表观遗传试剂诱导滇重楼内生真菌Hypomyces sp.CLG4次生代谢产物的研究

采用高效液相色谱(HPLC)分析添加HDACI,500μM恩提诺特的H.sp.CLG4.培养萃取物与对照的差异,硅胶柱层析、反相柱层析、半制备高效液相等色谱方法对添加表观遗传试剂的Hypomyces sp.CLG4.次级代谢产物进行分离纯化,并利用现代波谱分析方法对化合物进行结构鉴定.研究组蛋白去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACI)表观遗传调控对分离自滇重楼菌寄生属菌株(Hypomyces sp.CLG4)产生次生代谢产物的影响.HPLC分析表明,恩替诺特可以诱导该菌株产生更为丰富的次生代谢产物,分离得到6个化合物,分别鉴定为:R-6-hydroxymellein(1),6-demethylkigelin(2),(3R)-6-methoxymellein(3),(3R)-6,7-dimethoxymellein(4),pyrolin(5),terrein(6).可见,组蛋白去乙酰化酶抑制剂的表观遗传调控可以显著提高菌株Hypomyces sp.CLG4.产生次生代谢的能力,化合物1～3、5和6为首次从该菌株中分离得到.

Epigenetic-induced secondary metabolites from the endophytic fungi Hypomyces sp.CLG4 isolated from Paris polyphylla var. yunnanensis

This research aimed to study the effects of the histone deacetylase inhibitor(HDACI) epigenetic reagent on the production of secondary metabolites by an entophytic strain Hypomyces sp.CLG4 isolated from Paris polyphylla var. yunnanensis. HPLC was used to analyze the secondary metabolites produced by the strain cultivated in the presence of 500 μM entinostat or free. The induced products were separated and purified by silica gel column chromatography, reversed-phase column chromatography, and semi-preparative HPLC. All the structures of the isolates were elucidated by analyses of the ~1H-and ~(13)C NMR data together with optical rotation value. The HPLC analysis showed that entinostat could significantly induce the production of secondary metabolites of H. sp. CLG4 strain. Six compounds were isolated and identified: R-6-hydroxymellein(1), terrain(2),(3R)-6-methoxymellein(3),(3R)-6,7-dimethoxymellein(4), pyrolin(5), and 6-demethylkigelin(6). The research concludes that the HDACI has a significant effect on the production of secondary metabolism of the entophytic fungus H. sp.CLG4. Compounds 1—3、 5 and 6 are isolated from the strain for the first time.