Optimization of fermentation processes using recombinant Escherichia coli with the cloned trp operon

Abstract

Optimal operating conditions have been determined for recombinant Escherichia coli cells in a fed-batch and two-stage continuous fermentors. The model expression system used in this article was the E. coli trp promoter cloned on plasmids. Model equations for cell growth and cloned-gene expression have been formulated and used to evaluate process performances under different operating modes. The operating variables manipulated for maximum performance include the timing of IAA addition to derepress transcription from the trp promoter. The total operating period and the nutrient concentration profile during fermentations. For a fed-batch mode, the performance was significantly improved by adjusting the IAA addition (environmental switch) time relative to the total operation period. It was found that the optimal switching time exists for a given total operation period. For a two-stage continuous fermentation system, the productivity is more sensitive to the combination of the dilution rates than to the volume ratio of two reactors. In general, as long as the down time is less than the total operation time in the fed-batch mode, the fed-batch mode gives higher productivity than the two-stage continuous system.