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

doi:10.1002/anie.201405990

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

Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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)
Pages (from-to)	11583-11586
Number of pages	4
Journal	Angewandte Chemie - International Edition
Volume	53
Issue number	43
DOIs	https://doi.org/10.1002/anie.201405990
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

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/anie.201405990

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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.",

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

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: {\textcopyright} 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

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month = oct,

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doi = "10.1002/anie.201405990",

language = "English (US)",

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AU - Wyche, Thomas P.

AU - Piotrowski, Jeff S.

AU - Hou, Yanpeng

AU - Braun, Doug

AU - Deshpande, Raamesh

AU - McIlwain, Sean

AU - Ong, Irene M.

AU - Myers, Chad L.

AU - Guzei, Ilia A.

AU - Westler, William M.

AU - Andes, David R.

AU - Bugni, Tim S.

N1 - 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.

PY - 2014/10/20

Y1 - 2014/10/20

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AB - 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.

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KW - genomics

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KW - structure elucidation

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

Abstract

Bibliographical note

Keywords

UN SDGs

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