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Conservation of high-flux backbone in alternate optimal and near-optimal flux distributions of metabolic networks
Constraint-based flux balance analysis (FBA) has proven successful in
predicting the flux distribution of metabolic networks in diverse environmental
conditions. FBA finds one of the alternate optimal solutions that maximizes the
biomass production rate. Almaas et al have shown that the flux distribution
follows a power law, and it is possible to associate with most metabolites two
reactions which maximally produce and consume a give metabolite, respectively.
This observation led to the concept of high-flux backbone (HFB) in metabolic
networks. In previous work, the HFB has been computed using a particular optima
obtained using FBA. In this paper, we investigate the conservation of HFB of a
particular solution for a given medium across different alternate optima and
near-optima in metabolic networks of E. coli and S. cerevisiae. Using flux
variability analysis (FVA), we propose a method to determine reactions that are
guaranteed to be in HFB regardless of alternate solutions. We find that the HFB
of a particular optima is largely conserved across alternate optima in E. coli,
while it is only moderately conserved in S. cerevisiae. However, the HFB of a
particular near-optima shows a large variation across alternate near-optima in
both organisms. We show that the conserved set of reactions in HFB across
alternate near-optima has a large overlap with essential reactions and
reactions which are both uniquely consuming (UC) and uniquely producing (UP).
Our findings suggest that the structure of the metabolic network admits a high
degree of redundancy and plasticity in near-optimal flow patterns enhancing
system robustness for a given environmental condition.Comment: 11 pages, 6 figures, to appear in Systems and Synthetic Biolog
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