Prediction of metabolic fluxes by incorporating genomic context and flux-converging pattern analyses

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Flux balance analysis (FBA) of a genome-scale metabolic model allows calculation of intracellular fluxes by optimizing an objective function, such as maximization of cell growth, under given constraints, and has found numerous applications in the field of systems biology and biotechnology. Due to the underdetermined nature of the system, however, it has limitations such as inaccurate prediction of fluxes and existence of multiple solutions for an optimal objective value. Here, we report a strategy for accurate prediction of metabolic fluxes by FBA combined with systematic and condition-independent constraints that restrict the achievable flux ranges of grouped reactions by genomic context and flux-converging pattern analyses. Analyses of three types of genomic contexts, conserved genomic neighborhood, gene fusion events, and co-occurrence of genes across multiple organisms, were performed to suggest a group of fluxes that are likely on or off simultaneously. The flux ranges of these grouped reactions were constrained by flux-converging pattern analysis. FBA of the Escherichia coli genome-scale metabolic model was carried out under several different genotypic (pykF, zwf, ppc, and sucA mutants) and environmental (altered carbon source) conditions by applying these constraints, which resulted in flux values that were in good agreement with the experimentally measured (13)C-based fluxes. Thus, this strategy will be useful for accurately predicting the intracellular fluxes of large metabolic networks when their experimental determination is difficult.
Publisher
NATL ACAD SCIENCES
Issue Date
2010-08
Language
English
Article Type
Article
Keywords

ESCHERICHIA-COLI K-12; IN-SILICO MODELS; GENE KNOCKOUT; C-13-LABELING EXPERIMENTS; CORYNEBACTERIUM-GLUTAMICUM; ENZYME-ACTIVITIES; NETWORK; TRANSCRIPTOME; RECONSTRUCTIONS; MICROORGANISMS

Citation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.107, no.33, pp.14931 - 14936

ISSN
0027-8424
DOI
10.1073/pnas.1003740107
URI
http://hdl.handle.net/10203/23321
Appears in Collection
CBE-Journal Papers(저널논문)
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