Analysis of bifurcations in continuous fermentation using recombinant microorganisms with delayed responses
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Abstract
When the feed rate to a fermenter is varied periodically in order to favor the growth of plasmid-containing cells, a transition may occur from the starting stationary state to another state. The resulting state may be constant or oscillatory. A generalised model based on the adaption times of plasmid-free and plasmid-harboring cells has been used. Analytical conditions have been derived for bifurcation from one nonoscillatory state to another or to an oscillatory state (Hopf bifurcation). The frequency of oscillation is shown to have an upper bound, which can be controlled by manipulating certain process parameters. The production of tryptophan synthetase by the plasmid pPLc23trpAl in E. coli is used as an example to determine the nature of the Hopf bifurcations.
Keywords
Waste Water Fermentation Water Management Water Pollution TryptophanList of Symbols
- D l/h
dilution rate
- Km g/l
Monod constant
- p
probability of plasmid loss per generation
- s g/l
substrate concentration
- t h
time
- Ti h
delay time of cells ofi-th kind
- Xi g/l
concentration of cells ofi-th kind
- Yi g/g
yield coefficient of cells ofi-th kind
Greek Symbols
- μi l/h
specific growth rate of i-th species
- μim l/h
maximum possible value ofμ i
- τ h
generalised delay time
Subscripts
- 1
cells without plasmids
- 2
cells with plasmids
- s
steady state
Superscript
- o
inlet stream
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References
- 1.Baylor, D. A.;Hodgkin, A. L.;Lamb, T. D.: The electrical response of turtle cones to flashes and steps of light. J. Physiol. 242 (1974) 685–727CrossRefGoogle Scholar
- 2.MacDonald, N.: Cyclical neutropenia: models with two cell types and two time lags. In: Valleron, A. J.; MacDonald, P. D. M. (Eds.) Biomathematics and Cell Kinetics, pp. 287–295. Amsterdam: North Holland 1978Google Scholar
- 3.Plant, R. E.: A Fitzhugh differential-difference equation modeling recurrent neural feedback. SIAM J. Appl. Math. 40 (1981) 150–162CrossRefGoogle Scholar
- 4.MacDonald, N.: Time delays in chemostat models. In: Brazin, M. J. (Ed.) Microbial Population Dynamics, pp. 33–53. Boca Raton, Florida: C. R. C. Press 1982Google Scholar
- 5.Lyberatos, G.: The effect of delay on the feedback identification of chemical reaction systems. Chem. Eng. Sci. 40 (1985) 2160–2162CrossRefGoogle Scholar
- 6.Powell, E. O.: Hypertrophic growth. J. Appl. Chem. Biotechnol. 22 (1972) 71–78CrossRefGoogle Scholar
- 7.O'Neill, D. G.;Lyberatos, G.: Feedback identification of continuous microbial growth systems. Biotechnol. Bioeng. 28 (1986) 1323–1333CrossRefGoogle Scholar
- 8.Stephens, M. L.;Christensen, C.;Lyberatos, G.: Plasmid stabilization of an Escherichia coli culture through cycling. Biotechnol. Prog. 8 (1992) 1–4CrossRefGoogle Scholar
- 9.Summers, D. K.: The kinetics of plasmid loss. Trends Biotechnol. 9 (1991) 273–278CrossRefGoogle Scholar
- 10.Stephens, M. L.;Lyberatos, G.: Effect of cycling on final mixed culture fate. Biotechnol. Bioeng. 29 (1987) 672–678CrossRefGoogle Scholar
- 11.Stephens, M. L.;Lyberatos, G.: Effect of cycling on the stability of plasmid-bearing microorganisms in continuous culture. Biotechnol. Bioeng. 31 (1988) 464–469CrossRefGoogle Scholar
- 12.Weber, A. E.;San, K.-Y.: Enhanced plasmid maintenance in a CSTR upon square-wave oscillations in the dilution rate. Biotechnol. Lett. 10 (1988) 531–536CrossRefGoogle Scholar
- 13.Ollis, D. F.;Chang, H. T.: Batch fermentation kinetics with unstable recombinant cultures. Biotechnol. Bioeng. 24 (1982) 2583–2586CrossRefGoogle Scholar
- 14.Lee, S. B.;Ryu, D. D. Y.;Seigel, R.;Park, S. H.: Performance of recombinant fermentation and evaluation of gene expression efficiency for gene product in two-stage continuous culture system. Biotechnol. Bioeng. 31 (1988) 805–820CrossRefGoogle Scholar
- 15.Lee, S. B.;Seressiotsis, A.;Bailey, J. E.: A kinetic model for product formation in unstable recombinant populations. Biotechnol. Bioeng. 27 (1985) 1699–1709CrossRefGoogle Scholar
- 16.Ioos, G.;Joseph, D. D.: Elementary Stability and Bifurcation Theory, Heidelberg: Springer Verlag 1980CrossRefGoogle Scholar
- 17.Lyberatos, G.;Kuszta, B.;Bailey, J. E.: Normal forms for chemical reaction systems via the affine transformation. Chem. Eng. Sci. 40 (1985) 1177–1189CrossRefGoogle Scholar
- 18.MacDonald, N.: Biological Delay Systems: Linear Stability Theory, Ch. 6. Cambridge: Cambridge University Press 1989Google Scholar
- 19.Patnaik, P. R.: Dependence of process variables on fermentation parameters during start-up of a continuous flow reactor with recombinant microorganisms. Biotechnol. Lett. 7 (1993) 137–142Google Scholar