4.7 Article

Dynamic model of CHO cell metabolism

期刊

METABOLIC ENGINEERING
卷 13, 期 1, 页码 108-124

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2010.09.003

关键词

Dynamic simulation; Fed-batch; Metabolic shift; Lactate metabolism; Redox metabolism

资金

  1. Pfizer (formerly Wyeth BioPharma)
  2. Tufts University
  3. NSF [0829899]

向作者/读者索取更多资源

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. (C) 2010 Elsevier Inc. All rights reserved.

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