Optimal Control of Fed‐Batch Fermentation with Autoinduction of Metabolite Production

摘要

AbstractInduction of metabolite production is a common feature of many cultures obtained by recombinant DNA technology. Synthesis of a product in these cultures is triggered by a sharp change in environmental conditions or by autoinduction in which the cells, under conditions of growth limitation, produce a species that initiates the synthesis. If product synthesis is the objective of the fermentation, then the time of induction should be optimized so that enough biomass is produced prior to induction while ample nutrient is left in the broth to sustain product synthesis after induction. In this study, recombinant luminousEscherichia colihas been used to portray an autoinductive culture in batch and fed‐batch fermentations. A model describing the cell density and substrate and inducer concentrations has been constructed, and its parameters were estimated. An optimal control strategy with three stages of the culture state (growth, inducer synthesis, and growth+product synthesis) was determined and validated experimentally by optimization of the substrate flow rate in a fed‐batch fermentat