Antimicrobial Metabolites Produced by Penicillium mallochii CCH01 Isolated From the Gut of Ectropis oblique Cultivated in the Presence of a Histone Deacetylase Inhibitor

摘要

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 (IC50 = 2.1 μg/mL), Curvularia clavata (IC50 = 21.0 μg/mL), Fusarium oxysporum f. sp. Mornordica (IC50 = 40.4 μg/mL), and Botryosphaeria dothidea (IC50 = 27.8 μg/mL), which were comparable to those of referenced cycloheximide, with IC50 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 IC50 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.