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- Title
Forazoline A: Marine-Derived Polyketide with Antifungal In Vivo Efficacy.
- Authors
Wyche, Thomas P.; Piotrowski, Jeff S.; Hou, Yanpeng; Braun, Doug; Deshpande, Raamesh; McIlwain, Sean; Ong, Irene M.; Myers, Chad L.; Guzei, Ilia A.; Westler, William M.; Andes, David R.; Bugni, Tim S.
- Abstract
Forazoline A, a novel antifungal polyketide with in vivo efficacy against Candida albicans, was discovered using LCMS-based metabolomics to investigate marine-invertebrateassociated bacteria. Forazoline A had a highly unusual and unprecedented skeleton. Acquisition of 13C-³C gCOSY and 13C-5N 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.
- Subjects
POLYKETIDES; ANTIFUNGAL agents; CANDIDA albicans; CHEMOGENOMICS; LIQUID chromatography-mass spectrometry
- Publication
Angewandte Chemie International Edition, 2014, Vol 53, Issue 43, p11583
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201405990