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Dynamic model of CHO cell metabolism

Paper ID Volume ID Publish Year Pages File Format Full-Text
31840 44842 2011 17 PDF Available
Title
Dynamic model of CHO cell metabolism
Abstract

Fed-batch cultures are extensively used for the production of therapeutic proteins. However, process optimization is hampered by lack of quantitative models of mammalian cellular metabolism in these cultures. This paper presents a new kinetic model of CHO cell metabolism and a novel framework for simulating the dynamics of metabolic and biosynthetic pathways of these cells grown in fed-batch culture. The model defines a subset of the intracellular reactions with kinetic rate expressions based on extracellular metabolite concentrations and temperature- and redox-dependent regulatory variables. The simulation uses the rate expressions to calculate pseudo-steady state flux distributions and extracellular metabolite concentrations at discrete time points. Experimental data collected in this study for several different CHO cell fed-batch cultures are used to derive the rate expressions, fit the parameters, and validate the model. The simulations accurately predicted the effects of process variables, including temperature shift, seed density, specific productivity, and nutrient concentrations.

Keywords
Dynamic simulation; Fed-batch; Metabolic shift; Lactate metabolism; Redox metabolism
First Page Preview
Dynamic model of CHO cell metabolism
Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 13, Issue 1, January 2011, Pages 108–124
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering