Forazoline A: Marine-Derived Polyketide with Antifungal in Vivo Efficacy

Thomas P. Wyche, Jeff S. Piotrowski, Yanpeng Hou, Doug Braun, Raamesh Deshpande, Sean McIlwain, Irene M. Ong, Chad L. Myers, Ilia A. Guzei, William M. Westler, David R. Andes, Tim S. Bugni

Research output: Contribution to journalArticlepeer-review

76 Scopus citations


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 languageEnglish (US)
Pages (from-to)11583-11586
Number of pages4
JournalAngewandte Chemie - International Edition
Issue number43
StatePublished - 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.


  • NMR spectroscopy
  • antifungal agents
  • genomics
  • natural products
  • structure elucidation


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