Isolation, Structure Elucidation, and Biological Activity of Altersolanol P Using Staphylococcus aureus Fitness Test Based Genome-Wide Screening

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• 作者：John Ondeyka ; Alexei V. Buevich ; R. Thomas Williamson ; Deborah L. Zink ; Jon D. Polishook ; James Occi ; Francisca Vicente ; Angela Basilio ; Gerald F. Bills ; Robert G. K. Donald ; John W. Phillips ; Michael A. Goetz ; Sheo B. Singh
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：March 28, 2014
• 年：2014
• 卷：77
• 期：3
• 页码：497-502
• 全文大小：311K
• 年卷期：v.77,no.3(March 28, 2014)
• ISSN：1520-6025

文摘

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 ¹H and ¹³C NMR shifts were well aligned with the corresponding chemical shifts predicted by DFT calculations. Altersolanol P exhibited Gram-positive antibacterial activity (MIC range 1鈥? 渭g/mL) and inhibited the growth of Gram-negative Haemophilus influenzae (MIC 2 渭g/mL). The isolation, structure elucidation, and antibacterial activity of altersolanol P are described.