Continuous Production of Thrombomodulin from a Pichia pastoris Fermentation

Abstract

A rotary membrane separation system was used in a continuous fermentation of Pichia pastoris with cell recycling to obtain high cell concentration and high thrombomodulin production. The dilution rates of this continuous fermentation were between 0.25 and 0.35 dm 3 day -1 , and the production process was maintained for 10 days. Since cells were recycled and only part of liquid broth was taken from the system, a very high cell concentration level (248 g dm -3 ) was obtained. The peak protein expression level was at 72 h after methanol induction, was 300 mg dm -3 (3.6 x 10 5 activity unit cm -3 ) and the total harvested supernatant was three times the working volume.