Generic Model Control Applied to E. coli BL21(DE3) Fed-Batch Cultures

Merouane Abadli,Sihem Tebbani,Didier Dumur,Laurent Dewasme,Alain Vande Wouwer

doi:10.3390/pr8070772

Abstract

This work proposes a Generic Model Control (GMC) strategy to regulate biomass growth in fed-batch cultures of Escherichia coli BL21(DE3). The control law is established using a previously validated mechanistic model based on the overflow metabolism paradigm. A model reduction is carried out to prevent the controller from relying on kinetics, which may be uncertain. In order to limit the controller to the use of a single measurement, i.e., biomass concentration which is readily available, a Kalman filter is designed to reconstruct the nonmeasurable information from the outlet gas and the remaining stoichiometry. Several numerical simulations are presented to assess the controller robustness with respect to model uncertainty. Experimental validation of the proposed GMC strategy is achieved with a lab-scale bioreactor.

Highlights

Industrial production of recombinant proteins is commonly achieved through high cell-density fed-batch fermentation of genetically modified strains of Escherichia coli, with glucose as the main or sole carbon source
The goal of this study is to develop a control strategy to regulate the biomass growth of E. coli
Model reduction is applied to a mechanistic model describing the overflow metabolism

Summary

Introduction

Industrial production of recombinant proteins is commonly achieved through high cell-density fed-batch fermentation of genetically modified strains of Escherichia coli, with glucose as the main or sole carbon source. This is due to the many biological traits of this microorganism, such as the flexible culture conditions, fast growth, the well-known physiological properties, the vast catalog of available tools for genetic and genomic engineering [1], and the high production yields attainable [2]. E. coli growth is either performed under oxygen-limiting conditions or when the capacity for energy generation within the cell is exceeded due to high carbon flux into the main metabolic pathways [3,4]. Several control strategies have been developed for similar fed-batch processes presenting overflow metabolism [8,9,10,11,12]

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