Epigenetic modifiers, including DNA methyltransferase (DNMT) or histone deacetylase (HDAC) inhibitors, are useful to induce the expression of otherwise dormant biosynthetic genes under standard laboratory conditions. We isolated several endophytic fungi from the medicinal plant Datura stramonium L., which produces pharmaceutically important tropane alkaloids, including scopolamine and hyoscyamine. Although none of the endophytic fungi produced the tropane alkaloids, supplementation of a DNMT inhibitor, 5-azacytidine, and/or a HDAC inhibitor, suberoylanilide hydroxamic acid, to the culture medium induced the production of mycotoxins, including alternariol, alternariol-5-O-methyl ether, 3'-hydroxyalternariol-5-O-methyl ether, altenusin, tenuazonic acid, and altertoxin II, by the endophytic fungus Alternaria sp. This is the first report of a mycotoxin-producing endophytic fungus from the medicinal plant D. stramonium L. This work demonstrates that treatments with epigenetic modifiers induce the production of mycotoxins, thus providing a useful tool to explore the biosynthetic potential of the microorganisms.
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