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

Epigenetic modifications have been proved to be a powerful technique to activate silent gene clusters and had led to diverse secondary metabolites in fungi. Investigation of the crude extract of Calcarisporium arbuscula ΔhdaA strain, in which a histone H3 deacetylase was deleted, resulted in the isolation of twelve new diterpenoids including three cassanes (1−3), one cleistanthane (4), six pimaranes (5−10), and two isopimaranes (11−12). Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2 (matrix metalloproteinases family) in human breast cancer cells.185