strain Aspergillus sydowii MNP-2. Chemical investigation of the mutant OE::veA resulted in the isolation of one novel polyhydroxy anthraquinone (1) together with nine known metabolites (2–10), 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 1 and 10 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 3 had weak inhibitory effect on human pathogen Candida albicans, with a MIC value of 64 ug/mL, and 4 displayed in vitro weak cytotoxic activity against HCT116 cells (IC50 = 44.47 μM). These results indicate that overexpression of veA effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products.