Use of Fed-Batch Cultivation for Achieving High Cell Densities for the Pilot-Scale Production of a Recombinant Protein (Phenylalanine Dehydrogenase)in Escherichia coli

摘要

A fed-batch process for the high cell density cultivation of E.coli TGl and the production of the recombinant protein phenylalanine dehydrogenase (PheDH)was developed.A model based on Monod kinetics with overflow metabolism and incorporating acetate utilization kinetics was used to generate simulations that describe cell growth,acetate production and reconsumption,and glucose consumption during fed-batch cultivation.Using these simulations a predetermined feeding profile was elaborated that would maintain carbon-limited growth at a growth rate below the critical growth rate for acetate formation (mu