Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism

Martinez, Verónica S., Buchsteiner, Maria, Gray, Peter, Nielsen, Lars K. and Quek, Lake-Ee (2015) Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism. Metabolic Engineering Communications, 2 46-57. doi:10.1016/j.meteno.2015.06.001


Author Martinez, Verónica S.
Buchsteiner, Maria
Gray, Peter
Nielsen, Lars K.
Quek, Lake-Ee
Title Dynamic metabolic flux analysis using B-splines to study the effects of temperature shift on CHO cell metabolism
Journal name Metabolic Engineering Communications   Check publisher's open access policy
ISSN 2214-0301
Publication date 2015-12
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.meteno.2015.06.001
Open Access Status DOI
Volume 2
Start page 46
End page 57
Total pages 12
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2016
Language eng
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.
Keyword B-spline curve fitting
CHO cells
Dynamic
Flux analysis
Metabolism
Temperature shift
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
 
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