Global organization of metabolic fluxes in the bacterium Escherichia coli

  title={Global organization of metabolic fluxes in the bacterium Escherichia coli},
  author={Eivind Almaas and Baldvin Kovacs and Tam{\'a}s Vicsek and Zoltn Oltvai and A L Barabasi},
Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalysed biochemical reactions, is the most investigated complex intracellular web of molecular interactions. Although the topological organization of individual reactions into metabolic networks is well understood, the principles that govern their global functional use under different growth conditions raise many unanswered questions. By implementing a flux balance analysis of the… 

Identifying essential genes in Escherichia coli from a metabolic optimization principle

A constraint-based model of cellular metabolism where neither mass balance nor flux stationarity are postulated and where the relevant flux configurations optimize the global growth of the system is defined and studied.

The Activity Reaction Core and Plasticity of Metabolic Networks

Flux-balance analysis is used to thoroughly assess the activity of Escherichia coli, Helicobacter pylori, and Saccharomyces cerevisiae metabolism in 30,000 diverse simulated environments and finds that most current antibiotics interfering with bacterial metabolism target the core enzymes.

Metabolite essentiality elucidates robustness of Escherichia coli metabolism

The use of flux-sum, which is the summation of all incoming or outgoing fluxes around a particular metabolite under pseudo-steady state conditions, is reported as a good conserved property for elucidating such robustness of E. coli from the metabolite point of view.

The solution space of metabolic networks: Producibility, robustness and fluctuations

A characterization of the productive capabilities of the metabolic network of the bacterium E.coli in a specified growth medium in terms of the producible biochemical species is provided.

Optimal flux patterns in cellular metabolic networks.

Using the optimization framework of flux balance analysis, the metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia are investigated by simulating 30,000 random cellular environments.

Detecting the Significant Flux Backbone of Escherichia coli metabolism

The backbone of E. coli is disclosed, and it is found that the core of the backbones is mainly composed of reactions in energy metabolism corresponding to ancient pathways, which is useful to trace simultaneously both its evolution and adaptation fingerprints.

Evolution and Regulation of Metabolic Networks

Many experimental data support the hypothesis that the developmental pathways of cells and complex organisms are the results of conserved biological clocks based on metabolic hypercycles organized in fractal networks.

The Number of Catalytic Elements Is Crucial for the Emergence of Metabolic Cores

This analysis corroborates and expands on previous studies illustrating a crucial property of the global structure of the cellular metabolism, and offers important insights into the mechanisms which ensure the robustness and stability of living cells.

Principles of transcriptional regulation and evolution of the metabolic system in E. coli.

It is shown that enzymes controlled by the same TFs have a strong tendency to co-evolve, suggesting a significant constraint to maintain similar regulatory regimes during evolution.

Control principles of metabolic networks

An efficient computational framework for flux control is developed by introducing a complete set of flux coupling relations that helps unravel the regulatory principles of complex diseases and design novel engineering strategies at the interface of gene regulation, signaling, and metabolism.



The large-scale organization of metabolic networks

This analysis of metabolic networks of 43 organisms representing all three domains of life shows that, despite significant variation in their individual constituents and pathways, these metabolic networks have the same topological scaling properties and show striking similarities to the inherent organization of complex non-biological systems.

Metabolic Flux Ratio Analysis of Genetic and Environmental Modulations of Escherichia coli Central Carbon Metabolism

Data indicate remarkable robustness and rigidity in central carbon metabolism in the presence of genetic variation and more significant physiological changes and flux ratio differences were seen in response to altered environmental conditions.

A general definition of metabolic pathways useful for systematic organization and analysis of complex metabolic networks

This work analyzes the interplay between the pentose phosphate pathway (PPP) and glycolysis to define and comprehensively describe all metabolic routes that are both stoichiometrically and thermodynamically feasible for a group of enzymes.

Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS.

A novel methodology for rapid diagnosis of metabolic changes, which is based on probabilistic equations that relate GC-MS-derived mass distributions in proteinogenic amino acids to in vivo enzyme activities is described, providing quantitative insight into flux changes that bring about the resilience of metabolic networks to disruption.

Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA.

The presented results provide first evidence that UdhA restores the cellular redox balance by catalyzing electron transfer from NADPH to NADH.

The small world inside large metabolic networks

  • Andreas WagnerD. Fell
  • Biology
    Proceedings of the Royal Society of London. Series B: Biological Sciences
  • 2001
A graph theoretical analysis of the E. coli metabolic network is found that this network is a small–world graph, a type of graph distinct from both regular and random networks and observed in a variety of seemingly unrelated areas, such as friendship networks in sociology, the structure of electrical power grids, and the nervous system of Caenorhabditis elegans.

Metabolic Flux Responses to Pyruvate Kinase Knockout in Escherichia coli

The intracellular carbon flux distribution in wild-type and pyruvate kinase-deficient Escherichia coli was estimated using biosynthetically directed fractional 13C labeling experiments with [U-13C6]glucose, two-dimensional nuclear magnetic resonance (NMR) spectroscopy of cellular amino acids, and a comprehensive isotopomer model.

Metabolic network structure determines key aspects of functionality and regulation

A theoretical method for simultaneously predicting key aspects of network functionality, robustness and gene regulation from network structure alone is devised by determining and analysing the non-decomposable pathways able to operate coherently at steady state (elementary flux modes).

Analysis of optimality in natural and perturbed metabolic networks

The method of minimization of metabolic adjustment (MOMA), whereby the hypothesis that knockout metabolic fluxes undergo a minimal redistribution with respect to the flux configuration of the wild type is tested, is tested and found to be useful in understanding the evolutionary optimization of metabolism.

Hierarchical Organization of Modularity in Metabolic Networks

It is shown that the metabolic networks of 43 distinct organisms are organized into many small, highly connected topologic modules that combine in a hierarchical manner into larger, less cohesive units, with their number and degree of clustering following a power law.