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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 Hsp90? binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90? modulators in a new axolotl embryo tail regeneration (ETR) assay as a potential new whole animal assay for Hsp90 modulator discovery.

SUBMITTER: Wang X 

PROVIDER: S-EPMC5339036 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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

Wang Xiachang X   Zhang Yinan Y   Ponomareva Larissa V LV   Qiu Qingchao Q   Woodcock Ryan R   Elshahawi Sherif I SI   Chen Xiabin X   Zhou Ziyuan Z   Hatcher Bruce E BE   Hower James C JC   Zhan Chang-Guo CG   Parkin Sean S   Kharel Madan K MK   Voss S Randal SR   Shaaban Khaled A KA   Thorson Jon S JS  

Angewandte Chemie (International ed. in English) 20170131 11


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 pr  ...[more]

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