title: Creation of an HDAC-based yeast screening method for evaluation of marine-derived actinomycetes: discovery of streptosetin A.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, California 94132, USA. amagata@sfsu.edu
authors.forename: Taro
authors.initials: T
authors.lastname: Amagata
authors.forename: Jing
authors.initials: J
authors.lastname: Xiao
authors.forename: Yi-Pei
authors.initials: YP
authors.lastname: Chen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Holsopple
authors.forename: Allen G
authors.initials: AG
authors.lastname: Oliver
authors.forename: Trevor
authors.initials: T
authors.lastname: Gokey
authors.forename: Anton B
authors.initials: AB
authors.lastname: Guliaev
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Minoura
mesh_terms: D039903:Actinobacteria / Q000737:chemistry*; D018360:Crystallography, X-Ray; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D008386:Marine Biology; D008968:Molecular Conformation; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D056572:Histone Deacetylase Inhibitors; D011760:Pyrrolidinones; D013764:Tetrahydronaphthalenes; C578444:streptosetin A