Abstract
Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS-based metabolomics to investigate marine-invertebrate-associated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of 13C-13C gCOSY and 13C-15N HMQC NMR data provided the direct carbon-carbon and carbon-nitrogen connectivity, respectively. This approach represents the first example of determining direct 13C-15N connectivity for a natural product. Using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.
Original language | English (US) |
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Pages (from-to) | 11583-11586 |
Number of pages | 4 |
Journal | Angewandte Chemie - International Edition |
Volume | 53 |
Issue number | 43 |
DOIs | |
State | Published - Oct 20 2014 |
Bibliographical note
Funding Information:We acknowledge financial support from the University of Wisconsin-Madison School of Pharmacy. This work was also funded by the NIH, NIGMS Grant R01 GM092009, and in part by R01 GM104192.
Publisher Copyright:
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Keywords
- NMR spectroscopy
- antifungal agents
- genomics
- natural products
- structure elucidation