Conservation of high-flux backbone in alternate optimal and near-optimal flux distributions of metabolic networks
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Submission date: 03. Apr. 2009
published in: Systems and synthetic biology, 2 (2008) 3/4, p. 83-93
DOI number (of the published article): 10.1007/s11693-009-9025-8
PACS-Numbers: 87.18.Vf, 87.18.-h, 87.19.lw, 87.55.de, 82.39.R
Keywords and phrases: Complex Network, Flux balance analysis, Alternate optima and near-optima, Flux variability analysis, Flux plasticity
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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, for a given medium, it is possible to associate with most metabolites two reactions which maximally produce and consume a given metabolite, respectively. This observation led to the concept of high flux backbone (HFB) in metabolic networks. In previous work, the HFB was computed using a particular optima obtained from FBA. In this paper, we investigate the conservation of HFB of a particular solution 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 for growth 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 within near-optimal flow patterns for a given medium enhancing system robustness.