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Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen.

Authors
  • Cm, Boot
  • Nc, Gassner
  • Je, Compton
  • K, Tenney
  • Cm, Tamble
  • Rs, Lokey
  • Tr, Holman
  • P, Crews
Type
Published Article
Journal
Journal of Natural Products
Publisher
American Chemical Society
Volume
70
Issue
10
Pages
1672–1675
Source
UCSC Cancer biomedical-ucsc
License
Unknown

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.

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