Antimicrobial Metabolites Produced by Penicillium mallochii CCH01 Isolated From the Gut of Ectropis oblique, 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 Penicillium mallochii CCH01, a fungus isolated from the gut of Ectropis oblique . Metabolite profiles of P. mallochii CCH01 were obviously changed by SAHA treatment. Four metabolites ( 1 – 4 ), including two new natural sclerotioramine derivatives, isochromophilone XIV ( 1 ) and isochromophilone XV ( 2 ), and two known compounds, sclerotioramine ( 3 ) and (+)-sclerotiorin ( 4 ), were isolated and purified from P. mallochii CCH01 treated with SAHA. Their structures were determined by spectroscopic analyzes. Anti-phytopathogenic activities of the isolated compounds 1 – 4 were investigated under laboratory conditions, and compound 4 showed broad and important inhibition activities against Curvularia lunata (IC 50 = 2.1 μg/mL), Curvularia clavata (IC 50 = 21.0 μg/mL), Fusarium oxysporum f. sp. Mornordica (IC 50 = 40.4 μg/mL), and Botryosphaeria dothidea (IC 50 = 27.8 μg/mL), which were comparable to those of referenced cycloheximide, with IC 50 values of 0.3, 5.0, 12.4, and 15.3 μg/mL, respectively. Ingredients 2 and 3 showed selective and potent activities against Colletotrichum graminicola with IC 50 values of 29.9 and 9.7 μg/mL, respectively. Furthermore, the antibacterial bioassays showed that compounds 3 and 4 exhibited strong inhibition activities against Bacillus subtilis , 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 1 showed a promising activity against Candida albicans (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 P. mallochii .