Use of a cell recycle reactor to increase production of a proteolysis-susceptible peptide secreted from recombinant Saccharomyces cerevisiae.
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.
Salk Institute Biotechnology/Industrial Associates, Inc. (SIBIA), San Diego, CA 92138.
R S
RS
Siegel
R A
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Brierley
D001673:Biodegradation, Environmental; D002453:Cell Cycle; D003001:Cloning, Molecular / Q000379:methods*; D005285:Fermentation; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008433:Mathematics; D008954:Models, Biological; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
D011994:Recombinant Proteins; D013007:Growth Hormone-Releasing Hormone