Abstract
The in vivo measurement of metabolic flux by 13C-based metabolic flux analysis (13C-MFA) provides valuable information regarding cell physiology. Bioinformatics tools have been developed to estimate metabolic flux distributions from the results of tracer isotopic labeling experiments using a 13C-labeled carbon source. Metabolic flux is determined by nonlinear fitting of a metabolic model to the isotopic labeling enrichment of intracellular metabolites measured by mass spectrometry. Whereas 13C-MFA is conventionally performed under isotopically constant conditions, isotopically nonstationary 13C metabolic flux analysis (INST-13C-MFA) has recently been developed for flux analysis of cells with photosynthetic activity and cells at a quasi-steady metabolic state (e.g., primary cells or microorganisms under stationary phase). Here, the development of a novel open source software for INST-13C-MFA on the Windows platform is reported. OpenMebius (Open source software for Metabolic flux analysis) provides the function of autogenerating metabolic models for simulating isotopic labeling enrichment from a user-defined configuration worksheet. Analysis using simulated data demonstrated the applicability of OpenMebius for INST-13C-MFA. Confidence intervals determined by INST-13C-MFA were less than those determined by conventional methods, indicating the potential of INST-13C-MFA for precise metabolic flux analysis. OpenMebius is the open source software for the general application of INST-13C-MFA.
Highlights
The in vivo measurement of metabolic flux by 13C-based metabolic flux analysis (13C-MFA) provides valuable information regarding cell physiology in fields ranging from the metabolic engineering of microorganisms to the analysis of human metabolic diseases [1,2,3]
Labeled molecule and one nonlabeled molecule of Ala are generated from one molecule of [1-13C] glucose by the EMP pathway, no 13C-labeled Ala is produced via the PP pathway, because the 13C atom is metabolically discarded as CO2
OpenMebius is a toolbox for conventional 13C-MFA and INST-13C-MFA using mass spectrometry data implemented in MATLAB on the Windows platform
Summary
The in vivo measurement of metabolic flux by 13C-based metabolic flux analysis (13C-MFA) provides valuable information regarding cell physiology in fields ranging from the metabolic engineering of microorganisms to the analysis of human metabolic diseases [1,2,3]. Since metabolic fluxes are estimated by a computational analysis of the isotopic labeling data produced by a series of wet experiments [4,5,6,7], the development of an open software platform for 13C-MFA is desired for further methodology improvement and wider applications for in vivo metabolic flux measurement. Labeled molecule and one nonlabeled molecule of Ala are generated from one molecule of [1-13C] glucose by the EMP pathway, no 13C-labeled Ala is produced via the PP pathway, because the 13C atom is metabolically discarded as CO2. The metabolic flux ratio between the EMP and PP pathways could be estimated from the relative abundances of 13C-
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