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Dynamic metabolic flux analysis (DMFA): A framework for determining fluxes at metabolic non-steady state

Paper ID Volume ID Publish Year Pages File Format Full-Text
31776 44837 2011 11 PDF Available
Title
Dynamic metabolic flux analysis (DMFA): A framework for determining fluxes at metabolic non-steady state
Abstract

Metabolic flux analysis (MFA) is a key tool for measuring in vivo metabolic fluxes in systems at metabolic steady state. Here, we present a new method for dynamic metabolic flux analysis (DMFA) of systems that are not at metabolic steady state. The advantages of our DMFA method are: (1) time-series of metabolite concentration data can be applied directly for estimating dynamic fluxes, making data smoothing and estimation of average extracellular rates unnecessary; (2) flux estimation is achieved without integration of ODEs, or iterations; (3) characteristic metabolic phases in the fermentation data are identified automatically by the algorithm, rather than selected manually/arbitrarily. We demonstrate the application of the new DMFA framework in three example systems. First, we evaluated the performance of DMFA in a simple three-reaction model in terms of accuracy, precision and flux observability. Next, we analyzed a commercial glucose-limited fed-batch process for 1,3-propanediol production. The DMFA method accurately captured the dynamic behavior of the fed-batch fermentation and identified characteristic metabolic phases. Lastly, we demonstrate that DMFA can be used without any assumed metabolic network model for data reconciliation and detection of gross measurement errors using carbon and electron balances as constraints.

► New method for dynamic metabolic flux analysis (DMFA) of systems not at metabolic steady-state. ► DMFA directly fits time-series of concentration measurements to determine dynamic fluxes. ► Flux estimation is achieved without numerical integration of ODEs, or iterations. ► Characteristic metabolic phases in fermentation data are identified automatically. ► Data smoothing and estimation of average extracellular rates are unnecessary.

Keywords
DMFA, dynamic metabolic flux analysis; MFA, metabolic flux analysis; PDO, 1,3-propanediol; SSR, variance-weighted sum of squared residualsMetabolic fluxes; Dynamic analysis; Fed-batch fermentation; Process monitoring; Data reconciliation
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Dynamic metabolic flux analysis (DMFA): A framework for determining fluxes at metabolic non-steady state
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 13, Issue 6, November 2011, Pages 745–755
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us