Model-based adaptive control of acetate concentration during the production of recombinant proteins with E. coli

Abstract

A model-based adaptive linearizing control law was derived for the regulation of the acetate concentration during the fed-batch fermentation of recombinant proteins with high cell density culture of Escherichia coli growing on glucose. An unstructured model for the growth was applied to the major metabolic pathways: oxidative growth on glucose, fermentative growth on glucose, oxidative growth on acetate, and maintenance. A model order reduction method was used to allow the development of the control algorithm without the knowledge of the kinetic structure being necessary. The non-linear model was subjected to transformations in order to obtain a linear behaviour for the control loop when a non-linear control is applied. The control law requires on-line acetate and carbon dioxide and oxygen transfer rates measurements. Acetate measurements are achieved with a developed Flow Injection Analysis (FIA) physical-chemical method. The gas transfer rates are calculated from gas analysis data obtained with a Mass Spectrometer (MS) connected to the exhaust gas line of the fermenter and also to the inlet aeration line. These calculations, as well as the implementation of the control law were performed through a MATLAB script embedded in a LABView program that also acquired data from the FIA system and other relevant state variables from the fermenter Digital Control Unit. Copyright 2002 IFAC