Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporiu...Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula Δhda A strain resulted in the isolation of twelve new diterpenoids including three cassanes(1-3), one cleistanthane(4), six pimaranes(5-10), and two isopimaranes(11 and 12) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2(matrix metalloproteinases family) in human breast cancer(MCF-7) cells.展开更多
基金supported financially by National Natural Science Foundation of China (Nos. 21502233 and 81522043)CAMS Initiative for Innovative Medicine (CAMS-I2M-1-010)+1 种基金the PUMC Youth Fund (33320140175)the State Key Laboratory Fund for Excellent Young Scientists to Youcai Hu (GTZB201401)
文摘Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula Δhda A strain resulted in the isolation of twelve new diterpenoids including three cassanes(1-3), one cleistanthane(4), six pimaranes(5-10), and two isopimaranes(11 and 12) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2(matrix metalloproteinases family) in human breast cancer(MCF-7) cells.
