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Microfiltration Culture Process for Enhanced Production of rDNA Receptor Cells of Escherichia Coli


A novel microfiltration batch culture process, suitable for scale-up, has been designed, instrumented, and studied with a representative recombinant-DNA receptor strain of Escherichia coli. In this process nutrient medium is fed continuously into an aerated and stirred fermentor, and metabolic products are withdrawn continuously at the same rate by crossflow microfiltration in an external recycle loop, so that product inhibition of cell growth is relieved. The maximum density of cells is increased fivefold more than in the control process, and is limited by acetic and other organic acids accumulating from the aerobic fermentation of excess glucose.

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  1. Sortland, L.D. and Wilke, C.R. 1969. Growth of Streptococcus faecalus in dense culture. Biotechnol. Bioeng. 11: 805–841.

    Article  CAS  Google Scholar 

  2. Schultz, J.S. and Gerhardt, P. 1969. Dialysis culture of microorganisms: design, theory, and results. Bacteriol. Rev. 33: 1–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Stieber, R.W. and Gerhardt, P. 1981. Dialysis continuous process for ammonium lactate fermentation: simulated and experimental dialy-sate-feed, immobilized-cell systems. Biotechnol. Bioeng. 23: 535–549.

    Article  CAS  Google Scholar 

  4. Kyung, K.H. and Gerhardt, P. 1984. Continuous production of ethanol by yeast “immobilized” in a membrane-contained fermentor. Biotechnol. Bioeng. 26: 252–256.

    Article  CAS  Google Scholar 

  5. Pirt, S.J. and Kurowski, W.M. 1970. An extension of the theory of the chemostat with feedback of organisms. Its experimental realization with a yeast culture. J. Gen. Microbiol. 63: 357–366.

    Article  CAS  Google Scholar 

  6. Watson, D.C. and Berry, D.R. 1979. Use of an exchange nitration technique to obtain synchronous sporulation in an extended batch fermentation. Biotechnol. Bioeng. 21: 213–220.

    Article  Google Scholar 

  7. Rogers, P.L., Lee, K.J., Skotnicki, M.L. and Tribe, D.E. 1982. Ethanol production by Zymomonas mobilis. Adv. Biochem. Eng. 23: 37–84.

    Google Scholar 

  8. Dostálek, M. and Häggstrom, M. 1982. A filter fermentor-apparatus and control equipment. Biotechnol. Bioeng. 24: 2077–2086.

    Article  Google Scholar 

  9. Charley, R.C., Fein, J.E., Lavers, B.H., Lawford, H.G. and Lawford, G.R. 1983. Optimization of process design for continuous ethanol production by Zymomonas mobilis ATCC 29191. Biotechnol. Letters 5: 169–174.

    Article  CAS  Google Scholar 

  10. Janssens, J.H., Bernard, A. and Bailey, R.B. 1984. Ethanol from whey: continuous fermentation with cell recycle. Biotech. Bioeng. 26: 1–5.

    Article  CAS  Google Scholar 

  11. Gallup, D.M. and Gerhardt, P. 1963. Dialysis fermentor systems for concentrated culture of microorganisms. Appl. Microbiol. 2: 506–512.

    Google Scholar 

  12. Stieber, R.W. 1979. Dialysis continuous processes for microbial fermentations: mathematical models, computer simulations, and experimental tests. Michigan State University, E. Lansing, Mich. (Ph. D. thesis).

  13. Tanny, G.B., Mirelman, D. and Pistole, F. 1980. Improved filtration technique for concentrating and harvesting bacteria. Appl. Environ. Microbiol. 40: 269–273.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Anderson, K.W., Grulke, E.A. and Gerhardt, P. 1984. Liquid level control in an aerated continuous flow fermenter. Paper presented at the 188th National Meeting of the American Chemical Society, Division of Microbial and Biochemical Technology, Phil. PA, 26–31 August, 1984.

  15. Amarasingham, C.R. and Davis, B.D. 1965. Regulation of α-ketoglutarate dehydrogenase formation in Esherichia coli. J. Biol. Chem. 240: 3664–3668.

    CAS  PubMed  Google Scholar 

  16. Doelle, H.W., Hollywood, N. and Westwood, A.W. 1974. Effect of glucose concentration on a number of enzymes involved in the aerobic and anaerobic utilization of glucose in turbidostat cultures of Escherichia coli. Microbios 9: 221–232.

    CAS  PubMed  Google Scholar 

  17. Hollywood, N. and Doelle, H.W. 1976. Effect of specific growth rate and glucose concentration on growth and glucose metabolism of Escherichia coli K-12. Microbios 17: 23–33.

    CAS  PubMed  Google Scholar 

  18. Doelle, H.W., Ewings, K.N. and Hollywood, N.W. 1982. Regulation of glucose metabolism in bacterial systems. Adv. Biochem. Eng. 23: 1–35.

    CAS  Google Scholar 

  19. Bolivar, F. and Backman, K. 1979. Plasmids of Escherichia coli as cloning vectors. Methods Enzymol. 68: 245–267.

    Article  CAS  Google Scholar 

  20. Boyer, H.W. and Roulland-Dussoix, D. 1969. A complementation analysis of the restriction and modification of DNA in Escherichia coli. J. Mol. Biol. 41: 459–472.

    Article  CAS  Google Scholar 

  21. Dubois, M., Gilles, K.A., Hamilton, J.K., Rebers, P.A. and Smith, F. 1956. Colorimetric method for determination of sugars and related substances. Anal. Chem. 28: 350–356.

    Article  CAS  Google Scholar 

  22. Johnson, R.R., Balwani, T.L., Johnson, L.J., McClure, K.E. and Dehority, B.A. 1966. Corn plant maturity. II. Effects on in vitro cellulose digestability and soluble carbohvdrate content. J. Animal Sci. 25: 617–623.

    Article  CAS  Google Scholar 

  23. Montgomery, R. 1961. Further studies of the phenol-sulfuric acid reagent for carbohydrates. Biochim. Biophys. Acta. 48: 591–593.

    Article  CAS  Google Scholar 

  24. Johnson, M. 1941. Isolation and properties of a pure yeast polypeptidase. J. Biol. Chem. 137: 575–586.

    CAS  Google Scholar 

  25. Supelco, Inc. 1975. Extraction procedures for GC analysis of culture by-products for volatile acids and alcohols. Bulletin Supplement 748G.

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Anderson, K., Grulke, E. & Gerhardt, P. Microfiltration Culture Process for Enhanced Production of rDNA Receptor Cells of Escherichia Coli. Nat Biotechnol 2, 891–896 (1984).

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