Abstract
Operation of a continuous microbial fermentor with cell recycle can significantly reduce degradation-associated loss of a secreted protein product. Under continuous fermentation conditions, proteolysis of a recombinant growth hormone releasing factor (GRF) analog secreted by S. cerevisiae was first order with respect to GRF concentration. The maximal GRF concentration was increased from 5 mg/l to 30 mg/l by the use of a cell recycle reactor, and volumetric productivity was increased more than 10-fold to an average of 10 mg/l−1/h−1. A mathematical model shows that increased productivity in the cell recycle reactor results from a reduced degradation rate and a shorter residence time of the product in the fermentor.
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Siegel, R., Brierley, R. Use of a Cell Recycle Reactor to Increase Production of a Proteolysis-Susceptible Peptide Secreted from Recombinant Saccharomyces cerevisiae. Nat Biotechnol 8, 639–643 (1990). https://doi.org/10.1038/nbt0790-639
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DOI: https://doi.org/10.1038/nbt0790-639