Skip to main content
Log in

Optimal nutrient feed policies for heterologous protein production

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

RecombinantEscherichia coli, which overproduce heterologous protein, redirect endogenous metabolic activity to that mediated by the recombinant expression vector. Consequently, cells may experience perturbations in the biosynthetic reaction network, including the amino acid biosynthesis pathways. These cells are characterized by decreased growth rate, decreased cell mass yield, and increased heterologous protein degradation. This study investigates the dynamics of chloramphenicol-acetyl-transferase (CAT) synthesis and degradation inE. coli JM105 grown on minimal media, and correlates the observed phenomena with induction strength. Coordinated amino acid feeding was shown to increase the heterologous protein yield. Rational design of nutrient feeding possibilities is explored.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bentley, W. E. and Kompala, D.S. (1990),Annals of the New York Academy of Sciences 389, 121–138.

    Article  Google Scholar 

  2. Neidhardt, F. C., Ingraham, J. L., and Schaechter, M. (1990),Physiology of the Bacterial Cell: A Molecular Approach Sinauer Associates, Sunderland, MA.

    Google Scholar 

  3. Bentley, W. E. and Kompala, D.S. (1990),Biotechnology Letters 12, 329–334.

    Article  CAS  Google Scholar 

  4. Goff, S. A. and Goldberg, A. L. (1985),Cell 41, 587–595.

    Article  CAS  Google Scholar 

  5. Neidhardt, F. C., VanBogelen, R. A., and Vaughn, V. (1984),Annual Review of Genetics 18, 295–329.

    Article  CAS  Google Scholar 

  6. Phillilps, T. A., VanBogelen, R. A., and Neidhardt, F. C. (1984),Journal of Bacteriology 159, 283–287.

    Google Scholar 

  7. Lindquist, S. and Craig, E. A. (1988),Annual Review of Genetics 22, 631–677.

    Article  CAS  Google Scholar 

  8. Patrusky, B. (1990),Mosaic 21, 2–11.

    Google Scholar 

  9. Larimore, F. S., Waxman, L., and Goldberg, A. L. (1982),The Journal of Biological Chemistry 257, 4187–4195..

    CAS  Google Scholar 

  10. Grossman, A. D., Taylor, W. E., Burton, Z. F., Burgress, R. R., and Gross, C. A. (1985),Journal of Molecular Biology 186, 357–365.

    Article  CAS  Google Scholar 

  11. Mizusawa, S. and Gottesman, S. (1983),Proc. Natl. Acad. Sci. USA 80, 358–362.

    Article  CAS  Google Scholar 

  12. Chung, C. H. and Goldberg, A. L. (1981),Proc. Natl. Acad. Sci. USA 78, 4931–4935.

    Article  CAS  Google Scholar 

  13. Rodriguez, R. L. and Tait, R. E. (1983),Recombinant DNA Techniques: An Introduction, Benjamin/Cummings, Menlo Park, CA.

    Google Scholar 

  14. Ramirez, D. M. (1991), Optimal Feeding Strategies for the Production of Foreign Proteins, MS Thesis, University of Maryland, College Park, MD.

    Google Scholar 

  15. Whitney, G. K., Glick, B. R., and Robinson, C. W. (1989),Biotechnology and Bioengineering 33, 991–998.

    Article  CAS  Google Scholar 

  16. Bentley, W.E., Mirjalili, N., Anderson, D. C., Davis, R. H., and Kompala, D. S. (1990),Biotechnology and Bioengineering 35, 668–681.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harcum, S.W., Ramirez, D.M. & Bentley, W.E. Optimal nutrient feed policies for heterologous protein production. Appl Biochem Biotechnol 34, 161–173 (1992). https://doi.org/10.1007/BF02920543

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02920543

Index Entries

Navigation