In this study, we used a bacteriophage λQ - S - mutant that increased the stability of recombinant Escherichia coli during continuous culture. The operation was conducted in two stages: the first stage was carried out to promote cell growth, and the second stage was performed for product formation. The productivity of recombinant proteins depends on the substrate concentration of the fresh medium supplied to the second stage (S 3) and dilution rate of the second stage (D 2). With the optimal value of S 3 and D 2, the first and second stages were stably maintained for 170 and 80 h, respectively. To further improve this process, a three-stage continuous process was conducted with an additional induction stage between the growth and production stages. Compared with the two-stage operation, the stable production period was extended by 1.7 fold, and the recombinant protein production increased by 1.3 fold.
Bibliographical noteFunding Information:
Acknowledgments This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (WCU project R32-2009-000-10213-0, No. 2009-0081997).
- Bacteriophage λQ S mutant
- Continuous operation
- Escherichia coli
- Temperature induction