Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe

Xiachang Wang; Yinan Zhang; Larissa V. Ponomareva; Qingchao Qiu; Ryan Woodcock; Sherif I. Elshahawi; Xiabin Chen; Ziyuan Zhou; Bruce E. Hatcher; James C. Hower; Chang Guo Zhan; Sean Parkin; Madan K. Kharel; S. Randal Voss; Khaled A. Shaaban; Jon S. Thorson

doi:10.1002/anie.201612447

Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe

Xiachang Wang, Yinan Zhang, Larissa V. Ponomareva, Qingchao Qiu, Ryan Woodcock, Sherif I. Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E. Hatcher, James C. Hower, Chang Guo Zhan, Sean Parkin, Madan K. Kharel, S. Randal Voss, Khaled A. Shaaban, Jon S. Thorson

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

32 Scopus citations

Abstract

Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.

Original language	English
Pages (from-to)	2994-2998
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	56
Issue number	11
DOIs	https://doi.org/10.1002/anie.201612447
State	Published - Mar 6 2017

Bibliographical note

Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Funding

This work was supported by National Institutes of Health grants R24 OD21479 (SRV, JST), T32 DA016176 (YZ), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center, and the National Center for Advancing Translational Sciences (UL1TR001998).

Funders	Funder number
University of Kentucky
National Institutes of Health (NIH)	R24 OD21479
National Center for Advancing Translational Sciences (NCATS)	UL1TR001998
University of Kentucky Markey Cancer Center
Japan Science and Technology Agency	T32 DA016176

Keywords

Hsp90
ansamycin
axolotl
biomimetic synthesis
regeneration

ASJC Scopus subject areas

Catalysis
General Chemistry

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10.1002/anie.201612447

Cite this

Wang, X., Zhang, Y., Ponomareva, L. V., Qiu, Q., Woodcock, R., Elshahawi, S. I., Chen, X., Zhou, Z., Hatcher, B. E., Hower, J. C., Zhan, C. G., Parkin, S., Kharel, M. K., Voss, S. R., Shaaban, K. A., & Thorson, J. S. (2017). Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe. Angewandte Chemie - International Edition, 56(11), 2994-2998. https://doi.org/10.1002/anie.201612447

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title = "Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe",

abstract = "Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.",

keywords = "Hsp90, ansamycin, axolotl, biomimetic synthesis, regeneration",

author = "Xiachang Wang and Yinan Zhang and Ponomareva, {Larissa V.} and Qingchao Qiu and Ryan Woodcock and Elshahawi, {Sherif I.} and Xiabin Chen and Ziyuan Zhou and Hatcher, {Bruce E.} and Hower, {James C.} and Zhan, {Chang Guo} and Sean Parkin and Kharel, {Madan K.} and Voss, {S. Randal} and Shaaban, {Khaled A.} and Thorson, {Jon S.}",

note = "Publisher Copyright: {\textcopyright} 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2017",

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doi = "10.1002/anie.201612447",

language = "English",

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Wang, X, Zhang, Y, Ponomareva, LV, Qiu, Q, Woodcock, R, Elshahawi, SI, Chen, X, Zhou, Z, Hatcher, BE, Hower, JC, Zhan, CG , Parkin, S, Kharel, MK, Voss, SR , Shaaban, KA & Thorson, JS 2017, 'Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe', Angewandte Chemie - International Edition, vol. 56, no. 11, pp. 2994-2998. https://doi.org/10.1002/anie.201612447

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AU - Wang, Xiachang

AU - Zhang, Yinan

AU - Ponomareva, Larissa V.

AU - Qiu, Qingchao

AU - Woodcock, Ryan

AU - Elshahawi, Sherif I.

AU - Chen, Xiabin

AU - Zhou, Ziyuan

AU - Hatcher, Bruce E.

AU - Hower, James C.

AU - Zhan, Chang Guo

AU - Parkin, Sean

AU - Kharel, Madan K.

AU - Voss, S. Randal

AU - Shaaban, Khaled A.

AU - Thorson, Jon S.

PY - 2017/3/6

Y1 - 2017/3/6

N2 - Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.

AB - Four cyclopentenone-containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD-23-14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19-hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.

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KW - axolotl

KW - biomimetic synthesis

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Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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