Generic model based control of different specific rates in recombinant E. coli Fed-batch processes

Abstract

In addition to often reported control of the specific growth rate we show in this contribution a novel method to control the biomass specific substrate uptake as well as the protein production rate during the production phase of microbial fed-batch cultures. The control laws base on a calibrated process model including experimental data sets with different constant glycerol feed rates. The model includes changing growth and production behaviour in function of the induced metabolic stress. Based on the method of non-linear feedback linearization, the control laws were derived from the model, using the glycerol feed rate as the manipulable variable. Considering comparable setpoints at three different levels the effectiveness of the controller as well as their potential to improve the production phase was assessed by simulations. The direct control of product formation rates enables to ensure constant production performance and therefore to reach highest product levels in short time. As a drawback, the controller needs high feed adaption towards the end to counteract the advancing decay of the attainable production rates. This, to a lesser extend, also applies for the growth rate. A constant substrate uptake rate resulted in a valuable alternative to a uncontrolled, constant feed rate during the production phase of recombinant protein production processes.