Regulation of secondary metabolites in the endophytic fungus Penicillium sp. KMU18029 by the chemical epigenetic modifier 5-azacitidine

Abstract

The chemical epigenetic modifier 5-azacitidine (5-Aza C), a DNA methyltransferase inhibitor, was used to manipulate the endophytic fungus Penicillium sp. KMU18029. From its rice fermentation extract, a new polyketone compound (3S,4R)-3,4,8-trihydroxy-6-methyl-3,4-dihydronaphthalen-1(2H)-one (1), along with 13 known compounds, 3,4,8-trihydroxy-6-(hydroxymethyl)-3,4-dihydronaphthalen-1(2H)-one (2), decaturin B (3), 15-hydroxydecaturin A (4), oxalicine A (5), pileotin A (6), pyrandecarurin A (7), decaturenol A (8), decaturenoid (9), penisarins A (10), oxaline (11), (4E,8E)-N-D-2'-hydroxyocta-decanoyl-1-O-β-D-glycopy-ranosyl-9-methyl-4,8-sphingadienine (12), ergosterol (13) and stigma-5-en-3-O-β-glucoside (14), were separated. Among the known compounds, 2, 7, 12 and 14 were not found in our previous research on this strain. The structure of the new compound was identified by spectroscopic techniques such as HR-ESIMS, 1D NMR, 2D NMR and CD. Furthermore, all the isolated compounds were tested for their antimicrobial activities, and only compounds 1, 2 and 11 showed weak activities against S. aureus, with MICs of 128 μg/mL.

Graphical Abstract

Keywords:

• Chemical epigenetic modification
• 5-azacitidine
• Penicillium
• Antibacterial activity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Scientific Research Foundation of Yunnan Province Science and Technology Department (Grant Nos. 202201AY070001-009 and 202201AY070001-010) and the Scientific Research Foundation of Yunnan Provincial Department of Education (Grant No. 2022J0222).