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A Web Tool for Generating High Quality Machine-readable Biological Pathways
Published on: February 8, 2017
Superessential reactions in metabolic networks
Aditya Barve1, João Frederico Matias Rodrigues, Andreas Wagner
1Institutes of Evolutionary Biology and Environmental Studies, University of Zurich, CH-8057 Zurich, Switzerland.
Summary
A small core of 124 essential metabolic reactions is vital for organism survival across environments. This superessentiality index helps identify potential drug targets by revealing reactions that cannot be easily bypassed.
Area of Science:
- Metabolic network analysis
- Evolutionary biology
- Computational systems biology
Background:
- Organismal metabolic genotypes evolve via gene gain/loss, enabling adaptation and drug resistance.
- Pathogens can develop antimetabolic drug resistance by evolving bypass pathways.
- Understanding metabolic plasticity is key to predicting evolutionary trajectories.
Purpose of the Study:
- Quantify the bypass potential of individual metabolic reactions and enzymes.
- Identify universally essential metabolic reactions.
- Develop a metric to assess reaction bypassability for drug target identification.
Main Methods:
- Computational generation of large metabolic network ensembles.
- Ensembles synthesize all biomass components in a given environment.
- Analysis of reaction connectivity and superessentiality within network ensembles.
Main Results:
- Identified a core of 124 absolutely superessential reactions required in all networks.
- Developed a superessentiality index for thousands of reactions.
- Superessentiality index correlates with the prevalence of encoding enzymes across sequenced genomes.
Conclusions:
- A small set of metabolic reactions forms a conserved core essential for life.
- The superessentiality index is a valuable tool for identifying robust drug targets.
- Network ensemble analysis illuminates the evolution of metabolic robustness.
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