Understanding the system-level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches, such as constraint-based fluxbalance analysis, have proved highly successful in analyzing the capabilities of cellular metabolism, including its capacity to predict deletion phenotypes, the ability to calculate the relative flux values of metabolic reactions, and the capability to identify properties of optimal growth states. Here, we use flux-balance analysis to thoroughly assess the activity of Escherichia coli, Helicobacter pylori, and Saccharomyces cerevisiae metabolism in 30,000 diverse simulated environments. We identify a set of metabolic reactions forming a connected metabolic core that carry non-zero fluxes under all growth conditions, and whose flux variations are highly correlated. Furthermore, we find that the enzymes catalyzing the core reactions display a considerably higher fraction of phenotypic essentiality and evolutionary conservation than those catalyzing noncore reactions. Cellular metabolism is characterized by a large number of species-specific conditionally active reactions organized around an evolutionary conserved, but always active, metabolic core. Finally, we find that most current antibiotics interfering with bacterial metabolism target the core enzymes, indicating that our findings may have important implications for antimicrobial drug-target discovery.
metabolic networks, flux-balance analysis (FBA), activity reaction core
PLoS Computational Biology
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
© 2010 Almaas et al.
Almaas, Eivind; Oltvai, Zoltán N.; and Barabási, Albert-László, "The activity reaction core and plasticity of metabolic networks" (2005). Physics Faculty Publications. Paper 102. http://hdl.handle.net/2047/d20000675
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