Epigenetic modification in histone deacetylase deletion strain of Calcarisporium arbuscula leads to diverse diterpenoids

Abstract 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 ΔhdaA 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.