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

Paper ID Volume ID Publish Year Pages File Format Full-Text
31805 44840 2010 7 PDF Available
Title
Metabolite-centric approaches for the discovery of antibacterials using genome-scale metabolic networks
Abstract

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.

Keywords
Metabolite-centric approaches; Metabolite essentiality; Chokepoint analysis; Drug targeting
First Page Preview
Metabolite-centric approaches for the discovery of antibacterials using genome-scale metabolic networks
Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 12, Issue 2, March 2010, Pages 105–111
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering