Alleviation of proteolytic degradation of recombinant human bone morphogenetic protein-4 by repeated batch culture of Chinese hamster ovary cells

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The effects of culture temperature and pH on cell growth and recombinant human bone morphogenetic protein-4 (rhBMP-4) production were investigated to maximize rhBMP-4 production from Chinese hamster ovary cells. Cells were cultivated in a bioreactor at different culture pH levels (6.7, 6.9, 7.2, and 7.5) and temperatures (37 degrees C and 33 degrees C). The highest rhBMP-4 concentration (4.6 +/- 0.5 mu g/mL) was obtained at pH 7.2 and 37 degrees C. Regardless of culture temperature and pH, significant rhBMP-4 degradation via increased proteolytic activity was observed in the decline growth phase. Protease inhibitors such as EDTA and leupeptin were toxic and thus did not enhance rhBMP-4 production. High viability was achieved in repeated batch cultures with frequent medium exchanges. These cultures showed enhanced rhBMP-4 productivity, demonstrating the potential of repeated batch cultures as a means for improved rhBMP-4 production. (C) 2016 Elsevier Ltd. All rights reserved
Publisher
ELSEVIER SCI LTD
Issue Date
2016-08
Language
English
Article Type
Article
Keywords

CHO-CELLS; PROTEASE INHIBITORS; TEMPERATURE; PRODUCTIVITY; ERYTHROPOIETIN; HETEROGENEITY; EXPRESSION; LEVEL; PH; OVEREXPRESSION

Citation

PROCESS BIOCHEMISTRY, v.51, no.8, pp.1078 - 1084

ISSN
1359-5113
DOI
10.1016/j.procbio.2016.05.007
URI
http://hdl.handle.net/10203/213167
Appears in Collection
BS-Journal Papers(저널논문)
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