Continuous production of human leukocyte interferon withEscherichia coli and continuous cell lysis in a two stage chemostat

Abstract

The continuous production and extrac-tion of human leukocyte interferon (type α2) in a two stage chemostat is described. Interferon con-tainingEscherichia coli cells were produced in the first stage and transferred to the second stage, where the cells were lysed continuously by the ad-dition of ampicillin. The medium used was based on corn steep liquor. Highest interferon titres and the best extraction efficiencies were achieved when running the first and second stages at dilution rates of 0.3 h−1 and 0.1 h−1, and at temperatures of 30° C and 25 °C, respectively. In order to prevent loss of interferon in the second stage, oxygen limitation had to be avoided. For optimal cell lysis there should be excess glucose in the second stage and the ampicillin concentration should be maintained above 100 mg 1−1.