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Incorporating metabolic flux ratios into constraint-based flux analysis by using artificial metabolites and converging ratio determinants

Paper ID Volume ID Publish Year Pages File Format Full-Text
25370 43570 2007 10 PDF Available
Title
Incorporating metabolic flux ratios into constraint-based flux analysis by using artificial metabolites and converging ratio determinants
Abstract

One of the well-established approaches for the quantitative characterization of large-scale underdetermined metabolic network is constraint-based flux analysis, which quantifies intracellular metabolic fluxes to characterize the metabolic status. The system is typically underdetermined, and thus usually is solved by linear programming with the measured external fluxes as constraints. Thus, the intracellular flux distribution calculated may not represent the true values. 13C-constrained flux analysis allows more accurate determination of internal fluxes, but is currently limited to relatively small metabolic networks due to the requirement of complicated mathematical formulation and limited parameters available. Here, we report a strategy of employing such partial information obtained from the 13C-labeling experiments as additional constraints during the constraint-based flux analysis. A new methodology employing artificial metabolites and converging ratio determinants (CRDs) was developed for improving constraint-based flux analysis. The CRDs were determined based on the metabolic flux ratios obtained from 13C-labeling experiments, and were incorporated into the mass balance equations for the artificial metabolites. These new mass balance equations were used as additional constraints during the constraint-based flux analysis with genome-scale E. coli metabolic model, which allowed more accurate determination of intracellular metabolic fluxes.

Keywords
Constraint-based flux analysis; Artificial metabolite; Converging ratio determinant (CRD); 13C-labeling experiment; Gas chromatography–mass spectrometry (GC–MS); Metabolic flux
First Page Preview
Incorporating metabolic flux ratios into constraint-based flux analysis by using artificial metabolites and converging ratio determinants
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 129, Issue 4, 10 May 2007, Pages 696–705
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering