AUTHOR=Zhang Shuxiang , Fang Han , Yin Caiping , Wei Chaoling , Hu Jingwei , Zhang Yinglao 

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

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02186

DOI=10.3389/fmicb.2019.02186

ISSN=1664-302X

ABSTRACT=<p>Three chemical epigenetic modifiers [5-azacytidine, nicotinamide, and suberoylanilide hydroxamic acid (SAHA)] were applied to induce the metabolites of <italic>Penicillium mallochii</italic> CCH01, a fungus isolated from the gut of <italic>Ectropis oblique</italic>. Metabolite profiles of <italic>P. mallochii</italic> CCH01 were obviously changed by SAHA treatment. Four metabolites (<bold>1</bold>–<bold>4</bold>), including two new natural sclerotioramine derivatives, isochromophilone XIV (<bold>1</bold>) and isochromophilone XV (<bold>2</bold>), and two known compounds, sclerotioramine (<bold>3</bold>) and (+)-sclerotiorin (<bold>4</bold>), were isolated and purified from <italic>P. mallochii</italic> CCH01 treated with SAHA. Their structures were determined by spectroscopic analyzes. Anti-phytopathogenic activities of the isolated compounds <bold>1</bold>–<bold>4</bold> were investigated under laboratory conditions, and compound <bold>4</bold> showed broad and important inhibition activities against <italic>Curvularia lunata</italic> (IC<sub>50</sub> = 2.1 μg/mL), <italic>Curvularia clavata</italic> (IC<sub>50</sub> = 21.0 μg/mL), <italic>Fusarium oxysporum</italic> f. sp. <italic>Mornordica</italic> (IC<sub>50</sub> = 40.4 μg/mL), and <italic>Botryosphaeria dothidea</italic> (IC<sub>50</sub> = 27.8 μg/mL), which were comparable to those of referenced cycloheximide, with IC<sub>50</sub> values of 0.3, 5.0, 12.4, and 15.3 μg/mL, respectively. Ingredients <bold>2</bold> and <bold>3</bold> showed selective and potent activities against <italic>Colletotrichum graminicola</italic> with IC<sub>50</sub> values of 29.9 and 9.7 μg/mL, respectively. Furthermore, the antibacterial bioassays showed that compounds <bold>3</bold> and <bold>4</bold> exhibited strong inhibition activities against <italic>Bacillus subtilis</italic>, 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 <bold>1</bold> showed a promising activity against <italic>Candida albicans</italic> (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 <italic>P. mallochii</italic>.</p>