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4 - Phenomena That Favor Fed-Batch Operations

Published online by Cambridge University Press:  05 April 2013

Henry C. Lim  and
Hwa Sung Shin
Henry C. Lim
Affiliation:
University of California, Irvine
Hwa Sung Shin
Affiliation:
Inha University, Seoul
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Summary

One of the primary objectives of reaction engineering is to optimize the rate of formation of the product (productivity) and/or the relative rates (selectivity or yield). For an existing plant, a faster product formation rate implies a higher productivity and corresponding reductions in plant operating time and operating cost. For a new plant to be built, the increased rate implies, in addition to improved productivity, a smaller reactor and therefore a lower capital investment cost. Likewise, an improved yield implies a lower raw material cost and a lower capital investment for existing and new plants.

Fed-batch operations are well suited for situations in which the cell growth and/or product formation rates are sensitive to the concentration of the limiting substrate, an intermediate, or a product so that the overall rate increases with the limiting substrate concentration, reaches a maximum, and decreases with further increases in the substrate concentration. Fed-batch operation finds wide applications in bioindustry as it takes advantages of various biochemical and physiological phenomena of cell cultures and is also able to overcome adverse physical effects. Fed-batch operations provide potential advantages for autocatalytic reactions, to which cellular processes belong, and multiple reactions in which the relative rates vary with the reactant concentration.

Type
Chapter
Information
Fed-Batch Cultures
Principles and Applications of Semi-Batch Bioreactors
 , pp. 52 - 61
Publisher: Cambridge University Press
Print publication year: 2013

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References

Edwards, V. H., Cottschalk, M. J., Noojin, A. Y., Tuthill, L. B., and Tannahill, A. L. 1970. Extended culture: The growth of Candida utilis at controlled acetate concentrations. Biotechnology and Bioengineering 12: 975–999.CrossRefGoogle ScholarPubMed
Yamane, T., Kishimoto, M., and Yoshida, F. 1976. Semi-batch culture of methanol assimilating bacteria with exponentially increased methanol feed. Journal of Fermentation Technology 54: 229–240.Google Scholar
Shimizu, S., Tanaka, A., and Fukui, S. 1969. Utilization of hydrocarbons by microorganisms. VII. Production of coenzyme Q by Candida tropicalis pK 233 in hydrocarbon fermentation. Effect of aromatic compounds on coenzyme Q production. Journal of Fermentation Technology 47: 551–557.Google Scholar
Renard, J. M., Mansouri, A., and Cooney, C. L. 1984. Computer controlled fed-batch fermentation of the methylotroph Pseudomonas AM1. Biotechnology Letters 6: 577–580.CrossRefGoogle Scholar
Silman, R. W. 1984. Ethanol production by Zymomonas mobilis in fed-batch fermentations. Biotechnology and Bioengineering 26: 247–251.CrossRefGoogle ScholarPubMed
Kishimoto, M., Yoshida, T., and Taguchi, H. 1980. Optimization of fed-batch culture by dynamic programming and regression analysis. Biotechnology Letters 2: 403–408.CrossRefGoogle Scholar
Kishimoto, M., Yoshida, T., and Taguchi, H. 1981. Simulation of fed-batch culture for glutamic acid production with ethanol feeding by use of regression analysis. Journal of Fermentation Technology 59: 43–48.Google Scholar
Kishimoto, M., Yoshida, T., and Taguchi, H. 1981. On-line optimal control of fed-batch culture of glutamic acid production. Journal of Fermentation Technology 59: 125–129.Google Scholar
Lee, S., and Wang, H. Y. 1982. Repeated fed-batch rapid fermentation using yeast cells and activated carbon extraction systems. Biotechnology Bioengineering Symposium 12: 221–231.Google Scholar
Dibiasio, D. 1980. An investigation of stability and multiplicity of steady states in a laboratory biological reactor. PhD dissertation, Purdue University.
Weigand, W. A., Lim, H. C., Creagan, C. C., and Mohler, R. D. 1979. Optimization of a repeated fed-batch reactor for maximum cell productivity. Biotechnology and Bioengineering Symposium 9: 335–348.Google Scholar
White, J. 1954. Yeast Technology. Vol. 31. John Wiley.Google Scholar
Crabtree, H. G. 1929. Observations on the carbohydrate metabolism of tumors. Biochemistry Journal 23: 536–545.CrossRefGoogle Scholar
Whitaker, A. 1980. Fed-batch culture. Process Biochemistry 15: 10–12, 14–15, 32.Google Scholar
Moss, F. J., Rickard, P. A. D., Bush, F. E., and Caiger, P. 1971. The response by microorganisms to steady-state growth in controlled concentrations of oxygen and glucose. II. Saccharomyces carlsbergensis. Biotechnology and Bioengineering 13: 63–75.CrossRefGoogle Scholar
Nanba, A., Hirota, F., and Nagai, S. 1981. Microcomputer-coupled baker's yeast production. Journal of Fermentation Technology 59: 383–389.Google Scholar
Hosler, P., and Johnson, M. J. 1953. Penicillin from chemically defined media. Industrial and Engineering Chemistry 45: 871–874.CrossRefGoogle Scholar
Clark, D. J., and Marr, A. G. 1964. Studies on the repression of β-galactosidase in Escherichia coli. Biochemistry Biophysics Acta 92: 85–94.Google ScholarPubMed
Hsu, E. J., and Vaughn, R. H. 1969. Production and catabolite repression of the constitutive polygalacturonic acid trans-eliminase of Aeromonas liquefaciens. Journal of Bacteriology 98: 172–181.Google ScholarPubMed
Yamane, K., Suzuki, H., and Nishizawa, K. 1970. Purification and properties of extracellular and cell-bound cellulase components of Pseudomonas fluorescens var. cellulosa. Journal of Biochemistry 67: 19–35.CrossRefGoogle ScholarPubMed
Hulme, M. A., and Strank, D. W. 1970. Induction and the regulation of production of cellulose by fungi. Nature 226: 469–470.CrossRefGoogle Scholar
Hockenhull, D. J. D., and Mackenzie, R. M. 1968. Present nutrient feeds for penicillin fermentation on defined mediums. Chemistry and Industry 19: 607–610.Google Scholar
Gray, P. P., Dunnill, P., and Lilly, M. D. 1973. The effect of controlled feeding of glycerol on β-galactosidase production by Escherichia coli in batch culture. Biotechnology and Bioengineering 15: 1179–1188.CrossRefGoogle ScholarPubMed
Allen, A., and Andreotti, R. E. 1982. Cellulase production in continuous and fed-batch culture by Trichoderma reesei MCG 80. Biotechnology and Bioengineering Symposium 12: 451–459.Google Scholar
Gottvaldova, M., Kucera, J., and Podrazky, V. 1982. Enhancement of cellulase production by Trichoderma viride using carbon/nitrogen double-fed-batch. Biotechnology Letters 4: 229–231.CrossRefGoogle Scholar
Gottvaldova, M., Kucera, J., and Podrazky, V. 1982. Fed-batch cultivation of Trichoderma viride: Effect of pH and nitrogen source supplementation on cellulase production. Biotechnology Letters 4: 645–646.CrossRefGoogle Scholar
Hendy, N., Wilke, C., and Blanch, H. 1982. Enhanced cellulase production using Solka floc in a fed-batch fermentation. Biotechnology Letters 4: 785–788.CrossRefGoogle Scholar
Hendy, N., Wilke, C., and Blanch, H. 1984. Enhanced cellulase production in fed-batch culture of Trichoderma reesei C-30. Enzyme and Microbial Technology 6: 73–77.CrossRefGoogle Scholar
McLean, D., and Podruzny, M. F. 1985. Further support for fed-batch production of cellulases. Biotechnology Letters 7: 683–688.CrossRefGoogle Scholar
Matsumura, M., Imanaka, T., Yoshida, T., and Taguchi, H. 1981. Modeling of cephalosporin C production and its application to fed-batch culture. Journal of Fermentation Technology 59: 115–123.Google Scholar
Rutkov, A. B. 1984. Microbiological production of L-lysine by employing fed batch cultivation. Doklady Bolgarskoi Akademii Nauk 37: 1677–1680.Google Scholar
Vu-Trong, K., and Gray, P. P. 1984. Stimulation of enzymes involved in tylosin biosynthesis by cyclic feeding profiles in fed batch cultures. Biotechnology Letters 6: 435–440.CrossRefGoogle Scholar
Vu-Trong, K., and Gray, P. P., eds. 1982. Proceedings of the 5th Australian Biotechnology Conference, University of New South Wales.Google Scholar
Vu-Trong, K., and Gray, P. P. 1982. Stimulation of tylosin productivity resulting from cyclic feeding profiles in fed batch cultures. Biotechnology Letters 4: 725–728.CrossRefGoogle Scholar
Matsumura, M., Imanaka, T., Yoshiuda, T., and Taguchi, H. 1978. Effect of glucose and methionine consumption rates on cephalosporin C production by Cephalosporium acremonium. Journal of Fermentation Technology 56: 345–353.Google Scholar
Matsumura, M., Imanaka, T., Yoshiuda, Y., and Taguchi, H. 1981. Optimal conditions for production of cephalosporin C in fed-batch culture. Advances in Biotechnology 1: 297–302.Google Scholar
Galliher, P. M., Cooney, C. L., Langer, R., and Lindhart, R. J. 1981. Heparinase production by Flavobacterium heparinum. Applied Environmental Microbiology 41: 360–365.Google ScholarPubMed
Yamane, T., and Tsukano, M. 1977. Kinetic studies on fed-batch cultures. V. Effect of several substrate-feeding modes on production of extracellular α-amylase by fed-batch culture of Bacillus megaterium. Journal of Fermentation Technology 55: 233–242.Google Scholar
Shin, S. B., Kitagawa, Y., Suga, K., and Ichikawa, K. 1978. Cellulase biosynthesis by Trichoderma viride on soluble substrates. Journal of Fermentation Technology 56: 396–402.Google Scholar
Waki, T., Suga, K., and Ichigawa, K. 1981. Production of cellulase in fed-batch culture. Advances in Biotechnology 1: 359–364.Google Scholar
Ohno, H., Nakanishi, E., and Takamatsu, T. 1976. Optimal control of a semi-batch fermentation. Biotechnology and Bioengineering 18: 847–864.CrossRefGoogle Scholar
Suzuki, T., Mori, H., Yamane, T., and Shimizu, S. 1985. Automatic supplementation of minerals in fed-batch culture to high cell mass concentration. Biotechnology and Bioengineering 27: 192–201.CrossRefGoogle ScholarPubMed
Demain, A. L. 1971. Overproduction of microbial metabolites and enzymes due to alteration of regulation. Advances in Biochemical Engineering 1: 113–142.CrossRefGoogle Scholar
Bailey, E. J., and Ollis, D. F. 1986. Biochemical Engineering Fundamentals. 2nd ed. McGraw-Hill.Google Scholar
Bauer, S., and Schiloach, J. 1974. Maximal exponential growth rate and yield of E. coli obtainable in a bench-scale fermentor. Biotechnology and Bioengineering 16: 933–941.CrossRefGoogle Scholar
Mori, H., Yano, T., Kobayashi, T., and Shimizu, S. 1979. High density cultivation of biomass in fed-batch system with DO-Stat. Journal of Chemical Engineering, Japan 12: 313–319.CrossRefGoogle Scholar
Riesenberg, D., and Guthke, R. 1999. High-cell-density cultivation of microorganisms. Applied Microbiology and Biotechnology 51: 422–430.CrossRefGoogle ScholarPubMed
Kobayashi, T., Yano, T., Mori, H., and Shimizu, S. 1979. Cultivation of microorganisms with a DO-stat and a silicone tubing sensor. Biotechnology and Bioengineering Symposium 9: 73–83.Google Scholar
Mori, H., Kobayashi, T., and Shimizu, S. 1981. High density production of sorbose from sorbitol by fed-batch culture with DO-stat. Journal of Chemical Engineering, Japan 14: 65–70.CrossRefGoogle Scholar
Nishio, N., Tsuchiya, Y., Hayashi, M., and Nagai, S. 1979. Studies on methanol metabolism. VI. A fed-batch culture of methanol-utilizing bacteria with pH stat. Journal of Fermentation Technology 55: 151–155.Google Scholar
Yamauchi, H., Mori, H., Kobayashi, T., and Shimizu, S. 1983. Mass production of lipids by Lipomyces starkeyi in microcomputer-aided fed-batch culture. Journal of Fermentation Technology 61: 275–280.Google Scholar
Park, C. B., and Lee, S. B. 1997. Constant-volume fed-batch operation for high density cultivation of hyperthermophilic aerobes. Biotechnology Techniques 11: 277–281.CrossRefGoogle Scholar
Huang, W.-B., and Chu, S. Y. 1984. Ethanol production by Zymomonas mobilis in fed-batch fermentations. Biotechnology and Bioengineering 26: 247–251.Google Scholar
Lim, H. C., Tayeb, Y. J., Modak, J. M., and Bonte, P. 1986. Computational algorithms for optimal feed rates for a class of fed-batch fermentation: Numerical results for penicillin and cell mass production. Biotechnology and Bioengineering 28: 1408–1420.CrossRefGoogle ScholarPubMed
Vicik, S. M., Fedor, A. J., and Swartz, R. W. 1990. Defining an optimal carbon source/methionine feed strategy for growth and cephalosporin C formation by Cephalosporium acremonium. Biotechnology Progress 6: 333–340.CrossRefGoogle ScholarPubMed
Bajpai, R. K., and Reub, M. 1981. Evaluation of feeding strategies in carbon-regulated secondary metabolite production through mathematical modeling. Biotechnology and Bioengineering 23: 717–738.CrossRefGoogle Scholar
Bhargava, S., Nandakumar, M. P., Roy, A., Wenger, K. S., and Marten, M. R. 2003. Pulsed feeding during fed-batch fungal fermentation leads to reduced viscosity without detrimentally affecting protein expression. Biotechnology and Bioengineering 81: 341–347.CrossRefGoogle ScholarPubMed
De Swaaf, M. E., Sijtsma, L., and Pronk, J. T. 2003. High-cell-density fed-batch cultivation of the docosahexaenoic acid producing marine alga Crypthecodinium cohnii. Biotechnology and Bioengineering 81: 666–672.CrossRefGoogle ScholarPubMed
Jeffries, T. W., Fady, J. H., and Lightfoot, E. N. 1985. Effect of glucose supplements on the fermentation of xylose by Pachysolen tannophilus. Biotechnology and Bioengineering 27: 171–176.CrossRefGoogle ScholarPubMed
Koshimizu, L. H., Valdeolivas Gomez, E. I., Bueno Netto, C. L., Regina de Melo Cruz, M., Vairo, M. L. R., and Borzani, W. 1984. Constant fed-batch ethanol fermentation of molasses. Journal of Fermentation Technology 62: 205–210.Google Scholar
Park, C. B., and Lee, S. B. 1997. Constant-volume fed-batch operation for high density cultivation of hyperthermophilic aerobes. Biotechnology Techniques 11: 277–281.CrossRefGoogle Scholar
Lo Curto, R. B., and Tripodo, M. M. 2001. Yeast production from virgin grape marc. Bioresource Technology 78: 5–9.CrossRefGoogle ScholarPubMed
Rangel-Yagui, C. de O., Danesi, E. D., de Carvalho, J. C., and Sato, S. 2004. Chlorophyll production from Spirulina platensis: Cultivation with urea addition by fed-batch process. Bioresource Technology 92: 133–141.CrossRefGoogle Scholar
Lee, H. H., and Yau, B. O. 1981. An experimental reactor for kinetic studies: Continuously fed batch reactor. Chemical Engineering Science 36: 483–488.CrossRefGoogle Scholar
Hardjito, L., Greenfield, P. F., and Lee, P. L. 1993. Recombinant protein production via fed-batch culture of the yeast Saccharomyces cerevisiae. Enzyme and Microbial Technology 15: 120–126.CrossRefGoogle ScholarPubMed
Keller, R., and Dunn, I. J. 1978. Fed-batch microbial culture: Models, errors and applications. Journal of Applied Chemistry and Biotechnology 28: 508–514.Google Scholar
Esener, A. A., Roels, J. A., and Kossen, N. W. F. 1981. Fed-batch culture: Modeling and application in the study of microbial energetics. Biotechnology and Bioengineering 23: 1851–1871.CrossRefGoogle Scholar
Ramirez, O. T., Zamora, R., Quintero, R., and Lopez-Munguia, A. 1994. Exponentially fed-batch cultures as an alternative to chemostats: The case of penicillin acylase production by recombinant E. coli. Enzyme and Microbial Technology 16: 895–903.CrossRefGoogle ScholarPubMed
Sterkenburg, A., Prozee, G. A. P., Leegwater, P. A. J., and Wouters, J. T. M. 1984. Expression and loss of the pBR322 plasmid in Klebsiella aerogenes NCTC 418, grown in chemostat culture. Antonie van Leeuwenhoek 50: 397–404.CrossRefGoogle ScholarPubMed
Chew, L. C. K., Tacon, W. C. A., and Cole, J. A. 1988. Effect of growth conditions on the rate of loss of the plasmid pAT153 from continuous cultures of Escherichia coli HB101. FEMS Microbiology Letters 56: 101–104.CrossRefGoogle Scholar
Tottrup, H. V., and Carlsen, S. 1990. A process for the production of human proinsulin in Saccharomyces cerevisiae. Biotechnology and Bioengineering 35: 339–348.CrossRefGoogle ScholarPubMed
Siegel, R., and Ryu, D. D. Y. 1985. Kinetic study of instability of recombinant plasmid pPLc23 trpA1 in E. coli using two-stage continuous culture system. Biotechnology and Bioengineering 27: 28–33.CrossRefGoogle Scholar
Nancib, N., and Boudrant, J. 1992. Effect of growth rate on stability and gene expression of a recombinant plasmid during continuous cultures of Escherichia coli in non-selective medium. Biotechnology Letters 14: 643–648.CrossRefGoogle Scholar
Enberg, B., and Nordstrom, K. 1975. Replication of R-factor R1 in Escherichia coli K-12 at different growth rates. Journal of Bacteriology 123: 179–186.Google Scholar
Curless, C., Pope, J., and Tsai, L. 1990. Effect of pre-induction specific growth rate on recombinant alpha consensus interferon synthesis in Escherichia coli. Biotechnology Progress 6: 149–152.CrossRefGoogle Scholar
Bentley, W. E., Mirjalili, N., Andersen, D. C., Davis, R. H., and Kompala, D. S. 1990. Plasmid-encoded protein: The principal factor in the “metabolic burden” associated with recombinant bacteria. Biotechnology and Bioengineering 35: 668–681.CrossRefGoogle ScholarPubMed
Seo, J.-H., and Bailey, J. E. 1985. Effects of recombinant plasmid content on growth properties and cloned gene product formation in Escherichia coli. Biotechnology and Bioengineering 27: 1668–1674.CrossRefGoogle ScholarPubMed
Riesenberg, D., Menzel, K., Schulz, V., Schumann, K., Veith, G., Zuber, G., and Knorre, W. A. 1990. High cell density fermentation of recombinant Escherichia coli expressing chuman interferon alpha 1. Applied Microbiology and Biotechnology 34: 77–82.CrossRefGoogle Scholar
Ryan, W., and Parulekar, S. J. 1991. Recombinant protein synthesis and plasmid instability in continuous cultures of Escherichia coli JM103 harboring a high copy number plasmid. Biotechnology and Bioengineering 37: 415–429.CrossRefGoogle ScholarPubMed
Seo, J.-H., and Bailey, J. E. 1986. Continuous cultivation of recombinant Escherichia coli: Existence of an optimum dilution rate for maximum plasmid and gene product concentration. Biotechnology and Bioengineering 28: 1590–1594.CrossRefGoogle ScholarPubMed
Park, S., Ryu, D. D. Y., and Kim, J. Y. 1990. Effect of cell growth rate on the performance of a two-stage continuous culture system in a recombinant Escherichia coli fermentation. Biotechnology and Bioengineering 36: 493–505.CrossRefGoogle Scholar
Ramirez, O. T., Zamora, R., Espinosa, G., Merino, E., Bolivar, F., Quintero, R. 1994. Kinetic study of penicillin acylase production by recombinant E. coli in batch cultures. Process Biochemistry 29: 197–206.CrossRefGoogle Scholar
Curless, F. K., Swank, R., Menjares, A., Fieschko, J., and Tsai, L. 1991. Design and evaluation of a two-stage, cyclic, recombinant fermentation process. Biotechnology and Bioengineering 38: 1082–1090.CrossRefGoogle ScholarPubMed
Jensen, E. B., and Carlsen, S. 1990. Production of recombinant human growth hormone in Escherichia coli: Expression of different precursors and physiological effects of glucose, acetate, and salts. Biotechnology and Bioengineering 36: 1–11.CrossRefGoogle ScholarPubMed
Zabriskie, D. W., Wareheim, D. A., and Plansky, M. J. 1987. Effects of fermentation feeding strategies prior to induction of expression of a recombinant malaria antigen in Escherichia coli. Journal of Industrial Microbiology 2: 87–95.CrossRefGoogle Scholar
Nasri, M., Sayadi, S., Barbotin, J. N., and Thomas, , , D. 1987. The use of the immobilization of whole living cells to increase stability of recombinant plasmids in Escherichia coli. Journal of Biotechnology 6: 147–157.CrossRefGoogle Scholar
Horn, U., Krug, M., and Sawistoski, J. 1990. Effect of high density cultivation on plasmid copy number in recombinant Escherichia coli cells. Biotechnology Letters 12: 191–196.CrossRefGoogle Scholar
Kojima, I., Yoshikawa, H., Okazaki, M., and Terui, Z. 1972. Studies on riboflavin production by Eremothecium ashbyii. Journal of Fermentation Technology 50: 716–723.Google Scholar
Dalton, C. C. 1983. Chlorophyll production in fed-batch cultures of Ocimum basilicum (sweet basil). Plant Science Letters 32: 263–270.CrossRefGoogle Scholar
Woods, M., and Millis, N. F. 1985. Effect of slow feeding of xylose on ethanol yield by Pachysolen tannophilus. Biotechnology Letters 7: 679–682.CrossRefGoogle Scholar
Glick, R. G., and Pasternak, J. J. 1998. Molecular Biotechnology: Principles and Applications of Recombinant DNA. ASM Press.Google Scholar

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