ANALYSIS OF BIFURCATIONS IN CONTINUOUS FERMENTATION USING RECOMBINANTMICROORGANISMS WITH DELAYED-RESPONSES

When the feed rate to a fermenter is varied periodically in order to f avor the growth of plasmid-containing cells, a transition may occur fr om the starting stationary state to another state. The resulting state may be constant or oscillatory. A generalised model based on the adap tion times of plasmid-free and plasmid-harboring cells has been used. Analytical conditions have been derived for bifurcation from one nonos cillatory state to another or to an oscillatory state (Hopf bifurcatio n). The frequency of oscillation is shown to have an upper bound, whic h can be controlled by manipulating certain process parameters. The pr oduction of tryptophan synthetase by the plasmid pPLc23trpA1 in E. col i is used as an example to determine the nature of the Hopf bifurcatio ns.