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Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation

Paper ID Volume ID Publish Year Pages File Format Full-Text
31810 44840 2010 11 PDF Available
Title
Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation
Abstract

We have developed a reactor-scale model of Escherichia coli metabolism and growth in a 1000L process for the production of a recombinant therapeutic protein. The model consists of two distinct parts: (1) a dynamic, process specific portion that describes the time evolution of 37 process variables of relevance and (2) a flux balance based, 123-reaction metabolic model of E. coli metabolism. This model combines several previously reported modeling approaches including a growth rate-dependent biomass composition, maximum growth rate objective function, and dynamic flux balancing. In addition, we introduce concentration-dependent boundary conditions of transport fluxes, dynamic maintenance demands, and a state-dependent cellular objective. This formulation was able to describe specific runs with high-fidelity over process conditions including rich media, simultaneous acetate and glucose consumption, glucose minimal media, and phosphate depleted media. Furthermore, the model accurately describes the effect of process perturbations—such as glucose overbatching and insufficient aeration—on growth, metabolism, and titer.

Keywords
Flux balance analysis; Metabolic flux analysis; E. coli; Multiple substrate consumption; Metabolic modeling
First Page Preview
Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation
Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 12, Issue 2, March 2010, Pages 150–160
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering