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

摘要

A model-based adaptive linearizing control law was derived for the regulationof the acetate concentration during the fed-batch fermentation of recombinant proteinswith 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 onacetate, and maintenance. A model order reduction method was used to allow thedevelopment of the control algorithm without the knowledge of the kinetic structure beingnecessary. The non-linear model was subjected to transformations in order to obtain alinear 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 ratesmeasurements. Acetate measurements are achieved with a developed Flow InjectionAnalysis (FIA) physical-chemical method. The gas transfer rates are calculated from gasanalysis data obtained with a Mass Spectrometer (MS) connected to the exhaust gas lineof the fermenter and also to the inlet aeration line. These calculations, as well as theimplementation of the control law were performed through a MATLAB script embeddedin a LABView program that also acquired data from the FIA system and other relevantstate variables from the fermenter Digital Control Unit.Copyright 2002 IFAC