Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The Interactions Between Fermentation and Protein Recovery

Bio/Technology volume 2, pages 623–627 (1984)Cite this article

Abstract

In this review we discuss the interactions between the unit operations involved in the industrial production and isolation of protein products. We consider both the interactions between the fermentation process and protein recovery, and the impacts on recovery process design resulting from the use of genetically engineered bacterial strains.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Aunstrup, K. 1979. Production, isolation, and economics of extracellular enzymes. Appl. Biochemistry & Bioengineering 2: 27–69.

    Article  CAS  Google Scholar 

  2. Lilly, M.D. 1979. Production of intracellular microbial enzymes. Appl. Biochemistry & Bioengineering 2: 1–26.

    CAS  Google Scholar 

  3. Wang, D.I.C., Cooney, C.L., Demain, A.L., Dunnill, P., Humphrey, A.E., and Lilly, M.D. 1979. p. 238–310 Fermentation & Enzyme Technology. Wiley & Sons, New York.

    Google Scholar 

  4. Scawen, M.D., Atkinson, A., and Darbyshire, J. 1980. Large-scale enzyme purification, p. 281–325. In: Applied Protein Chemistry, Grant, R.A. (ed.), Applied Science Publishers, London.

    Google Scholar 

  5. Darbyshire, J. 1981. Large scale enzyme extraction and recovery. Topics in Enzyme and Fermentation Biotechnology 5: 147–186.

    CAS  Google Scholar 

  6. Kula, M.-R., Kroner, K.H., and Hustedt, H. 1982. Purification of enzymes by liquid-liquid extraction. Adv. Biochem. Eng. 24: 73–118.

    CAS  Google Scholar 

  7. Street, G. 1983. Large scale industrial enzyme production. CRC Critical Reviews in Biotechnology 1: 59–85.

    Article  CAS  Google Scholar 

  8. Hetherington, P.J., Follows, M., Dunnill, P., and Lilly, M.D. 1971. Release of protein from baker's yeast by disruption in an industrial homogeniser. Trans. Inst. Chem. Engnrs 49: 142–148.

    CAS  Google Scholar 

  9. Follows, M., Hetherington, P.J., Dunnill, P., and Lilly, M.D. 1971. Release of enzymes from baker's yeast by disruption in an industrial homogeniser. Biotechnol. Bioeng. 13: 549–560.

    Article  CAS  Google Scholar 

  10. Limon-Lason, J., Hoare, M., Orsborn, C.B., Doyle, D.J., Dunnill, P. 1979. Reactor properties of a high-speed bead mill for microbial cell rupture. Biotechnol. Bioeng. 21: 745–774.

    Article  Google Scholar 

  11. Woodrow, J.R., and Quirk, A.V. 1982. The evaluation of the potential of a bead mill for the release of intracellular bacterial enzymes. Enzyme Microb. Technol. 4: 385–389.

    Article  Google Scholar 

  12. Schutte, H., Kroner, K.H., Hustedt, H., and Kula, M.-R. 1983. Experiences with a 20 litre industrial bead mill for the disruption of microorganisms. Enzyme Microb. Technol. 5: 143–148.

    Article  Google Scholar 

  13. Bell, D.J., Hoare, M., and Dunnill, P. 1983. The formation of protein precipitates and their centrifugal recovery. Adv. Biochem. Eng./Biotechnol. 26: 1–72.

    CAS  Google Scholar 

  14. Breslau, B.R., and Cross, R.A. 1983. An introduction to membrane separation technology. In: An Introduction to Separation Science, Karger, B.L.(ed.), Wiley & Sons, New York, to be published.

    Google Scholar 

  15. Lilly, M.D. 1981. Plenary Lecture at 1st Engineering Foundation Conference on Advances in Fermentation Recovery Process Technology. Banff, 7–12 June 1981

  16. Rosen, C.-G. 1983. Primary separation steps in fermentation processes. Proceedings of Biotech 83: 201–223.

    Google Scholar 

  17. Aunstrup, K. personal communication.

  18. Lambert, P.W., and Meers, J.L. 1983. The production of industrial enzymes. Phil. Trans. R. Soc. Lond. B300: 263–282.

    Article  Google Scholar 

  19. Savidge, T.A. 1984. Enzymatic conversions used in the production of penicillins and cephalosporins. p. 171–224. In: Biotechnology of Industrial Antibiotics, Vandamme, E. (ed.), Marcel Dekker, New York.

    Google Scholar 

  20. Pickett, A., and Haddock, B. 1983. Fermentation of recombinant organisms—problems and prospects. Proceedings of Biotech 83: 337–342.

    Google Scholar 

  21. Young, F.E., Yasbin, R.E., and Courtney, M.A. 1983. Genetic engineering of bacilli. Phil. Trans. R. Soc. Lond. B300: 241–248.

    Article  Google Scholar 

  22. Lagerlöf, E., Nathorst-Westfelt, L., Ekström, B., and Sjöberg, B. 1976. Production of 6-aminopenicillanic acid with immobilized Escherichia coli acylase. Methods in Enzymology 44: 759–768.

    Article  Google Scholar 

  23. Donaldson, T.L., Boonstra, E.F., and Hammond, J.M. 1980. Kinetics of protein denaturation at gas-liquid interfaces. J. Colloid Interface Sci. 74: 441–450.

    Article  CAS  Google Scholar 

  24. Virkar, P.D., Narendaranathan, T.J., Hoare, M., and Dunnill, P. 1981. Studies of the effects of shear on globular proteins: extension to high shear fields and pumps. Biotechnol. Bioeng. 23: 425–429.

    Article  CAS  Google Scholar 

  25. Matteo, C.C., Glade, M., Tanaka, A., Piret, J., and Demain, A.L. 1975. Microbiological studies on the formation of gramicidin S synthetases. Biotechnol. Bioeng. 17: 129–142.

    Article  CAS  Google Scholar 

  26. Gray, P.P., Dunnill, P., and Lilly, M.D. 1972. The continuous-flow isolation of enzymes. Proceedings IV Intnl. Ferm. Symp.: Fermentation Technology Today: 347–351.

  27. Higgins, J.J., Lewis, D.J., Daly, W.H., Mosqueira, F.G., Dunnill, P., and Lilly, M.D. 1978. Investigation of the unit operations involved in the continuous flow isolation of β-galactosidase from Escherichia coli . Biotechnol. Bioeng. 20: 159–182.

    Article  CAS  Google Scholar 

  28. Fish, N.M. 1979. Microbial enzyme hydroxylation of n-nonane. Ph.D. Thesis, University of London

    Google Scholar 

  29. Augenstein, D.C., Thrasher, K., Sinskey, A.J., and Wang, D.I.C. 1974. Optimization in the recovery of a labile intracellular enzyme. Biotechnol. Bioeng. 16: 1433–1447.

    Article  CAS  Google Scholar 

  30. Buckland, B.C., Richmond, W., Dunnill, P., and Lilly, M.D. 1974. The large-scale isolation of intracellular microbial enzymes: cholesterol oxidase from Nocardia . p. 65–79. In: Industrial Aspects of Biochemistry, Spencer, B. (ed.), FEES, Amsterdam.

    Google Scholar 

  31. Engler, C.R., and Robinson, C.W. 1981. Disruption of Candida utilis cells in high pressure flow devices. Biotechnol. Bioeng. 23: 765–780.

    Article  Google Scholar 

  32. Nesaratnam, S.T., Wase, D.A.J., and Blakebrough, N. 1982. The susceptibility to ultrasonic disintegration of Klebsiella pneumoniae NCTC 418. Eur. J. Appl. Microbiol. Biotechnol. 15: 56–58.

    Article  CAS  Google Scholar 

  33. Buckland, B.C., Lilly, M.D., and Dunnill, P. 1976. The kinetics of cholesterol oxidase synthesis by Nocardia rhodocrous . Biotechnol. Bioeng. 18: 601–621.

    Article  CAS  Google Scholar 

  34. Brookes, I. unpublished results.

  35. Fish, N.M., Harbron, S., Allenby, D.J., and Lilly, M.D. 1983. Oxidation of n-alkanes: isolation of alkane hydroxylase from Pseudrimonas putida . Eur. J. Appl. Microbiol. Biotechnol. 17: 57–63.

  36. Asenjo, J.A. 1981. Process for the production of yeast-lytic enzymes and the disruption of whole yeast cells. Advances in Biotechnology 3: 295–300.

    CAS  Google Scholar 

  37. Russell, A.J. 1981. The production and purification of salicylate hydroxylase from a Pseudomonad . Ph.D. Thesis, University of London.

  38. Cheng, Y.-S.E., Kwoh, D.Y., Kwoh, J., Soltvedt, B.C., and Zipser, D. 1981. Stabilization of a degradable protein by its overexpression in Escherichia coli . Gene 14: 121–130.

    Article  CAS  Google Scholar 

  39. Wetlaufer, D.B. 1981. Folding of protein fragments. Adv. Protein Chem. 34: 61–92.

    Article  CAS  Google Scholar 

  40. Ghelis, C., and Yon, J., 1982. Protein Folding. Academic Press, New York.

    Google Scholar 

  41. Cornelis, P., Digneffe, C., and Willemot, K. 1982. Cloning and expression of a Bacillus coagulans amylase gene in Escherichia coli . Mol. Gen. Genet. 186: 507–511.

    Article  CAS  Google Scholar 

  42. Kato, C., Kudo, T., Watanabe, K., and Horikoshi, K. 1983. Extracellular production of Bacillus penicillinase by Escherichia coli pEAP2. Eur. J. Appl. Microbiol. Biotechnol. 18: 339–343.

    Article  CAS  Google Scholar 

  43. Gray, G.L., McKeown, K.A., Jones, A.J.S., Seeburg, P.H., and Heyneker, H.L. 1984. Pseudomonas aeruginosa secretes and correctly processes human growth hormone. Bio/Technology 2: 161–165.

    CAS  Google Scholar 

  44. Palva, L., Lehtovaara, P., Kääriäinen, L., Sibakov, M., Cantell, K., Schein, C. H., Kashiwagi, K., and Weissmann, C. 1983. Secretion of interferon by Bacillus subtilis . Gene 22: 229–235.

    Article  CAS  Google Scholar 

  45. Palva, L., Sarvas, M., Lehtovaara, P., Sibakov, M., and Kääriäinen, L. 1982. Secretion of Escherichia coli β-lactamase from Bacillus subtilis by the aid of α-amylase signal sequence. Proc. Natl. Acad. Sci. USA. 79: 5582–5586.

    Article  CAS  Google Scholar 

  46. Hitzeman, R.A., Leung, D.W., Perry, J., Kohr, W.J., Levine, H.L., and Goeddel, D.V. 1983. Secretion of human interferons by yeast. Science 219: 620–625.

    Article  CAS  Google Scholar 

  47. Rothstein, S.J., Lazarus, C.M., Smith, W.E., Baulcombe, D.C., and Gatenby, A.A. 1984. Secretion of a wheat α-amylase expressed in yeast. Nature (London) 308: 662–665.

    Article  CAS  Google Scholar 

  48. Switzer, R.L. 1977. The inactivation of microbial enzymes in vivo. Ann. Rev. Microbiol. 31: 135–157.

    Article  CAS  Google Scholar 

  49. Goldberg, A.L., and St. John, A.C. 1976. Intracellular protein degradation in mammalian and bacterial cells: part 2. Ann. Rev. Biochem. 45: 747–803.

    Article  CAS  Google Scholar 

  50. Itakura, K., Hirose, T., Crea, R., Riggs, A.D., Heyneker, H.L., Bolivar, F., and Boyer, H.W. 1977. Expression in Escherichia coli of a chemically synthesized gene for the hormone somatostatin. Science 198: 1056–1063.

    Article  CAS  Google Scholar 

  51. Goeddel, D.V., Heyneker, H.L., Hozumi, T., Arentzen, R., Itakura, K., Yansura, D.G., Ross, M.J., Miozzari, G., Crea, R., and Seeburg, P.H. 1979. Direct expression in Escherichia coli of a DNA sequence coding for human growth hormone. Nature (London) 281: 544–548.

    Article  CAS  Google Scholar 

  52. Charette, M.F., Henderson, G.W., and Markovitz, A. 1981. ATP hydrolysis-dependent protease activity of the Ion (capR) protein of Escherichia coli K-12. Proc. Natl. Acad. Sci. USA. 78: 4728–4732.

    Article  CAS  Google Scholar 

  53. Chung, C.H., and Goldberg, A.L. 1981. The product of the lon (capR) gene in Escherichia coli is the ATP-dependent protease, protease La. Proc. Natl. Acad. Sci. USA. 78: 4931–4935.

    Article  CAS  Google Scholar 

  54. Shineberg, B., and Zipser, D., 1973. The lon gene and degradation of β-galactosidase nonsense fragments. J. Bacteriol. 116: 1469–1471.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Gottesman, S., and Zipser, D. 1978. Deg phenotype of Escherichia coli lon mutants. J. Bacteriol. 133: 844–851.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Simon, L.D., Randolph, B., Irwin, N., and Binkowski, G. 1983. Stabilization of proteins by a bacteriophage T4 gene cloned in Escherichia coli . Proc. Natl. Acad. Sci. 80: 2059–2062.

    Article  CAS  Google Scholar 

  57. Sassenfeld, H.M., and Brewer, S.J. 1984. A polypeptide fusion designed for the purification of recombinant proteins. Bio/Technology 2: 76–81.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemical and Biochemical Engineering, University College London, Torrington Place, London, WC1E 7JE, U.K.

    Neville M. Fish & Malcolm D. Lilly

Authors
  1. Neville M. Fish
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Malcolm D. Lilly
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fish, N., Lilly, M. The Interactions Between Fermentation and Protein Recovery. Nat Biotechnol 2, 623–627 (1984). https://doi.org/10.1038/nbt0784-623

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0784-623

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing