Modelling the effects of glucose feeding on a recombinant E. coli fermentation

Abstract A simple unstructured model is described and compared with experimental data for fed-batch fermentations. The process studied is typical of the most common industrial recombinant fermentation in which temperature induced E. coli produces high yields of a heterologous protein (4 g met-asp-Bovine Somatotropin/l) using a complex peptone feed and a glucose feed. The model accurately predicts the effect of glucose feeding and shows that there is an optimal glucose feedrate to maximize productivity. At higher glucose feedrates, acetate levels become inhibitory and at lower levels glucose starvation occurs. The model is novel since it combines terms for acetate production and inhibition, effect of peptone feeding and temperature induction into a single relatively simple unstructured model. However the present model is unable to predict the effect of induction at different cell densities and reasons for this are suggested.

[1]  S. Carlsen,et al.  Production of recombinant human growth hormone in Escherichia coli: Expression of different precursors and physiological effects of glucose, acetate, and salts , 1990, Biotechnology and bioengineering.

[2]  J. Nielsen,et al.  Bioreaction Engineering Principles , 1994, Springer US.

[3]  Allen G. Marr,et al.  THE MAINTENANCE REQUIREMENT OF ESCHERICHIA COLI , 1963 .

[4]  J E Bailey,et al.  A kinetic model for product formation in unstable recombinant populations , 1985, Biotechnology and bioengineering.

[5]  A. G. Marr,et al.  Effect of Nutrient Concentration on the Growth of Escherichia coli , 1971, Journal of bacteriology.

[6]  A A Esener,et al.  Theory and applications of unstructured growth models: Kinetic and energetic aspects , 1983, Biotechnology and bioengineering.

[7]  J. J. Heijnen,et al.  A macroscopic model describing yield and maintenance relationships in aerobic fermentation processes , 1981 .

[8]  R. Bajpai,et al.  Control of Bacterial Fermentations , 1987, Annals of the New York Academy of Sciences.

[9]  D. Miner,et al.  A reversed-phase high-performance liquid chromatographic method for characterization of biosynthetic human growth hormone. , 1987, Analytical biochemistry.

[10]  J. Neway,et al.  Effects of medium quality on the expression of human interleukin-2 at high cell density in fermentor cultures of Escherichia coli K-12 , 1990, Applied and environmental microbiology.

[11]  Product formation during batch fermentation with recombinant Escherichia coli containing a runaway plasmid , 1992 .

[12]  G W Luli,et al.  Comparison of growth, acetate production, and acetate inhibition of Escherichia coli strains in batch and fed-batch fermentations , 1990, Applied and environmental microbiology.

[13]  Toshiomi Yoshida,et al.  Glucose feeding strategy accounting for the decreasing oxidative capacity of recombinant Escherichia coli in fed-batch cultivation for phenylalanine production , 1990 .

[14]  George Georgiou,et al.  Optimizing the production of recombinant proteins in microorganisms , 1988 .

[15]  H. Märkl,et al.  Influence of acetic acid on the growth of Escherichia coli K12 during high-cell-density cultivation in a dialysis reactor , 1997, Applied Microbiology and Biotechnology.

[16]  C. Cooney,et al.  Fermentation and Enzyme Technology , 1979 .

[17]  Patrick N. Royce,et al.  A Discussion of Recent Developments in Fermentation Monitoring and Control from a Practical Perspective , 1993 .

[18]  H. Blanch,et al.  Recombinant trypsin production in high cell density fed‐batch cultures in Escherichia coli , 1993, Biotechnology and bioengineering.