Epigenetic modification in histone deacetylase deletion strain of Calcarisporium arbuscula leads to diverse diterpenoids
Epigenetic modification in histone deacetylase deletion strain of Calcarisporium arbuscula leads to diverse diterpenoids
复制标题
丛枝状孢菌组蛋白脱乙酰酶缺失菌株的表观遗传修饰产生多种二萜类化合物
DOI：
10.1016/j.apsb.2017.12.012
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发表时间：
2018-07-01
影响因子：
14.5
通讯作者：
Hu, Youcai
中科院分区：
文献类型：
--
作者：
Bai, Jian;Mu, Rong;Hu, Youcai
表观遗传修饰已被证明是激活真菌沉默基因簇并产生多种次生代谢产物的有效途径。在此之前，组蛋白H3脱乙酰酶在Calcarisporium arbuscula的失活导致多效性激活和超过75%的生物合成基因的过度表达和10种化合物的分离。进一步研究了C. arbuscula Delta hdaA菌株导致分离了12种新的二萜类化合物，包括三种卡散烷（1-3）、一种噻烷（4）、六种海松烷（5-10）和两种异海松烷（11和12）沿着两种已知的噻烷类似物。通过大量的NMR光谱数据分析确定了它们的结构。化合物2和4对人乳腺癌（MCF-7）细胞中MMP 1和MMP 2（基质金属蛋白酶家族）的表达显示出有效的抑制作用。(C)2018年中国药学会、中国医学科学院药物研究所。制作和主办：Elsevier B. V.
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 Delta hdaA 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. (C) 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.