OPTIMAL-CONTROL OF FED-BATCH FERMENTATION WITH AUTOINDUCTION OF METABOLITE PRODUCTION

Induction of metabolite production is a common feature of many culture s obtained by recombinant DNA technology. Synthesis of a product in th ese cultures is triggered by a sharp change in environmental condition s or by autoinduction in which the cells, under conditions of growth l imitation, produce a species that initiates the synthesis. If product synthesis is the objective of the fermentation, then the time of induc tion should be optimized so that enough biomass is produced prior to i nduction while ample nutrient is left in the broth to sustain product synthesis after induction. In this study, recombinant luminous Escheri chia coli has been used to portray an autoinductive culture in batch a nd fed-batch fermentations. A model describing the cell density and su bstrate and inducer concentrations has been constructed, and its param eters were estimated. An optimal control strategy with three stages of the culture state (growth, inducer synthesis, and growth+product synt hesis) was determined and validated experimentally by optimization of the substrate flow rate in a fed-batch fermentation.