Complementary identification of multiple flux distributions and multiple metabolic pathways

Dong Yup Lee, L. T. Fan, Sunwon Park, Yup Lee Sang, Shahram Shafie, Botond Bertók, Ferenc Friedler

Research output: Contribution to journalArticle

43 Citations (Scopus)


Cell robustness and complexity have been recognized as unique features of biological systems. Such robustness and complexity of metabolic-reaction systems can be explored by discovering, or identifying, the multiple flux distributions (MFD) and redundant pathways that lead to a given external state; however, this is exceedingly cumbersome to accomplish. It is, therefore, highly desirable to establish an effective computational method for their identification, which, in turn, gives rise to a novel insight into the cellular function. An effective approach is proposed for complementarily identifying MFD in metabolic flux analysis and multiple metabolic pathways (MMP) in structural pathway analysis. This approach judiciously integrates flux balance analysis (FBA) based on linear programming and the graph-theoretic method for determining reaction pathways. A single metabolic pathway, with the concomitant flux distribution and the overall reaction manifesting itself as the desired phenotype under some environmental conditions, is determined by FBA from the initial candidate sequence of metabolic reactions. Subsequently, the graph-theoretic method recovers all feasible MMP and the corresponding MFD. The approach's efficacy is demonstrated by applying it to the in silico Escherichia coli model under various culture conditions. The resultant MMP and MFD attaining a unique external state reveal the surprising adaptability and robustness of the intricate cellular network as a key to cell survival against environmental or genetic changes. These results indicate that the proposed approach would be useful in facilitating drug discovery.

Original languageEnglish
Pages (from-to)182-200
Number of pages19
JournalMetabolic Engineering
Issue number3
Publication statusPublished - May 1 2005


  • Flux balance analysis
  • Multiple flux distributions
  • Multiple metabolic pathways
  • P-graphs
  • Systems biology

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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