Document Detail

Kinetics and stability of GM-CSF production by recombinant yeast cells immobilized in a fibrous-bed bioreactor.
MedLine Citation:
PMID:  8987473     Owner:  NLM     Status:  MEDLINE    
The continuous production of murine granulocyte-macrophage colony-stimulating factor (GM-CSF) by recombinant yeast cells immobilized in a fibrous-bed bioreactor was studied. A high cell density of approximately 68 g/L and a GM-CSF productivity of approximately 3.5 mg/L.h were attained in the fibrous-bed bioreactor-fed with a rich (nonselective, pH 6.7) medium at a dilution rate of 0.16 h-1. The GM-CSF production was stable even though the fraction of plasmid-carrying cells in the reactor effluent gradually dropped below 5% over a period of 2 weeks. At the end of that period, the immobilized cells in the fibrous matrix still had a high fraction, approximately 26%, of plasmid-carrying cells. Similar results were obtained with reactors operated at 0.05 h-1 dilution rate and pH 4.0. Although the GM-CSF production was lower at pH 4, the reactor was stably operated for over 4 weeks without contamination or significant loss of productivity. The stable long-term GM-CSF production from the fibrous-bed bioreactor was attributed to the effect of cell immobilization on plasmid stability. Because GM-CSF production was growth-associated, as was found in batch fermentation with free cells, this stabilization effect cannot be attributed solely to the reduced cell growth in the immobilized cell environment. Plasmid-carrying cells were preferentially retained in the fibrous matrix, perhaps because their abilities to adhere to the fiber surface and to form cell aggregates were higher than those of plasmid-free cells.
S T Yang; C H Shu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biotechnology progress     Volume:  12     ISSN:  8756-7938     ISO Abbreviation:  Biotechnol. Prog.     Publication Date:    1996 Jul-Aug
Date Detail:
Created Date:  1997-02-13     Completed Date:  1997-02-13     Revised Date:  2006-05-01    
Medline Journal Info:
Nlm Unique ID:  8506292     Medline TA:  Biotechnol Prog     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  449-56     Citation Subset:  B    
Department of Chemical Engineering, Ohio State University, Columbus 43210, USA.
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MeSH Terms
Cells, Immobilized
Colony-Stimulating Factors, Recombinant / biosynthesis*
Culture Media
Ethanol / chemistry,  metabolism
Glucose / chemistry,  metabolism
Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis*
Microscopy, Electron, Scanning
Plasmids / genetics
Recombination, Genetic
Saccharomyces cerevisiae / genetics,  metabolism*,  ultrastructure
Reg. No./Substance:
0/Colony-Stimulating Factors, Recombinant; 0/Culture Media; 50-99-7/Glucose; 64-17-5/Ethanol; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

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