title: Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen.
abstract: A new compound of mixed polyketide synthase-nonribosomal peptide synthetase (PKS/NRPS) origin, 11- O-methylpseurotin A ( 1), was identified from a marine-derived Aspergillus fumigatus. Bioassay-guided fractionation using a yeast halo assay with wild-type and cell cycle-related mutant strains of Saccharomyces cerevisiae resulted in the isolation of 1, which selectively inhibited a Hof1 deletion strain. Techniques including 1D and 2D NMR, HRESIMS, optical rotation, J-based analysis, and biosynthetic parallels were used in the elucidation of the planar structure and absolute configuration of 1. A related known compound, pseurotin A ( 2), was also isolated and found to be inactive in the yeast screen.
authors.affiliation: Department of Ocean Sciences and Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Boot
authors.forename: Nadine C
authors.initials: NC
authors.lastname: Gassner
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Compton
authors.forename: Karen
authors.initials: K
authors.lastname: Tenney
authors.forename: Craig M
authors.initials: CM
authors.lastname: Tamble
authors.forename: R Scott
authors.initials: RS
authors.lastname: Lokey
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holman
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
mesh_terms: D001230:Aspergillus / Q000737:chemistry*; D002176:Candida albicans / Q000378:metabolism; D008386:Marine Biology; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D015394:Molecular Structure; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017385:Sequence Homology
chemical_list: C524991:11-O-methylpseurotin A; C116847:HOF1 protein, S cerevisiae; D008869:Microtubule-Associated Proteins; D009097:Multienzyme Complexes; D011760:Pyrrolidinones; D029701:Saccharomyces cerevisiae Proteins; C012013:pseurotin; D048630:Polyketide Synthases; D010453:Peptide Synthases