Metabolic load of recombinant protein production: inhibition of cellular capacities for glucose uptake and respiration after induction of a heterologous gene in Escherichia coli

Abstract

The strong expression of recombinant proteins in bacteria affects the primary carbon and energy metabolism resulting in growth inhibition and acetate formation. By applying glucose pulses to fed-batch fermentations performed for production of a heterologous (alpha-glucosidase in Escherichia coli, we show that the induction of the recombinant gene strongly inhibits the maximum specific uptake capacities for glucose and the respiration capacity. The accumulation of glucose in the fermentation medium promotes the growth of plasmid-free cells. These inhibition effects are well described by including the kinetics of product formation into a recently published dynamic model (Lin et al. [2001] Biotechnol Bioeng 73:349-357). The new model also includes the population characteristics and gives a good fit to the measured data describing growth, production, substrate consumption, by-product formation, and respiration.