Abstract
Epigenetic agents, histone deacetylase inhibitor (SAHA) and DNA methyltransferase inhibitor (5-Aza), were added to Czapek-Dox medium to trigger the chemical diversity of marine-derived fungus Aspergillus versicolor XS-20090066. By HPLC and 1H NMR analysis, the diversity of fungal secondary metabolites was significantly increased compared with the control. With the aid of MS/MS-based molecular networking, two new nucleoside derivatives, kipukasins K (1) and L (2) were obtained. Meanwhile, the yields of four known nucleoside derivatives were significantly enhanced. In addition, one new bisabolane sesquiterpene, aspergillusene E (7), along with ten known derivatives were also isolated. The structures were elucidated by comprehensive spectroscopic methods of NMR and HRESIMS analysis. Compounds 1 and 7 displayed antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus with the MIC values of 8–16 μg/mL. Our study revealed that the fungus A. versicolor XS-20090066 has been effectively induced by chemical epigenetic manipulation with a combination of SAHA and 5-Aza to produce new metabolites.
Highlights
Marine-derived fungi are prolific sources of structurally novel and biologically potent natural products for drug discovery (Jin et al, 2016; Blunt et al, 2018)
Chemical epigenetic manipulation has been widely applied to marine-derived fungi as a handy and effective method to activate their silent gene clusters to obtain cryptic secondary metabolites (He et al, 2015; Li et al, 2017)
The chemical epigenetic manipulation on A. versicolor XS20090066 was conducted in Czapek-Dox liquid medium by using histone deacetylase inhibitors (SAHA, suberohydroxamic acid (SBHA), nicotinamide, and sodium butyrate) or/and DNA methyltransferase inhibitors
Summary
Marine-derived fungi are prolific sources of structurally novel and biologically potent natural products for drug discovery (Jin et al, 2016; Blunt et al, 2018). Several approaches have been applied to activate the silent biogenetic gene clusters, such as OSMAC, co-culture, gene manipulation and chemical epigenetic methods (Rutledge and Challis, 2015; Keller, 2018). Chemical epigenetic manipulation has been widely applied to marine-derived fungi as a handy and effective method to activate their silent gene clusters to obtain cryptic secondary metabolites (He et al, 2015; Li et al, 2017). This approach has been successful to induce or change the metabolic pathways to yield new secondary metabolites or enhance the production of the given compounds
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