Creation of an HDAC-Based Yeast Screening Method for Evaluation of Marine-Derived Actinomycetes: Discovery of Streptosetin A
Creation of an HDAC-Based Yeast Screening Method for Evaluation of Marine-Derived Actinomycetes: Discovery of Streptosetin A
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DOI：
10.1021/np300640g
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发表时间：
2012-12-01
影响因子：
5.1
通讯作者：
Minoura, Katsuhiko
中科院分区：
文献类型：
--
作者：
Amagata, Taro;Xiao, Jing;Minoura, Katsuhiko
A histone deacetylase (HDAC)-based yeast assay employing a URA3 reporter gene was applied as a primary screen to evaluate a marine-derived actinomycete extract library and identify human class III HDAC (SIRT) inhibitors. On the basis of the bioassay-guided purification, a new compound designated as streptosetin A (1) was obtained from one of the active strains identified through the yeast assay. The gross structure of the new compound was elucidated from the ID and 2D NMR data. The absolute stereostructure of 1 was determined based on X-ray crystal structure analysis and simulation of ECD spectra using time-dependent density functional theory calculations. This compound showed weak inhibitory activity against yeast Sir2p and human SIRT1 and SIRT2.
