Skip to main content
Log in

Model aided design of repeated fed-batch penicillin fermentation

  • Originals
  • Published:
Bioprocess Engineering Aims and scope Submit manuscript

Abstract

Structured models of antibiotic fermentation that quantify maturation and aging of product forming biomass are fitted to experimental data. Conditions of superiority of repeated fed batch cultivation are characterized on the basis of a performance criterion that includes penicillin productivity and costs of operation. Emphasis is placed on the relevance of such research to the model aided design of optimal cyclic operation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

c IU/mg:

cost factor

D s−1 :

dilution rate

J IU · cm−3 · h−1 :

net productivity

k p IU · mg−11 · h−1 :

specific product formation rate

k pm IU · mg−1 · h−1 :

maximum specific product formation rate

p IU/cm3 :

concentration of penicillin

T s:

final time of fermentation

t s:

fermentation time

X kg/m3 :

concentration of biomass dry weight

X 1kg/m3 :

concentration of young, immature biomass

X 2 kg/m3 :

concentration of mature product forming biomass

X c kg/m3 :

biomass concentration of the end of growth phase

X mkg/m3 :

maximum biomass concentration

α s−1 :

specific maturation rate

β s−1 :

specific aging rate

μ s−1 :

specific growth rate

μ m s−1 :

maximum specific growth rate

μ p s−1 :

specific growth rate during the product formation phase

τ s:

cycle time

γ %:

volume fraction of draw-off

CC:

chemostat culture

RFBC:

repeated fed batch culture

RBC:

repeated batch culture

References

  1. Bailey, J. E.: Periodic operation of chemical reactors: A review. Chem. Eng. Commun, 1 (1973) 111–124

    Google Scholar 

  2. Renken, A.: Instationäre Prozeßführung kontinuierlicher Reaktoren. Chem. Ing. Tech. 54 (1982) 571–580

    Google Scholar 

  3. Parulekar, S. J.; Lim, H. C.: Modeling, optimization and control of semi-batch bioreactors. Adv. Biochem. Eng. 32 (1985) 207–258

    Google Scholar 

  4. Pirt, S. J.: The theory of fed batch culture with reference to the penicillin fermentation. J. Appl. Chem. Biotechnol. 24 (1974) 415–424

    Google Scholar 

  5. Guthke, R.; Gira, G.; Mund, K.; Knorre, W. A.: Computer controlled transient state in a fed batch culture. Biotechnol. Letters 2 (1980) 315–320

    Google Scholar 

  6. Boanjak, M.; Topolovec, V.; Johanides, V.: Growth kinetics and antibiotic synthesis during the repeated fed-batch culture of Streptomycetes. Biotechnol. Bioeng. Symp. 9 (1970) 155–165

    Google Scholar 

  7. Bošnjak, M.; Stroj, A.; Curcić, M.; Adamović, V.; Gluncić, Z.; Bravar, D.: Application of scale-down experiments in the study of kinetics of oxytetracycline biosynthesis. Biotechnol. Bioeng. 27 (1985) 398–408

    Google Scholar 

  8. Dunn, I. J.; Shioya, S.; Keller, R.: Analysis of cyclic fed batch processes. In: Sikyta, B.; Fencl, Z.; Polácek, V. (Eds.): Contin. Cultiv. Microorganisms, Proc. 7th Symp. Prague 1978, pp. 189–194. Prague: Institute of Microbiology, Czechoslovak Academy of Sciences 1980

    Google Scholar 

  9. Guthke, R.; Knorre, W. A.: Efficiency of the cyclic batch antibiotic fermentation. Biotechnol. Bioeng. 24 (1982) 2129–2136

    Google Scholar 

  10. Wittler, R.; Schügerl, K.: Interrelation between penicillin productivity and growth rate. Appl. Microbiol. Biotechnol. 21 (1985) 348–355

    Article  Google Scholar 

  11. Hasegawa, W.; Shimizu, K.; Kobayashi, T.;Matsubara, M.: Efficiency of repeated batch penicillin fermentation using two fermentors. Computer Simulation and Optimisation. J. Chem. Techn. Biotechnol. 35B (1985) 33–42

    Google Scholar 

  12. Constantinides, A.; Spencer, J. L.; Gaden, Jr., E. L.: Optimization of batch fermentation processes. I. Development of mathematical models for batch penicillin fermentations. Biotechnol. Bioeng. 12 (1970) 803–830

    PubMed  Google Scholar 

  13. Guthke, R.; Knorre, W. A.: Optimal substrate profile for antibiotic fermentation. Biotechnol. Bioeng. 23 (1981) 2771–2777

    Google Scholar 

  14. Calam, C. T.; Ismail, B. A.-K.: Investigation of factors in the optimisation of penicillin production. J. Chem. Tech. Biotechnol. 30 (1980) 249–262

    Google Scholar 

  15. Shu, P.: Mathematical models for the product accumulation in microbiological processes. J. Biochem. Microbiol. Technol. Eng. 3 (1961) 95–109

    Google Scholar 

  16. Fishman, V. M.; Biryukov, V. V.: Kinetic model of secondary metabolite production and its use in computation of optimal conditions. Biotechnol. Bioeng. Symp. 4 (1974) 647–662

    Google Scholar 

  17. Nestaas, E.; Wang, D. I. C.: Computer control of the penicillin fermentation using the filtration probe in conjunction with a structured process model. Biotechnol. Bioeng. 25 (1983) 781–796

    Google Scholar 

  18. Swartz, R. W.: The use of economic analysis of penicillin G manufacturing costs in establishing priorities for fermentation process improvement. Annu. Rep. Fermentation Proc. 3 (1979) 75–110

    Google Scholar 

  19. Weigang, W. A.: Maximum cell productivity by repeated fedbatch culture for constant yield case. Biotechnol. Bioeng. 23 (1981) 249–266

    Google Scholar 

  20. Matsubara, M.; Hasegawa, S.; Shimizu, K.: Noninferior periodic operation of the biological reactor. Biotechnol. Bioeng. 27 (1985) 1214–1222

    Google Scholar 

  21. Ryu, D. D. Y.; Hospodka, J.: Quantitative physiology of Penicillium chrysogenum in penicillin fermentation. Biotechnol. Bioeng. 22 (1980) 289–298

    Google Scholar 

  22. Heijnen, J. J.; Roels, J. A.; Stouthamer, A. H.: Application of balancing methods in modeling the penicillin fermentation. Biotechnol. Bioeng. 21 (1979) 2175–2201

    PubMed  Google Scholar 

  23. Bajpai, R. K.; Reuß, M.: Evaluation of feeding strategies in carbon-regulated secondary metabolite production through mathematical modelling. Biotechnol. Bioeng. 23 (1981) 717–738

    Google Scholar 

  24. Hegewald, E.; Wolleschensky, E.; Guthke, R.; Neubert, M.; Knorre, W. A.: Instabilities of product formation in a fedbatch culture of penicillium chrysogenum. Biotechnol. Bioeng. 23 (1981) 1563–1572

    Google Scholar 

  25. Foster, J. W.; McDaniel, L. E. (1952): US-Patent 2584009

  26. Pilát, P.: The effect of sucrose feeding on semi-continuous penicillin biosynthesis. In: Sikyta, B.; Fencl, Z.; Połacek, V. (Eds.): Contin. Cultiv. Microorganisms, Proc. 7th Symp. Prague 1978, pp. 753–758. Institute of Microbiology, Czechoslovak Academy of Sciences, Prague 1980

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guthke, R., Knorre, W.A. Model aided design of repeated fed-batch penicillin fermentation. Bioprocess Engineering 2, 169–173 (1987). https://doi.org/10.1007/BF00387324

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00387324

Keywords

Navigation