Journal of Natural Products, volume 82, issue 12, pages 3469-3476

Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces

Wang Xiachang 1
Elshahawi Sherif I. 2
Ponomareva Larissa
Ye Qing 3
Liu Yang
Copley Gregory C 4
Hower James C. 4
Hatcher Bruce E 5
Kharel M. K. 6
Van Lanen Steven G.
SHE Qing-Bai 3
Voss S.
Thorson Jon S.
Shaaban Khaled A
2
 
Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Irvine, California 92618, United States
3
 
Markey Cancer Center, Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, United States
4
 
Center for Applied Energy Research, University of Kentucky, Lexington, Kentucky 40511, United States
5
 
Division of Water, Kentucky Energy and Environment Cabinet, 2642 Russellville Road, Bowling Green, Kentucky 42101, United States
6
 
School of Pharmacy, University of Maryland Eastern Shore, Princess Anne, Maryland 21853, United States
Publication typeJournal Article
Publication date2019-12-13
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor5.1
ISSN01633864, 15206025
Organic Chemistry
Drug Discovery
Pharmacology
Pharmaceutical Science
Molecular Medicine
Complementary and alternative medicine
Analytical Chemistry
Abstract
We report the isolation and characterization of three new nybomycins (nybomycins B-D, 1-3) and six known compounds (nybomycin, 4; deoxynyboquinone, 5; α-rubromycin, 6; β-rubromycin, 7; γ-rubromycin, 8; and [2α(1E,3E),4β]-2-(1,3-pentadienyl)-4-piperidinol, 9) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate Streptomyces sp. AD-3-6. Nybomycin D (3) and deoxynyboquinone (5) displayed moderate (3) to potent (5) cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins 6-8 displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity. Assessment of the impact of 3 or 5 cancer cell line treatment on 4E-BP1 phosphorylation, a predictive marker of ROS-mediated control of cap-dependent translation, also revealed deoxynyboquinone (5)-mediated downstream inhibition of 4E-BP1p. Evaluation of 1-9 in a recently established axolotl embryo tail regeneration assay also highlighted the prototypical telomerase inhibitor γ-rubromycin (8) as a new inhibitor of tail regeneration. Cumulatively, this work highlights an alternative nybomycin production strain, a small set of new nybomycin metabolites, and previously unknown functions of rubromycins (antifungal activity and inhibition of tail regeneration) and also provides a basis for revision of the previously proposed nybomycin biosynthetic pathway.

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GOST Copy
Wang X. et al. Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces // Journal of Natural Products. 2019. Vol. 82. No. 12. pp. 3469-3476.
GOST all authors (up to 50) Copy
Wang X., Elshahawi S. I., Ponomareva L., Ye Q., Liu Y., Copley G. C., Hower J. C., Hatcher B. E., Kharel M. K., Van Lanen S. G., SHE Q., Voss S., Thorson J. S., Shaaban K. A. Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces // Journal of Natural Products. 2019. Vol. 82. No. 12. pp. 3469-3476.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1021/acs.jnatprod.9b01015
UR - https://doi.org/10.1021%2Facs.jnatprod.9b01015
TI - Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces
T2 - Journal of Natural Products
AU - Copley, Gregory C
AU - Hatcher, Bruce E
AU - Wang, Xiachang
AU - Elshahawi, Sherif I.
AU - Hower, James C.
AU - Van Lanen, Steven G.
AU - Thorson, Jon S.
AU - Shaaban, Khaled A
AU - Ponomareva, Larissa
AU - Ye, Qing
AU - Liu, Yang
AU - Kharel, M. K.
AU - SHE, Qing-Bai
AU - Voss, S.
PY - 2019
DA - 2019/12/13 00:00:00
PB - American Chemical Society (ACS)
SP - 3469-3476
IS - 12
VL - 82
PMID - 31833370
SN - 0163-3864
SN - 1520-6025
ER -
BibTex |
Cite this
BibTex Copy
@article{2019_Wang
author = {Gregory C Copley and Bruce E Hatcher and Xiachang Wang and Sherif I. Elshahawi and James C. Hower and Steven G. Van Lanen and Jon S. Thorson and Khaled A Shaaban and Larissa Ponomareva and Qing Ye and Yang Liu and M. K. Kharel and Qing-Bai SHE and S. Voss},
title = {Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces},
journal = {Journal of Natural Products},
year = {2019},
volume = {82},
publisher = {American Chemical Society (ACS)},
month = {dec},
url = {https://doi.org/10.1021%2Facs.jnatprod.9b01015},
number = {12},
pages = {3469--3476},
doi = {10.1021/acs.jnatprod.9b01015}
}
MLA
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MLA Copy
Wang, Xiachang, et al. “Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated Streptomyces.” Journal of Natural Products, vol. 82, no. 12, Dec. 2019, pp. 3469-3476. https://doi.org/10.1021%2Facs.jnatprod.9b01015.
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