Canadian Journal of Chemical Engineering, Vol.72, No.5, 929-934, 1994
Effect of Feed Cycling on Plasmid Stabilization During Continuous Fermentation - The Case of Variable Plasmid Loss Probability
The effect of feed cycling on the stability of plasmid-bearing cells during continuous fermentation has been analysed for the case where the probability of loss of the plasmid varies with time. The model consists of a system of delayed differential equations. By using a square-wave profile of the dilution rate, a two-fold increase in the concentration of plasmid-bearing cells and the recombinant product can be achieved over what is possible with a constant dilution rate. The dilution rate has a stronger effect than the frequency. These results agree qualitatively with reported experiments. The plasmid loss probability and the differential growth rate show fluctuations for a square-wave variation in the dilution rate, and even with a constant dilution rate they stabilise only after a length of time. These observations show that it is particularly important to account for variable plasmid loss probability in the initial phase of fermentation.
Keywords:CONTINUOUS CULTURE;SACCHAROMYCES-CEREVISIAE;ESCHERICHIA-COLI;BEARING CELLS;DILUTION RATE;STABILITY;MAINTENANCE;EXPRESSION;CSTR;MICROORGANISMS