Li Gang, Kusari Souvik, Golz Christopher, Laatsch Hartmut, Strohmann Carsten, Spiteller Michael
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.
Inorganic Chemistry, Department of Chemistry and Chemical Biology, TU Dortmund , Otto-Hahn-Straße 6, 44221 Dortmund, Germany.
J Nat Prod. 2017 Apr 28;80(4):983-988. doi: 10.1021/acs.jnatprod.6b00997. Epub 2017 Mar 23.
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.
从中药苍耳中分离出的一种内生真菌，青霉属LG41菌株，使用烟酰胺（一种NAD依赖性组蛋白脱乙酰酶（HDAC）抑制剂）进行表观遗传调控。对该内生菌的表观遗传刺激导致两种含十氢化萘的新化合物——青霉菌素C和D（3和4）产量增加，同时还产生了两种生物合成相关的已知化合物——优贾瓦尼醇A（1）和青霉菌素醇A（2）。通过使用LC-HRMS、NMR、旋光和ECD计算以及单晶X射线衍射进行广泛的光谱分析，阐明了新化合物的结构和立体化学。LC-MS分析表明，化合物3和4分别与两种和三种顺式/反式异构体处于化学平衡状态。化合物4对金黄色葡萄球菌具有活性，MIC为0.1μg/mL，并对人急性单核细胞白血病细胞系（THP-1）表现出显著的细胞毒性。我们已经证明，HDAC抑制剂烟酰胺可提高内生青霉属LG41菌株产生化合物3和4的产量，有助于它们的分离、结构解析以及生物活性评估。
