Microfiltration culture process for enhanced production of rdna receptor cells of escherichia coli

Microfiltration culture process for enhanced production of rdna receptor cells of escherichia coli

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ABSTRACT 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 In this process nutrient medium is fed continuously into an aerated and stirred fermentor, and metabolic products are withdrawn continuously at the same rate by crossflow microfiltration in an external recycle loop, so that product inhibition of cell growth is relieved.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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HIGH-THROUGHPUT MICROBIOREACTOR PROVIDES A CAPABLE TOOL FOR EARLY STAGE BIOPROCESS DEVELOPMENT Article Open access 21 January 2021 CASCADED PROCESSING ENABLES CONTINUOUS UPSTREAM PROCESSING WITH _E. COLI_ BL21(DE3) Article Open access 01 June 2021 A HIGH-DENSITY MICROFLUIDIC BIOREACTOR FOR THE AUTOMATED MANUFACTURING OF CAR T CELLS Article 04 June 2024 REFERENCES * Sortland, L.D. and Wilke, C.R. 1969. Growth of _Streptococcus faecalus_ in dense culture. _Biotechnol. Bioeng._ 11: 805–841. Article  CAS  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  * Dostálek, M. and Häggstrom, M. 1982. A filter fermentor-apparatus and control equipment. _Biotechnol. Bioeng._ 24: 2077–2086. Article  Google Scholar  * 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  * 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  * Gallup, D.M. and Gerhardt, P. 1963. Dialysis fermentor systems for concentrated culture of microorganisms. _Appl. Microbiol._ 2: 506–512. Google Scholar  * 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). * 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  * 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. * 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  * 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  * 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  * 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  * Bolivar, F. and Backman, K. 1979. Plasmids of _Escherichia coli_ as cloning vectors. _Methods Enzymol._ 68: 245–267. Article  CAS  Google Scholar  * 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  * 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  * 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  * Montgomery, R. 1961. Further studies of the phenol-sulfuric acid reagent for carbohydrates. _Biochim. Biophys. Acta._ 48: 591–593. Article  CAS  Google Scholar  * Johnson, M. 1941. Isolation and properties of a pure yeast polypeptidase. _J. Biol. Chem._ 137: 575–586. CAS  Google Scholar  * Supelco, Inc. 1975. Extraction procedures for GC analysis of culture by-products for volatile acids and alcohols. Bulletin Supplement 748G. Download references AUTHOR INFORMATION Author notes * Philipp Gerhardt: To whom correspondence should be directed. AUTHORS AND AFFILIATIONS * Department of Chemical Engineering, Michigan State University, East Lansing, MI, 48824 Kevin W. Anderson & Eric Grulke * Department of Microbiology and Public Health, Michigan State University, East Lansing, MI, 48824 Philipp Gerhardt Authors * Kevin W. Anderson View author publications You can also search for this author inPubMed Google Scholar * Eric Grulke View author publications You can also search for this author inPubMed Google Scholar * Philipp Gerhardt View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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). https://doi.org/10.1038/nbt1084-891 Download citation * Received: 19 April 1984 * Accepted: 12 June 1984 * Issue Date: 01 October 1984 * DOI: https://doi.org/10.1038/nbt1084-891 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative

ABSTRACT 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. Access through your institution Buy or subscribe This is a preview of subscription


content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print issues and online access $209.00 per year only $17.42 per issue


Learn more Buy this article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL


ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS HIGH-THROUGHPUT MICROBIOREACTOR PROVIDES


A CAPABLE TOOL FOR EARLY STAGE BIOPROCESS DEVELOPMENT Article Open access 21 January 2021 CASCADED PROCESSING ENABLES CONTINUOUS UPSTREAM PROCESSING WITH _E. COLI_ BL21(DE3) Article Open


access 01 June 2021 A HIGH-DENSITY MICROFLUIDIC BIOREACTOR FOR THE AUTOMATED MANUFACTURING OF CAR T CELLS Article 04 June 2024 REFERENCES * Sortland, L.D. and Wilke, C.R. 1969. Growth of


_Streptococcus faecalus_ in dense culture. _Biotechnol. Bioeng._ 11: 805–841. Article  CAS  Google Scholar  * 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  * 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  * 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  * 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  * 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  * 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  *


Dostálek, M. and Häggstrom, M. 1982. A filter fermentor-apparatus and control equipment. _Biotechnol. Bioeng._ 24: 2077–2086. Article  Google Scholar  * 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  * 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


  * Gallup, D.M. and Gerhardt, P. 1963. Dialysis fermentor systems for concentrated culture of microorganisms. _Appl. Microbiol._ 2: 506–512. Google Scholar  * 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). * 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  * 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. * 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  * 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  *


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  * 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  * Bolivar,


F. and Backman, K. 1979. Plasmids of _Escherichia coli_ as cloning vectors. _Methods Enzymol._ 68: 245–267. Article  CAS  Google Scholar  * 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  * 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  * 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  * Montgomery, R. 1961. Further studies of the phenol-sulfuric acid reagent for carbohydrates. _Biochim. Biophys. Acta._ 48: 591–593. Article  CAS


  Google Scholar  * Johnson, M. 1941. Isolation and properties of a pure yeast polypeptidase. _J. Biol. Chem._ 137: 575–586. CAS  Google Scholar  * Supelco, Inc. 1975. Extraction procedures


for GC analysis of culture by-products for volatile acids and alcohols. Bulletin Supplement 748G. Download references AUTHOR INFORMATION Author notes * Philipp Gerhardt: To whom


correspondence should be directed. AUTHORS AND AFFILIATIONS * Department of Chemical Engineering, Michigan State University, East Lansing, MI, 48824 Kevin W. Anderson & Eric Grulke *


Department of Microbiology and Public Health, Michigan State University, East Lansing, MI, 48824 Philipp Gerhardt Authors * Kevin W. Anderson View author publications You can also search for


this author inPubMed Google Scholar * Eric Grulke View author publications You can also search for this author inPubMed Google Scholar * Philipp Gerhardt View author publications You can


also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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). https://doi.org/10.1038/nbt1084-891 Download


citation * Received: 19 April 1984 * Accepted: 12 June 1984 * Issue Date: 01 October 1984 * DOI: https://doi.org/10.1038/nbt1084-891 SHARE THIS ARTICLE Anyone you share the following link


with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt


content-sharing initiative