Journal of the American Chemical Society, volume 141, issue 9, pages 3910-3919

Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria

Wu Changsheng 1
Shang Zhuo 1
Lemetre Christophe 1
Ternei Melinda A 1
Brady Sean F. 1
1
 
Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York 10065, United States
Publication typeJournal Article
Publication date2019-02-08
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor15
ISSN00027863, 15205126
PubMed ID:  30735616
General Chemistry
Catalysis
Biochemistry
Colloid and Surface Chemistry
Abstract
The growing threat of antibiotic resistance necessitates the discovery of antibiotics that are active against resistant pathogens. Calcium-dependent antibiotics are a small family of structurally diverse acidic lipopeptides assembled by nonribosomal peptide synthetases (NRPSs) that are known to display various modes of action against antibiotic-resistant pathogens. Here we use NRPS adenylation (AD) domain sequencing to guide the identification, recovery, and cloning of the cde biosynthetic gene cluster from a soil metagenome. Heterologous expression of the cde biosynthetic gene cluster led to the production of cadasides A (1) and B (2), a subfamily of acidic lipopeptides that is distinct from previously characterized calcium-dependent antibiotics in terms of both overall structure and acidic residue rich peptide core. The cadasides inhibit the growth of multidrug-resistant Gram-positive pathogens by disrupting cell wall biosynthesis in the presence of high concentrations of calcium. Interestingly, sequencing of AD domains from diverse soils revealed that sequences predicted to arise from cadaside-like gene clusters are predominantly found in soils containing high levels of calcium carbonate.

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Wu C. et al. Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria // Journal of the American Chemical Society. 2019. Vol. 141. No. 9. pp. 3910-3919.
GOST all authors (up to 50) Copy
Wu C., Shang Z., Lemetre C., Ternei M. A., Brady S. F. Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria // Journal of the American Chemical Society. 2019. Vol. 141. No. 9. pp. 3910-3919.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1021/jacs.8b12087
UR - https://doi.org/10.1021%2Fjacs.8b12087
TI - Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria
T2 - Journal of the American Chemical Society
AU - Lemetre, Christophe
AU - Wu, Changsheng
AU - Shang, Zhuo
AU - Ternei, Melinda A
AU - Brady, Sean F.
PY - 2019
DA - 2019/02/08 00:00:00
PB - American Chemical Society (ACS)
SP - 3910-3919
IS - 9
VL - 141
PMID - 30735616
SN - 0002-7863
SN - 1520-5126
ER -
BibTex |
Cite this
BibTex Copy
@article{2019_Wu
author = {Christophe Lemetre and Changsheng Wu and Zhuo Shang and Melinda A Ternei and Sean F. Brady},
title = {Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria},
journal = {Journal of the American Chemical Society},
year = {2019},
volume = {141},
publisher = {American Chemical Society (ACS)},
month = {feb},
url = {https://doi.org/10.1021%2Fjacs.8b12087},
number = {9},
pages = {3910--3919},
doi = {10.1021/jacs.8b12087}
}
MLA
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MLA Copy
Wu, Changsheng, et al. “Cadasides, Calcium-Dependent Acidic Lipopeptides from the Soil Metagenome That Are Active against Multidrug-Resistant Bacteria.” Journal of the American Chemical Society, vol. 141, no. 9, Feb. 2019, pp. 3910-3919. https://doi.org/10.1021%2Fjacs.8b12087.
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