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Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism.
- Source :
-
Metabolic engineering communications [Metab Eng Commun] 2015 Jun 19; Vol. 2, pp. 46-57. Date of Electronic Publication: 2015 Jun 19 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Metabolic flux analysis (MFA) is widely used to estimate intracellular fluxes. Conventional MFA, however, is limited to continuous cultures and the mid-exponential growth phase of batch cultures. Dynamic MFA (DMFA) has emerged to characterize time-resolved metabolic fluxes for the entire culture period. Here, the linear DMFA approach was extended using B-spline fitting (B-DMFA) to estimate mass balanced fluxes. Smoother fits were achieved using reduced number of knots and parameters. Additionally, computation time was greatly reduced using a new heuristic algorithm for knot placement. B-DMFA revealed that Chinese hamster ovary cells shifted from 37 °C to 32 °C maintained a constant IgG volume-specific productivity, whereas the productivity for the controls peaked during mid-exponential growth phase and declined afterward. The observed 42% increase in product titer at 32 °C was explained by a prolonged cell growth with high cell viability, a larger cell volume and a more stable volume-specific productivity.<br /> (© 2015 The Authors.)
Details
- Language :
- English
- ISSN :
- 2214-0301
- Volume :
- 2
- Database :
- MEDLINE
- Journal :
- Metabolic engineering communications
- Publication Type :
- Academic Journal
- Accession number :
- 34150508
- Full Text :
- https://doi.org/10.1016/j.meteno.2015.06.001