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Title: Forazoline A: Marine-derived polyketide with antifungal in vivo efficacy

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. In this paper, using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.

Authors:
 [1];  [1];  [1];  [1];  [2];  [1];  [1];  [2];  [1];  [1];  [1];  [1]
+ Show Author Affiliations
  1. Univ. of Wisconsin, Madison, WI (United States)
  2. Univ. of Minnesota-Twin Cities, Minneapolis, MN (United States)
Publication Date:
Research Org.:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1342730
Grant/Contract Number:  
FC02-07ER64494
Resource Type:
Accepted Manuscript
Journal Name:
Angewandte Chemie (International Edition)
Additional Journal Information:
Journal Name: Angewandte Chemie (International Edition); Journal Volume: 53; Journal Issue: 43; Journal ID: ISSN 1433-7851
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; antifungal agents; genomics; natural products; NMR spectroscopy; structure elucidation

Citation Formats

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., and Bugni, Tim S. Forazoline A: Marine-derived polyketide with antifungal in vivo efficacy. United States: N. p., 2014. Web. doi:10.1002/anie.201405990.
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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. Forazoline A: Marine-derived polyketide with antifungal in vivo efficacy. United States. https://doi.org/10.1002/anie.201405990
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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., and Bugni, Tim S. Thu . "Forazoline A: Marine-derived polyketide with antifungal in vivo efficacy". United States. https://doi.org/10.1002/anie.201405990. https://www.osti.gov/servlets/purl/1342730.
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@article{osti_1342730,
title = {Forazoline A: Marine-derived polyketide with antifungal in vivo efficacy},
author = {Wyche, Thomas P. and Piotrowski, Jeff S. and Hou, Yanpeng and Braun, Doug and Deshpande, Raamesh and McIlwain, Sean and Ong, Irene M. and Myers, Chad L. and Guzei, Ilia A. and Westler, William M. and Andes, David R. and Bugni, Tim S.},
abstractNote = {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. In this paper, using yeast chemical genomics, we propose that forazoline A operated through a new mechanism of action with a phenotypic outcome of disrupting membrane integrity.},
doi = {10.1002/anie.201405990},
journal = {Angewandte Chemie (International Edition)},
number = 43,
volume = 53,
place = {United States},
year = {Thu Sep 04 00:00:00 EDT 2014},
month = {Thu Sep 04 00:00:00 EDT 2014}
}
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https://doi.org/10.1002/anie.201405990
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