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Real-time monitoring of glycerol and methanol to enhance antibody production in industrial Pichia pastoris bioprocesses.
- Source :
-
Biochemical Engineering Journal . Feb2015, Vol. 94, p115-124. 10p. - Publication Year :
- 2015
-
Abstract
- Monoclonal antibody production in glycoengineered Pichia pastoris was optimized for high cell density fed-batch fermentations. Results show that antibody productivity was 1.72-fold higher when maintaining oxygen-limited conditions compared to methanol-limited conditions during the protein production phase of the bioprocess. Under oxygen-limited conditions with a 30 mmol L −1 h −1 of oxygen uptake rate, an optimum methanol dosage level of 10 gL −1 was established by comparing antibody titers under different methanol dosages during protein production. Real-time on-line NIR monitoring of glycerol concentration, methanol concentration, and relative cell density provided valuable data for process characterization and optimization. Real-time profiles of glycerol concentration and relative cell density documented run-to-run consistency during the batch and fed-batch phases by analyses of the glycerol consumption and cell growth kinetics. The volumetric methanol consumption rate was characterized for the induction process following the end of the glycerol fed-batch phase. Under oxygen-limited conditions, the volumetric methanol consumption rate increased over a 60-h period and this increase was independent of the methanol concentration over a range of 2.5–30 gL −1 when the oxygen utilization rate was maintained at 30 mmol L −1 h −1 . Utility of the on-line NIR monitor is demonstrated over the one-year period of this investigation by accurately tracking biomass, glycerol concentration, and methanol concentration without user required recalibration as well as by documenting abnormal events during high cell density bioprocesses. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1369703X
- Volume :
- 94
- Database :
- Academic Search Index
- Journal :
- Biochemical Engineering Journal
- Publication Type :
- Academic Journal
- Accession number :
- 100156175
- Full Text :
- https://doi.org/10.1016/j.bej.2014.12.002