Avoiding overfeeding in high cell density fed-batch cultures of E. coli during the production of heterologous proteins

摘要

Heterologous protein production often causes a significant metabolic burden in Escherichia coli cells which manifests itself in a substantial decrease in their physiological characteristics such as the maximal specific growth rate on a given substrate, the maximal substrate uptake rate as well as the maximal specific oxygen uptake rate. In high-cell-density cultures, the substrate feed rate must be adapted to this changing capabilities of the cells in order to avoid overfeeding and thus the formation of by-products that inhibit the cell performance further. This requires the precise knowledge about the changes in these specific rates, particularly during the product formation phase.