Creation of an HDAC-Based Yeast Screening Method for Evaluation of Marine-Derived Actinomycetes: Discovery of Streptosetin A

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 1D
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.