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Constraint-based flux balance analysis (FBA) has proven successful inpredicting the flux distribution of metabolic networks in diverse environmentalconditions. FBA finds one of the alternate optimal solutions that maximizes thebiomass production rate. Almaas et al have shown that the flux distributionfollows a power law, and it is possible to associate with most metabolites tworeactions which maximally produce and consume a give metabolite, respectively.This observation led to the concept of high-flux backbone (HFB) in metabolicnetworks. In previous work, the HFB has been computed using a particular optimaobtained using FBA. In this paper, we investigate the conservation of HFB of aparticular solution for a given medium across different alternate optima andnear-optima in metabolic networks of E. coli and S. cerevisiae. Using fluxvariability analysis (FVA), we propose a method to determine reactions that areguaranteed to be in HFB regardless of alternate solutions. We find that the HFBof 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 aparticular near-optima shows a large variation across alternate near-optima inboth organisms. We show that the conserved set of reactions in HFB acrossalternate near-optima has a large overlap with essential reactions andreactions which are both uniquely consuming (UC) and uniquely producing (UP).Our findings suggest that the structure of the metabolic network admits a highdegree of redundancy and plasticity in near-optimal flow patterns enhancingsystem robustness for a given environmental condition.

Conservation of high-flux backbone in alternate optimal and near-optimal flux distributions of metabolic networks