化学表观遗传学抑制剂诱导真菌Pleosporales sp.SSJ-1天然产物研究  

Study on the natural products induced by chemical epigenetic inhibitors from fungus Pleosporales sp.SSJ-1

作　　者：曾洁醇 杨润 李琪 汪伟光 ZENG Jie-chun;YANG Run;LI Qi;WANG Wei-guang(Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes,State Ethnic Affairs Commission,School of Ethnic Medicine,Yunnan Minzu University,Kunming 650500,China)

机构地区：[1]云南民族大学国家民委民族药内生菌天然产物合成生物学重点实验室民族医药学院,云南昆明650500

出　　处：《云南民族大学学报（自然科学版）》2023年第2期131-137,共7页Journal of Yunnan Minzu University:Natural Sciences Edition

基　　金：国家自然科学基金(31960095);云南省应用基础项目(202101AS070022);云南省万人计划-青年拔尖人才.

摘　　要：对云南油杉来源的内生真菌Pleosporales sp.SSJ-1进行化学表观遗传修饰并研究其次生代谢产物.利用组蛋白去乙酰化酶抑制剂恩替诺特(Entinostat)对菌株Pleosporales sp.SSJ-1进行诱导,采用正相硅胶柱色谱、ODS反相柱色谱和半制备型高效液相色谱等手段对粗提物进行分离纯化,通过NMR、质谱、旋光等进行结构解析.从菌株Pleosporales sp.SSJ-1的诱导发酵物中分离得到6个化合物,其中化合物1为新化合物.分别鉴定为(2 S,4R)-2,3-dihydro-2-methyl-benzopyran-4,5-diol(1)、(4 S)-4,8-dihydroxy-α-tetralone(2)、(R)-2,3-dihydro-5-hydroxy-2-methylchromen-4-one(3)、(2R,4R)-3,4-dihydro-4-methoxy-2-methyl-2H-chromen-5-ol(4)、(R)-2,3-dihydro-5-methoxy-2-methylchromen-4-one(5)、(2 R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol(6).所有化合物在40μmol/L浓度下均未表现出SARS-CoV-2 M pro抑制活性.研究表明所有化合物可以通过化学表观遗传学抑制剂诱导产生,皆为首次从格孢腔菌属中分离得到;组蛋白去乙酰化抑制剂是一个有效的激活真菌沉默基因簇表达新次生代谢产物的方法.In this paper,the endophytic fungus Pleosporales sp.SSJ-1 from Taxus yunnanensis was modified by chemical epigenetics and its secondary metabolites were studied.A histone deacetylase inhibitor,Entinostat,was used to induce the strain Pleosporales sp.SSJ-1,the crude extract was isolated and purified by normal phase silica gel column chromatography,ODS reverse phase column chromatography,and semi preparative high performance liquid chromatography,and the structure was analyzed by NMR,mass spectrometry,and optical rotation.Six compounds were isolated from the inducible fermentation of strain Pleosporales sp.SSJ-1,including one new compound 1.They were identified as(2S,4R)-2,3-dihydro-2-methyl-benzopyran-4,5-diol(1),(4S)-4,8-dihydroxy-α-tetralone(2),(R)-2,3-dihydro-5-hydroxy-2-methylchromen-4-one(3),(2 R,4R)-3,4-dihydro-4-methoxy-2-methyl-2H-chromen-5-ol(4),(R)-2,3-dihydro-5-methoxy-2-methylchromen-4-one(5),and(2 R,4S)-5-methoxy-2-methyl-3,4-dihydro-2H-1-benzopyran-4-ol(6).All the compounds showed no SARS-CoV-2 M pro inhibitory activity at the concentration of 40μmol/L.In conclusion,all the compounds can be induced by chemical epigenetic inhibitors,and all of them have been isolated from the genus Granulospora for the first time.This study demonstrated that histone deacetylation inhibitors are an effective method to activate the expression of new secondary metabolites by fungal silencing gene clusters.

关 键 词：表观遗传 内生真菌 恩替诺特 组蛋白修饰 苯并吡喃衍生物 

分 类 号：Q936[生物学—微生物学]