Bergamotane-family sesquiterpenes from histone deacetylase inhibitor modified cultures of the fungicolous fungus Montagnula donacina (Niessl) Wanas., E.B.G. Jones & K.D. Hyde.

Abstract

Epigenetic modification is an effective strategy for uncovering novel metabolites in fungi. In this study, chemical epigenetic manipulation was applied to culture of the fungicolous fungus Montagnula donacina, resulting in significant changes of its specialised metabolite profile. Seventeen undescribed (nor)-bergamotane-type sesquiterpenoids (1-17) were isolated from the culture broth of M. donacina that treated with epigenetic modifier vorinostat. Their structures were established via extensive spectroscopic methods and computational analyses. Compound 1 features a previously undescribed 12-nor-10(9→8)abeo-bergamotane scaffold, postulated to arise via multi-step oxidation and rearrangement reactions from the precursor massarinolin C. All compounds were evaluated for cytotoxicity against the human cancer line HL-60 and for their ability to inhibit nitric oxide production. Compounds 4, 5, and 17 showed moderate inhibition effects on nitric oxide production with inhibition rates of 61.5 %, 24.0 %, and 43.8 % at a concentration of 50 μM, respectively. This study expands the knowledge of bergamotane-type sesquiterpenes and underscores the effectiveness of epigenetic manipulation as a strategy to activate silent biosynthetic pathways and generate novel specialised metabolites in fungi.