Abstract
Chemical epigenetic modification on a marine-derived fungus Aspergillus terreus RA2905 using a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), resulted in a significantly changed metabolic profile. A chemical investigation of its ethyl acetate (EtOAc) extract led to the isolation of a racemate of benzyl furanone racemate (±)-1, which further separated chirally as a pair of new enantiomers, (+)- and (−)-asperfuranone (1), together with two new benzyl pyrones, asperpyranones A (2) and B (3). Their structures were elucidated by analysis of the comprehensive spectroscopic data, including one-dimensional (1D) and two-dimensional (2D) NMR, and HRESIMS. The absolute configurations were determined by electronic circular dichroism (ECD) calculation and single-crystal X-ray crystallographic experiment. The structures with benzyl furanone or benzyl pyrone skeletons were discovered from natural products for the first time. Compounds (±)-1, (+)-1, (−)-1, and 2 displayed the antifungal activities against Candida albicans with MIC values of 32, 16, 64, and 64 μg/mL and PTP1B inhibitory activities with the IC50 values of 45.79, 17.32, 35.50, and 42.32 μM, respectively. Compound 2 exhibited antibacterial activity against Pseudomonas aeruginosa with the MIC value of 32 μg/mL.
Highlights
Marine fungi have proven to be a prolific source of structurally novel and biologically active secondary metabolites [1]
The chemical epigenetic manipulation on A. terreus RA2905 was conducted in a starch liquid
The chemical epigenetic manipulation on A. terreus RA2905 was conducted in a starch liquid medium medium with the conditions of 180◦ rpm, 28 °C, for 7 days, cultivated with histone deacetylase with the conditions of 180 rpm, 28 C, for 7 days, cultivated with histone deacetylase inhibitors and inhibitors and DNA methyltransferase inhibitors in different concentrations (1−1000 μM)
Summary
Marine fungi have proven to be a prolific source of structurally novel and biologically active secondary metabolites [1]. The widespread fungi of Aspergillus genus have been extensively investigated for decades due to their chemical diversities and the respected pharmacological activities of secondary metabolites, such as polyketones, xanthones, alkaloids, cyclic peptides, and terpenes [2,3,4]. Chemical epigenetic manipulation has been widely used as an effective and handy approach to turn on the cryptic biosynthetic pathways in Aspergillus species to obtain induced secondary metabolites. Molecules 2020, 25, 3927 manipulation has been widely used as an effective and handy approach to turn on the cryptic. 25, 3927 biosynthetic in Aspergillus species to obtain induced secondary metabolites. Chemical epigenetic manipulation was applied to the marine algicolous fungus Aspergillus terreus
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