Scale-up of microbial processes: Impacts, tools and open questions

Journal of Biotechnology

Volumn 160, Issue 1-2, 2012, Pages 3-9

  Takors, R ^a  

^a UNIVERSITY OF STUTTGART   (Germany)

Author keywords

Bioprocesses; Scale up

Indexed keywords

BIOPROCESSES; BIOTECH INDUSTRY; BIOTECHNOLOGICAL PRODUCTION; ENVIRONMENTAL HETEROGENEITY; LARGE SCALE PRODUCTIONS; MICROBIAL PROCESS; PRODUCTION SCALE; RESEARCH RESULTS; SCALE-UP; TOOL DEVELOPMENT;

BIOTECHNOLOGY;

BIOLOGICAL FACTOR; CHEMICAL FACTOR; UNCLASSIFIED DRUG;

ARTICLE; BIOENGINEERING; BIOPROCESS; BIOREACTOR; BIOTECHNOLOGY; CONTROLLED STUDY; INDUSTRIAL PRODUCTION; LARGE SCALE PRODUCTION; MICROBIAL KINETICS; MICROENVIRONMENT; PRIORITY JOURNAL; SCALE UP;

BACTERIAL PHYSIOLOGICAL PHENOMENA; BIOREACTORS; BIOTECHNOLOGY; FUNGI; INDUSTRIAL MICROBIOLOGY;

EID: 84862167117     PISSN: 01681656     EISSN: 18734863     Source Type: Journal    
DOI: 10.1016/j.jbiotec.2011.12.010     Document Type: Article

References (84)

1. Aboka F.O., Yang H., de Jonge L.P., van Winden W.A., van Gulik W.M., Oudshorn A., Heijnen J.J. Characterization of an experimental miniature bioreactor for cellular perturbation studies. Biotechnol. Bioeng. 2006, 95:1032-1042.
2. Amanullah A., McFarlane C.M., Emery A.N., Nienow A.W. Scale-down model to simulate spatial pH variations in large-scale bioreactors. Biotechnol. Bioeng. 2001, 73(5):390-399.
3. Asenjo, J.A., Merchuk, J.C., 1995. Bioreactor system design. Marcel Dekker Inc., ISBN-0-8247-9002-2.
4. Augé, C., 2000. Scale-down Untersuchungen mit Corynebacterium glutamicum in verschiedenen Reaktorsystemen mittels Durchflusszytometrie und Nebenproduktanalyse, Diplomarbeit, Fakultät Verfahrenstechnik, Universität Stuttgart.
5. Baez A., Flores N., Bolivar F., Ramirez O.T. Metabolic and transcriptional response of recombinant Escherichia coli to elevated dissolved carbon dioxide concentrations. Biotechnol. Bioeng. 2009, 104(1):102-110.
6. 2 gradients in scale-down system: a metabolic and transcriptional study of recombinant Escherichia coli. Biotechnol. J. 2011, 6(8):959-967.
7. Buziol S., Bashir I., Baumeister A., Claassen W., Noisommit-Rizzi N., Mailinger W., Reuss M. New bioreactor-coupled rapid stopped flow sampling technique for measurements of metabolite dynamics on subsecond time scale. Biotechnol. Bioeng. 2002, 80:632-636.
8. Buziol S., Warth L., Magario I., Freund A., Siemann-Herzberg M., Reuss M. Dynamic response of the expression of hxt1, hxt5, hxt7 transport proteins in Saccharomyces cerevisiae to perturbations in the extracellular glucose concentration. J. Biotechnol. 2007, 134:203-210.
9. Bylund F., Collet E., Enfors S.O., Larsson G. Substrate gradient formation in the large-scale bioreactor lowers cell yield and increases by-product formation. Bioproc. Eng. 1998, 18:171-180.
10. Bylund F., Guillard F., Enfors S.O., Träggardh C., Larsson G. Scale down of recombinant protein production: a comparative study of scaling performance. Bioproc. Eng. 1999, 20:377-389.
11. De Jonge L.P., Buijs N.A.A., ten Pierick A., Deshmukh A., Zhao Z., Kiel J.A.K.W., Heijnen J.J., van Gulik W.M. Scale-down of penicillin production in Penicillium chrysogenum. Biotechnol. J. 2011, 6(8):944-958.
12. Delvigne F., Boxus M., Ingels S., Thonart P. Bioreactor mixing efficiency modulates the activity of prpoS::GFP reporter gene in E. coli. Microbial Cell Fac. 2009, 8(15). 10.1186/1475-2859-8-15.
13. Delvigne F., Ingels S., Thonart P. Evaluation of a set of E. coli reporter strains as physiological tracer for estimating bioreactor efficiency. Proc. Biochem. 2010, 45:1769-1778.
14. Delvigne F., Brognaux A., Gorret N., Neubauer P., Delafosse A., Collignon M.-L., Toye D., Boxus M., Thonart P. Characterization of the response of GFP microbial biosensors sensitive to substrate limitation in scale-down bioreactors. Biochem. Eng. J. 2011, 55:131-139.
15. 13C labeling based metabolic flux analysis and l-lysine production. Metab. Eng. 2003, 5:96-107.
16. El Massaoudi M., Spelthahn J., Drysch A., de Graaf A.A., Takors R. Production process monitoring by serial mapping of microbial carbon flux distributions using a novel sensor reactor approach: part I: sensor reactor system. Metab. Eng. 2003, 5:86-95.
17. Enfors S.O., Jahic M., Roskov A., Xu B., Hecker M., Jürgen B., Krüger E., Schweder T., et al. Physiological responses to mixing in large scale bioreactors. J. Biotechnol. 2001, 85:175-185.
18. Festel G. Industrial biotechnology market size, company types, business models and growth strategies. Ind. Biotechnol. 2010, 6(2):88-94.
19. Garcia-Ochoa F., Gomez E. Bioreactor-scale-up and oxygen transfer in microbial processes: an overview. Biotechnol. Adv. 2009, 27:153-176.
20. George S., Larsson G., Enfors S.O. A scale-down two-compartment reactor with controlled substrate oscillations: metabolic response of Saccharomyces cerevisiae. Bioproc. Eng. 1993, 9:249-257.
21. Gill N.K., Appleton M., Baganz F., Lye G.J. Quantification of power consumption and oxygen transfer characteristics of a stirred miniature bioreactor for predictive fermentation scale-up. Biotechnol. Bioeng. 2008, 100(6):1144-1155.
22. Hewitt C., Nebe-von Caron G., Axelsson B., McFarlane C.M., Nienow A.W. Studies related to the scale-up of high-cell-density E coli fed-batch fermentations using multiparameter flow cytometry: effect of a changing microenvironment with respect to glucose and dissolved oxygen concentration. Biotechnol. Bioeng. 2000, 70(4):381-390.
23. Hewitt C.J., Oneyeaka H., Lewis G., Taylor I.W., Nienow A.W. A comparison of high cell density fed-batch fermentations involving both induced and non-induced recombinant Escherichia coli under well-mixed small-scale and simulated poorly mixed large-scale conditions. Biotechnol. Bioeng. 2008, 96(3):495-505.
24. Hewitt C.J., Nienow A.W. The scale-up of microbial batch and fed-batch fermentation processes. Adv. Appl. Microbiol. 2007, 62:105-135.
25. Hiller J., Franco-Lara E., Papaioannou V., Weuster-Botz D. Fast sampling and quenching procedures for microbial metabolic profiling. Biotechnol. Lett. 2007, 29(8):1161-1167.
26. Hiller J., Franco-Lara E., Weuster-Botz D. Metabolic profiling of Escherichia coli cultivations: evaluation of extraction and metabolite analysis procedure. Biotechnol. Lett. 2007, 29(8):1169-1178.
27. Junker B.H. Scale-up methodologies for Escherichia coli and yeast fermentation process. J. Biosci. Bioeng. 2004, 97(6):347-364.
28. Junne S., Klinger A., Kabisch J., Schweder T., Neubauer P. A Two-compartment bioreactor system made of commercial parts for bioprocess scale-down studies: impact of oscillations on Bacillus subtilis fed-batch cultivations. Biotechnol. J. 2011, 6(8):1009-1017.
29. Kar T., Delvigne F., Masson M., Destain J., Thonart P. Investigation of the effect of different extracellular factors on the lipase production by Yarrowia lipolityca on the basis of a scale-down approach. J. Ind. Microb. Biotechnol. 2008, 35:1053-1059.
30. Lara A.R., Galindo E., Ramirez O.T., Palomares L.A. Living with heterogeneities in bioreactors. Mol. Biotechnol. 2006, 34:355-381.
31. Lara Leal A.R., Flores L., Gosset N., Bolivar G., Ramirez F., Transcriptional O.T. Metabolic response of recombinant Escherichia coli to spatial dissolved oxygen tension gradients simulated in a scale-down system. Biotechnol. Bioeng. 2005, 93(2):372-385.
32. Lara A.R., Tyamaz-Nikerel H., Mashego M.R., van Gulik W.M., Heijnen J.J., Ramirez O.T., van Winden W.A. Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses. Biotechnol. Bioeng. 2009, 104(6):1153-1161.
33. Lange H.C., Eman M., van Zuijlen D., Visser D., van Dam J.C., Framk J., de Mattos M.J.T., Heijnen J.J. Improved rapid sampling for the in vivo kinetics of intracellular metabolites in Saccharomyces cerevisiae. Biotechnol. Bioeng. 2001, 75:406-415.
34. Langheinrich C., Nienow A.W. Control of pH in large-scale, free suspension animal cell bioreactors: alkail addition and pH excursions. Biotechnol. Bioeng. 1999, 66:171-179.
35. Lapin A., Müller D., Reuss M. Dynamic behavior of microbial populations in stirred bioreactors simulated with Euler-Lagrange methods: travelling along the lifeline of single cells. Ind. Eng. Chem. Res. 2004, 43:4647-4657.
36. Lapin A., Schmid J., Reuss M. Modeling the dynamics of E. coli populations in the three-dimensional turbulent field of a stirred-tank bioreactor-a structured-segregated approach. Chem. Eng. Sci. 2006, 61:4783-4797.
37. Liden G. Understanding the bioreactor. Bioproc. Biosyst. Eng. 2002, 24:273-279.
38. Lin H.Y., Neubauer P. Influence of glucose oscillations on a fed-batch process of recombinant Escherichia coli. J. Biotechnol. 2000, 79:27-37.
39. Magnus J.B., Hollwedel D., Oldiges M., Takors R. Monitoring and modeling of reaction dynamics in the valine/leucine synthesis pathway in Corynebacterium glutamicum. Biotechnol. Prog. 2007, 22:1071-1083.
40. Marx A., Hewitt C.J., Grewal R., Scheer S., Vandré K., Pfefferle W., Kossmann B., Ottersbach P., Beimfohr C., Snaidr J., Augé C., Reuss M. Anwendung der Zytometrie in der Biotechnologie. Chem. Ing. Tech. 2003, 60:8-614.
41. Mashego M.R., van Gulik W.M., Vinke J.L., Heijnen J.J. Critical evaluation of sampling techniques for residual glucose determination in carbon-limited chemostat culture of Saccharomyces cerevisiae. Biotechnol. Bioeng. 2003, 83:395-399.
42. Mashego M.R., van Gulik W.M., Vinke J.L., Visser D., Heijnen J.J. In vivo kinetics with rapid perturbation experiments in Saccharomyces cerevisiae using a second-generation. BioScope Metab. Eng. 2006, 8(4):370-383.
43. Mauch K., Vaseghi S., Reuss M. Quantitative analysis of metabolic and signalling pathways in Saccharomyces cerevisiae. Bioreaction Engineering 2000, 435-477. Springer Verlag, ISBN 3-540-66906. K. Schügerl, K.H. Bellgardt (Eds.).
44. Moes J., Griot M., Keller J., Heinzle E., Dunn I.J., Bourne J.R. A microbial culture with oxygen-sensitive product distribution as a potential tool for characterizing bioreactor oxygen transport. Biotechnol. Bioeng. 1984, 17:482-489.
45. Neubauer P., Häggström L., Enfors S.-O. Influence of substrate oscillations on acetate formation and growth yield in Escherichia coli glucose limited fed-batch cultivations. Biotechnol. Bioeng. 1995, 47:139-146.
46. Neubauer P., Junne S. Scale-down simulators for metabolic analysis of large-scale bioprocesses. Curr. Opin. Biotechnol. 2010, 21:114-121.
47. Noorman H. An industrial perspective on bioreactor scale-down: what can we learn from combined large-scale bioprocess and model fluid studies. Biotechnol. J. 2011, 6(8):934-943.
48. Oldiges M., Kunze M., Degenring D., Sprenger G.A., Takors R. Stimulation, monitoring and analysis of pathway dynamics by metabolic profiling in the aromatic amino acid pathway. Biotechnol. Prog. 2004, 20:1623-1633.
49. Oldiges M., Takors R. Applying metabolic profiling techniques for stimulus-response experiments: chances and pitfalls. Adv. Biochem. Eng. Biotechnol. 2005, 92:173-196.
50. Oldiges M., Lütz S., Pflug S., Schroer K., Stein N., Wiendahl C.A. Metabolomics: current state and evolving methodologies and tools. Appl. Microbiol. Biotechnol. 2007, 76:495-511.
51. Oldshue J.Y. Fermentation mixing scale-up techniques. Biotechnol. Bioeng. 1966, 3:3-24.
52. Oneyeaka H., Nienow A.W., Hewitt C.J. Further studies to the scale-up of high cell density Escherichia coli fed-batch fermentations: the additional effect of changing microenvironment when using aqueous ammonia to control pH. Biotechnol. Bioeng. 2003, 84(4):474-484.
53. Oosterhuis N.M.G., Kossen N.W.F. Dissolved oxygen concentration profiles in a production-scale bioreactor. Biotechnol. Bioeng. 1983, 16:546-550.
54. Oosterhuis, Kossen N.M.G., Olivier N.W.F., Schenk A.P.C., Scale-Down E.S. Optimization studies of the gluconic acid fermentation by Gluconobacer oxydans. Biotechnol. Bioeng. 1985, 27:711-720.
55. Paschold, H., Weuster-Botz, D., Schäfer, U., Boos, W., 1998. Verfahren zur schnellen Probennahme biologischer Proben. German Patent DE 19705289.
56. Rao D.V.K., Ramu C.T., Rao J.V., Narasu M.L., Rao A.K.S.B. Impact of dissolved oxygen concentration on some key parameters and production of rhG-CSF in batch fermentation. J. Ind. Microbiol. Biotechnol. 2008, 35:991-1000.
57. Reijenga K.A., Bakker B.M., van der Weijden C.C., Westerhoff H.V. Training of yeast cell dynamics. FEBS J. 2005, 161:6-1624.
58. Reuss M. Oxygen transfer and mixing scale-up implications. Biotechnology 1993, VCH Verlag, Weinheim. H.J. Rehm, G. Reed (Eds.).
59. Reuss M., Schmalzriedt S., Jenne M. Application of computational fluid dynamics (CFD) to modeling stirred tank bioreactors. Bioreaction Engineering 1996, Springer Verlag, Berlin, ISBN 3-540-66906-X. K. Schügerl, K.H. Bellgardt (Eds.).
60. Reuss M., Aguilera-Vazquez L., Mauch K. Reconstruction of dynamic network models from metabolite measurement. Top. Curr. Genet. 2007, 18.
61. Rizzi M., Baltes M., Theobald U., Reuss M. In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: II. Mathematical model. Biotechnol. Bioeng. 1997, 55(4):592-608.
62. Sandoval-Basurto E.A., Gosset G., Bolivar F., Ramirez O.T. Culture of Escherichia coli under dissolved oxygen gradients simulated in a two-compartment scale-down system: metabolic response and production of recombinant protein. Biotechnol. Bioeng. 2004, 89(4):453-463.
63. Schaub J., Schiesling C., Reuss M., Dauner M. Integrated sampling procedure for metabolome analysis. Biotechnol. Prog. 2006, 22(5):1434-1442.
64. Schädel F., Franco-Lara E. Rapid sampling devices for metabolic engineering applications. Appl. Microbiol. Biotechnol. 2009, 83:199-208.
65. Schäfer U., Boos W., Takors R., Weuster-Botz D. Automated sampling device for monitoring intracellular metabolite dynamics. Anal. Biochem. 1999, 270:88-96.
66. Schilling, B.M., Pfefferle, W., Bachmann, B., Leuchtenberger, W., Deckwer, W.-D., 1996. German Patent DE 19520485 A1.
67. Schilling B.M., Pfefferle W., Bachmann B., Leuchtenberger W., Deckwer W.-D. A special reactor design for investigations of mixing time effects in a scaled-down industrial l-lysine fed-batch fermentation process. Biotechnol. Bioeng. 1999, 64(5):599-606.
68. Schmalzriedt S., Jenne M., Mauch K., Reuss M. Integration of physiology and fluid dynamics. Adv. Biochem. Eng. 2003, 80:19-68.
69. Schmidt F.R. Optimization and scale up of industrial fermentation processes. Appl. Microbiol. Biotechnol. 2005, 68:425-435.
70. Schweder T. Bioprocess monitoring by marker gene analysis. Biotechnol. J. 2011, 6(8):926-933.
71. Schweder T., Krüger E., Xu B., Jürgen B., Blomsten G., Enfors S.-O., Hecker M. Monitoring of genes that respond to process-related stress in large-scale bioprocesses. Biotechnol. Bioeng. 1999, 65(2):151-159.
72. Singh V., Hensler W., Fuchs R., Constantinides A. On-line determination of mixing parameters in fermentors using pH transients. Proc. Int. Conf. Bioreactor Fluid Dynamics Paper, vol. 18 1986, 231-256. BHRA, Cambridge, UK.
73. Sweere A.P.J., Mesters J.R., Janse L., Luyben K.Ch.A.M. Experimental simulation of oxygen profiles and their influence on baker's yeast production: I. One-fermentor system. Biotechnol. Bioeng. 1998, 31:567-578.
74. Sweere A.P.J., Janse L., Luyben K.Ch.A.M. Experimental simulation of oxygen profiles and their influence on baker's yeast production: II. Two-fermentor system. Biotechnol. Bioeng. 1998, 31:579-586.
75. Sweere A.P.J., Matla Y.A., Zandvliet J., Luyben K.Ch.A.M., Kossen N.W.F. Experimental simulation of glucose fluctuations. Appl. Microbiol. Biotechnol. 1988, 28:109-115.
76. Theobald U., Mailinger W., Reuss M., Rizzi M. In vivo analysis of glucose-induced fast changes in yeast adenine nucleotide pool applying a rapid sampling technique. Anal. Biochem. 1993, 214:31-37.
77. Theobald U., Mailinger W., Baltes M., Rizzi M., Reuss M. In vivo analysis of metabolic dynamics in Saccharomyces cerevisiae: I. Experimental observations. Biotechnol. Bioeng. 1997, 55(2):305-316.
78. Vardar-Sukan F. Foaming consequences, prevention and destruction. Biotechnol. Adv. 1998, 16(5/6):913-948.
79. Visser D., van Zuylen G.A., van Dam J.C., Oudshoorn A., Eman M.R., Ras C., van Gulik W.M., Frank J., van Dedem G.W.K., Heijnen J.J. Rapid sampling for analysis of in vivo kinetics using the BioScope: a system for continuous-pulse experiments. Biotechnol. Bioeng. 2002, 79:674-681.
80. Vrabel P., Van der Lans R.G.J.M., Cui Y.Q., Luyben K.Ch.A.M. Compartment model approach: mixing in large-scale aerated reactors with multiple impellers. Chem. Eng. Res. Des. 1999, 77(4):291-302.
81. Vrabel P., van der Lans R.G.J.M., van der Schot F.N., Luyben K.Ch.A.M., Xu B., Enfors S.-O. CMA: integration of fluid dynamics and microbial kinetics in modeling of large-scale fermentations. Chem. Eng. J. 2001, 84:463-474.
82. Weuster-Botz D. Sampling tube device form monitoring intracellular metabolite dynamics. Anal. Biochem. 1997, 246:225-233.
83. Weuster-Botz D., de Graf A.A. Reaction engineering methods to study intracellular metabolite concentrations. Adv. Biochem. Eng. Biotechnol. 1996, vol. 54. Springer Verlag, pp. 76-108.
84. Xu B., Jahic M., Blomsten G., Enfors S.O. Glucose overflow metabolism and mixed-acid fermentation in aerobic large-scale fed-batch processes with Escherichia coli. Appl. Microbiol. Biotechnol. 1999, 51:564-571.