Abstract
The discovery and use of antibacterials represents a primary success of modern pharmaceutical industry. However, the pace of antibacterial discovery was heavily hindered by a series of technical difficulties and the unfavorable economics in recent years. The past decade has witnessed rapid progresses in omics and systems biology, which provided an unprecedented opportunity to accelerate the discovery of antibacterials. In this article, we first summarize the successful use of metabolic network analysis in antibacterial discovery. Then, we reveal that metabolite concentration serves as a useful criterion for selecting antimicrobial targets. The essential enzymes with low substrate concentrations (< 0.5 mM) are more druggable antibacterial targets. Besides, we find that the solubility of clinically used competitive antibacterials is at least 100 times higher than the concentrations of the competed substrates. By the new-proposed criterion, we not only identify some promising antibacterial targets but also explain some perplexing experimental observations as well.
Keywords: Antibacterial discovery, antibacterial target, bioinformatics, flux balance analysis (FBA), metabolic network, metabolite concentration, metabolomics, systems biology.
Current Computer-Aided Drug Design
Title:Metabolite Concentration as a Criterion for Antibacterial Discovery
Volume: 9 Issue: 3
Author(s): Zhong-Yi Wang, Qiang Zhu and Hong-Yu Zhang
Affiliation:
Keywords: Antibacterial discovery, antibacterial target, bioinformatics, flux balance analysis (FBA), metabolic network, metabolite concentration, metabolomics, systems biology.
Abstract: The discovery and use of antibacterials represents a primary success of modern pharmaceutical industry. However, the pace of antibacterial discovery was heavily hindered by a series of technical difficulties and the unfavorable economics in recent years. The past decade has witnessed rapid progresses in omics and systems biology, which provided an unprecedented opportunity to accelerate the discovery of antibacterials. In this article, we first summarize the successful use of metabolic network analysis in antibacterial discovery. Then, we reveal that metabolite concentration serves as a useful criterion for selecting antimicrobial targets. The essential enzymes with low substrate concentrations (< 0.5 mM) are more druggable antibacterial targets. Besides, we find that the solubility of clinically used competitive antibacterials is at least 100 times higher than the concentrations of the competed substrates. By the new-proposed criterion, we not only identify some promising antibacterial targets but also explain some perplexing experimental observations as well.
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Cite this article as:
Wang Zhong-Yi, Zhu Qiang and Zhang Hong-Yu, Metabolite Concentration as a Criterion for Antibacterial Discovery, Current Computer-Aided Drug Design 2013; 9 (3) . https://dx.doi.org/10.2174/15734099113099990030
DOI https://dx.doi.org/10.2174/15734099113099990030 |
Print ISSN 1573-4099 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6697 |
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