Pinpointing Pseurotins from a Marine-Derived Aspergillus as Tools for Chemical Genetics Using a Synthetic Lethality Yeast Screen

Claudia M. Boot†, Nadine C. Gassner‡, Jennifer E. Compton‡, Karen Tenney‡, Craig M. Tamble‡, R. Scott Lokey‡, Theodore R. Holman‡ and Phillip Crews*†‡
Department of Ocean Sciences and Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064
J. Nat. Prod., 2007, 70 (10), pp 1672–1675
DOI: 10.1021/np070307c
Publication Date (Web): October 12, 2007
Copyright © 2007 The American Chemical Society and std np
†

Dept. of Ocean Sciences.

,
‡

Dept. of Chemistry and Biochemistry.

,
* To whom correspondence should be addressed. Tel: 831-459-2603 . Fax: 831-459-2935. E-mail: phil@chemistry.ucsc.edu.

Abstract

Abstract Image

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.

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue October 26, 2007
  • Article ASAPOctober 12, 2007
  • Received: June 26, 2007

Recommend & Share

Related Content

Other ACS content by these authors: