Antimicrobial Metabolites Produced by CCH01 Isolated From the Gut of , Cultivated in the Presence of a Histone Deacetylase Inhibitor.

Three chemical epigenetic modifiers [5-azacytidine, nicotinamide, and suberoylanilide hydroxamic acid (SAHA)] were applied to induce the metabolites of CCH01, a fungus isolated from the gut of . Metabolite profiles of CCH01 were obviously changed by SAHA treatment. Four metabolites (-), including two new natural sclerotioramine derivatives, isochromophilone XIV () and isochromophilone XV (), and two known compounds, sclerotioramine () and (+)-sclerotiorin (), were isolated and purified from CCH01 treated with SAHA. Their structures were determined by spectroscopic analyzes. Anti-phytopathogenic activities of the isolated compounds - were investigated under laboratory conditions, and compound showed broad and important inhibition activities against (IC = 2.1 μg/mL), (IC = 21.0 μg/mL), f. sp. (IC = 40.4 μg/mL), and (IC = 27.8 μg/mL), which were comparable to those of referenced cycloheximide, with IC values of 0.3, 5.0, 12.4, and 15.3 μg/mL, respectively. Ingredients and showed selective and potent activities against with IC values of 29.9 and 9.7 μg/mL, respectively. Furthermore, the antibacterial bioassays showed that compounds and exhibited strong inhibition activities against , with disc diameters of zone of inhibition (ZOI) of 9.1 mm for both compounds, which were a bit weaker than that of referenced gentamycin with a ZOI of 10.8 mm. Additionally, the new metabolite showed a promising activity against (ZOI = 10.5 mm), comparable to that of positive amphotericin B with a ZOI of 23.2 mm. The present results suggest that chemical epigenetic modifier induction was a promising approach to obtaining antimicrobial metabolites encoded by silent biosynthetic genes of .