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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Published in Angewandte Chemie, v. 56, issue 11, p. 2994-2998.

© 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim

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This is the peer reviewed version of the following article: Wang, X., Zhang, Y., Ponomareva, L. V., Qiu, Q., Woodcock, R., Elshahawi, S. I., ... Thorson, J. S. (2017). Mccrearamycins A–D, geldanamycin‐derived cyclopentenone macrolactams from an Eastern Kentucky abandoned coal Mine microbe. Angewandte Chemie, 56(11), 2994-2998, which has been published in final form at https://doi.org/10.1002/anie.201612447. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

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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).

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Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201612447.

anie201612447-sup-0001-misc_information.pdf (8375 kB)
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