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Isolation, structure elucidation, and biological activity of altersolanol P using Staphylococcus aureus fitness test based genome-wide screening.

Authors
  • Ondeyka, John
  • Buevich, Alexei V
  • Williamson, R Thomas
  • Zink, Deborah L
  • Polishook, Jon D
  • Occi, James
  • Vicente, Francisca
  • Basilio, Angela
  • Bills, Gerald F
  • Donald, Robert G K
  • Phillips, John W
  • Goetz, Michael A
  • Singh, Sheo B
Type
Published Article
Journal
Journal of Natural Products
Publisher
American Chemical Society
Publication Date
Mar 28, 2014
Volume
77
Issue
3
Pages
497–502
Identifiers
DOI: 10.1021/np400759f
PMID: 24428261
Source
Medline
License
Unknown

Abstract

Bacteria continue to evade existing antibiotics by acquiring resistance by various mechanisms, leading to loss of antibiotic effectiveness. To avoid an epidemic from infections of incurable drug-resistant bacteria, new antibiotics with new modes of action are desperately needed. Using a genome-wide mechanism of action-guided whole cell screening approach based on antisense Staphylococcus aureus fitness test technology, we report herein the discovery of altersolanol P (1), a new tetrahydroanthraquinone from an unknown fungus from the Hypocreales isolated from forest litter collected in Puerto Rico. The structure was elucidated by high-resolution mass spectrometry and 2D NMR spectroscopy. Relative stereochemistry was established by NOESY correlations, and absolute configuration was deduced by the application of MPA ester-based methodology. Observed (1)H and (13)C NMR shifts were well aligned with the corresponding chemical shifts predicted by DFT calculations. Altersolanol P exhibited Gram-positive antibacterial activity (MIC range 1-8 μg/mL) and inhibited the growth of Gram-negative Haemophilus influenzae (MIC 2 μg/mL). The isolation, structure elucidation, and antibacterial activity of altersolanol P are described.

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