Metabolite-centric approaches for the discovery of antibacterials using genome-scale metabolic networks

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Development of genome-scale metabolic models and various constraints-based flux analyses have enabled more sophisticated examination of metabolism. Recently reported metabolite essentiality studies are also based on the constraints-based modeling, but approaches metabolism from a metabolite-centric perspective, providing synthetic lethal combination of reactions and clues for the rational discovery of antibacterials. In this study, metabolite essentiality analysis was applied to the genome-scale metabolic models of four microorganisms: Escherichia coli, Helicobacter pylori, Mycobacterium tuberculosis and Staphylococcus aureus. Furthermore, chokepoints, metabolites surrounded by enzymes that uniquely consume and/or produce them, were also calculated based on the network properties of the above organisms. A systematic drug targeting strategy was developed by combining information from these two methods. Final drug target metabolites are presented and examined with knowledge from the literature. (C) 2009 Elsevier Inc. All rights reserved.
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Issue Date
2010-03
Language
English
Article Type
Article
Citation

METABOLIC ENGINEERING, v.12, no.2, pp.105 - 111

ISSN
1096-7176
DOI
10.1016/j.ymben.2009.05.004
URI
http://hdl.handle.net/10203/19784
Appears in Collection
CBE-Journal Papers(저널논문)
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