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

  • J Nat Prod. 2007 Oct;70(10):1672-5. doi: 10.1021/np070307c.
Claudia M Boot  1 ,  Nadine C Gassner ,  Jennifer E Compton ,  Karen Tenney ,  Craig M Tamble ,  R Scott Lokey ,  Theodore R Holman ,  Phillip Crews
Affiliations
  • 1. Department of Ocean Sciences and Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, USA.
PMID: 17929896 DOI: 10.1021/np070307c
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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