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

Author: Jian BAI ¹ ; Rong MU ¹ ; Man DOU ¹ ; Daojiang YAN ¹ ; Bingyu LIU ¹ ; Qian WEI ¹ ; Jun WAN ¹ ; Yi TANG ¹ ; Youcai HU ¹
Author Information

1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Publication Type:Journal Article
Keywords: Calcarisporic acids; Calcarisporium arbuscula; Diterpenoid; Epigenetic genome mining; Matrix metalloproteinases inhibitor; Pimarane
From: Acta Pharmaceutica Sinica B 2018;8(4):687-697
CountryChina
Language:English
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 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 strain resulted in the isolation of twelve new diterpenoids including three cassanes (-), one cleistanthane (), six pimaranes (-), and two isopimaranes ( and ) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds and showed potent inhibitory effects on the expression of MMP1 and MMP2 (matrix metalloproteinases family) in human breast cancer (MCF-7) cells.