Summary
A variety of feeding strategies have been described for attaining high cell densities in fed-batch fermentors. Although cell density is an important component in the produtivity of recombinant fermentations, it must be achievable with high product expression levels. Experiments were conducted to study the influence of fermentation feeding strategies on the production of a recombinant malaria antigen inEscherichia coli. C-source feeding profiles were calculated to maintain specific growth rates at 0.1, 0.2, 0.35, and 0.5 l/h prior to induction in defined and complex media using an exponential growth model. Fed-batch fermentations employing these feeding profiles effectively controlled the specific growth rates prior to induction. Antigen yields per dry cell weight did not vary with specific growth rate. Antigen yields from fed-batch fermentations achieving high cell densities were similar to batch fermentations achieving low cell densities. These results show that C-feeding policies can limit growth without reducing expression levels in some systems, and suggest applications in managing oxygen demand and catabolic by-product formation during process scale-up.
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Barnes, D.R., D.E. Reilly and D. Sternberg. 1983. Utilization of carbon byE. coli in fed-batch, high density fermentations. Paper presented at the 186th National Meeting of the American Chemical Society, August 28–September 2, 1983, Washington, D.C.
Bauer, S. and J. Shiloach. 1974. Maximal exponential growth rate and yield ofE. coli obtainable in a bench-scale fermentor. Biotechnol. Bioeng. 16: 933–941.
Bauer, S. and M.D. White. 1976. Pilot scale exponential growth ofEscherichia coli W to high cell concentration with temperature variation. Biotechnol. Bioeng. 18: 839–846.
Fieschko, J. and T. Ritch. 1986. Production of human alpha consensus interferon in recombinantEscherichia coli. Chem. Eng. Commun. 45: 229–240.
Gleiser, I.E. and S. Bauer. 1981. Growth ofE. coli W to high cell concentration by oxygen level linked control of carbon source concentration. Biotechnol. Bioeng. 23: 1015–1021.
Johnson, A. 1986. The control of fermentation processes. In: Modelling and Control of Biotechnological Processes—Proceedings of the 1st IFAC Symposium (Johnson, A. ed.), pp. 1–12, Pergamon Press, Oxford.
Luli, G.W., L.B. Gordon and B.R. Allen. 1985. A gradientfeed process for obtaining high cell densities with reduced acid production forEscherichia coli. Paper presented at the 190th National Meeting of the American Chemical Society, September 10, 1985, Chicago.
Ravetch, J.V., J. Young and G. Poste. 1986. Molecular genetic strategies for the development of anti-malarial vaccines. Biotechnology 3: 729–740.
Shatzman, A., Y.S.Ho and M. Rosenberg. 1983. Use of phage λ regulatory signals to obtain efficient expression of genes inEscherichia coli. Methods Enzymol. 101: 123–138.
Shiloach, J. and S. Bauer. 1975. High-yield growth ofE. coli at different temperatures in a bench scale fermentor. Biotechnol. Bioeng. 17: 227–239.
Siegel, R. and D.Y. Ryu. 1985. Kinetic study of instability of recombinent plasmid pPLc23trpAl inE. coli using two-stage continuous culture system. Biotechnol. Bioeng. 27: 28–33.
Suzuki, T., H. Mori, T. Yamane and S. Shimizu. 1985. Automatic supplementation of minerals in fed-batch culture to high cell mass concentration. Biotechnol. Bioeng. 27: 192–201.
Young, J.F., W.T. Hockmeyer, M. Gross, W.R. Ballou, R.A. Wirtz, J.H. Trosper, R.L. Beaudoin, M.R.Hollingdale, L.H. Miller, C.L. Diggs and M. Rosenberg. 1985. Expression ofPlasmodium falciparum circumsporozoite proteins inEscherichia coli for potential use in a human malaria vaccine. Science 228: 958–962.
Zabriskie, D.W. and E. Arcuri. 1986. Factors influencing productivity of fermentations employing recombinant microorganisms. Enzyme Microb. Technol. 8: 705–776.
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Zabriskie, D.W., Wareheim, D.A. & Polansky, M.J. Effects of fermentation feeding strategies prior to induction of expression of a recombinant malaria antigen inEscherichia coli . Journal of Industrial Microbiology 2, 87–95 (1987). https://doi.org/10.1007/BF01569507
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DOI: https://doi.org/10.1007/BF01569507