Epigenetic Modulation of Endophytic Eupenicillium sp. LG41 by a Histone Deacetylase Inhibitor for Production of Decalin-Containing Compounds.
An endophytic fungus, Eupenicillium sp. LG41, isolated from the Chinese medicinal plant Xanthium sibiricum, was subjected to epigenetic modulation using an NAD+-dependent histone deacetylase (HDAC) inhibitor, nicotinamide. Epigenetic stimulation of the endophyte led to enhanced production of two new decalin-containing compounds, eupenicinicols C and D (3 and 4), along with two biosynthetically related known compounds, eujavanicol A (1) and eupenicinicol A (2). The structures and stereochemistry of the new compounds were elucidated by extensive spectroscopic analysis using LC-HRMS, NMR, optical rotation, and ECD calculations, as well as single-crystal X-ray diffraction. Compounds 3 and 4 exist in chemical equilibrium with two and three cis/trans isomers, respectively, as revealed by LC-MS analysis. Compound 4 was active against Staphylococcus aureus with an MIC of 0.1 μg/mL and demonstrated marked cytotoxicity against the human acute monocytic leukemia cell line (THP-1). We have shown that the HDAC inhibitor, nicotinamide, enhanced the production of compounds 3 and 4 by endophytic Eupenicillium sp. LG41, facilitating their isolation, structure elucidation, and evaluation of their biological activities.
Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund , Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
Gang
G
Li
Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund , Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
Souvik
0000-0002-4685-0794
S
Kusari
Inorganic Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund , Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
Christopher
C
Golz
Institute for Organic and Biomolecular Chemistry, University of Göttingen , Tammannstrasse 2, D-37077 Göttingen, Germany.
Hartmut
H
Laatsch
Inorganic Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund , Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
Carsten
0000-0002-4787-2135
C
Strohmann
Institute of Environmental Research (INFU), Department of Chemistry and Chemical Biology, Chair of Environmental Chemistry and Analytical Chemistry, TU Dortmund , Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
Michael
M
Spiteller
D000900:Anti-Bacterial Agents / Q000737:chemistry; D001412:Bacillus subtilis / Q000187:drug effects; D018360:Crystallography, X-Ray; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D060026:Endophytes / Q000737:chemistry; D055324:Eupenicillium / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D031210:Xanthium / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D004365:Drugs, Chinese Herbal; D056572:Histone Deacetylase Inhibitors; D009281:Naphthalenes; C524240:eujavanicol A; C000599080:eupenicinicol A; C007229:decalin