Epigenetic modification in fungi: New metabolites via histone deacetylase inhibition in Chalara sp.

In the last 30 years over 50% of FDA approved drugs were natural products, derivatives, or mimetics of natural products. Among microbial resources, endophytes represent an underexplored source of natural products diversity with a greater discovery rate of novel compounds than their terrestrial counter parts. Under standard laboratory conditions, many natural product biosynthetic gene clusters remain dormant in microorganisms and the fungal endophytes we study are no exemption. Endophyte Chalara sp. 6661 was isolated from Artemisia vulgaris and produces structurally unique antibiotics named isofusidienols. Interestingly, its metabolic profile changed depending on oxygen influx into the culture broth which makes this fungus and ideal candidate for further epigenetic exploration. Herein, isolation of five newly produced compounds from Chalara sp. 6661 under histone deacetylase (HDAC) treatment conditions is described. We used a metabolomics driven approach based on LC-MS data to identify differentiated secondary metabolite production and to guide our isolation efforts. The structures of newly induced secondary metabolites are discussed alongside their biological activity, including extensive testing for cytotoxic, antibiotic and anti-viral activities.