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. 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). 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.