Design and Adaptation of Robust Feeding Profiles for Recombinant E.coli Fed-batch Cultivation Processes*

Abstract

In this paper, the experimental data-based procedure for design and adaptation of robust feeding profiles for recombinant E.coli fed-batch cultivation processes has been proposed. In the first step of the procedure, a maximum glucose consumption rate in biomass growth and target protein production phases must be determined using data from an unlimited growth cultivation. Afterwards, various scenarios for glucose feeding rate need to be designed by setting different levels of glucose consumption rate limitation during the cultivation process. Then the procedure includes the realization of these planned cultivation experiments. The experiments provide the opportunity to select robust and efficient glucose feeding profiles, which then are recommended for implementation in recombinant protein production processes. The proposed procedure also includes a method for adaptation of the designed feeding profile for the case when the process disturbances are significant and glucose begins to accumulate unpredictably in the cultivation medium. The proposed procedure has been tested in simulation studies using the virtual bioreactor approach. The simulation tests have shown the efficiency of the proposed procedure. For the realization of the proposed procedure, a required software has been developed and is being prepared for implementation in industrial PLC.