TY - JOUR
T1 - Mccrearamycins A–D, Geldanamycin-Derived Cyclopentenone Macrolactams from an Eastern Kentucky Abandoned Coal Mine Microbe
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.
N1 - Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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.
KW - Hsp90
KW - ansamycin
KW - axolotl
KW - biomimetic synthesis
KW - regeneration
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U2 - 10.1002/anie.201612447
DO - 10.1002/anie.201612447
M3 - Article
C2 - 28140487
AN - SCOPUS:85011295961
SN - 1433-7851
VL - 56
SP - 2994
EP - 2998
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 11
ER -