Error propagation in constraint-based modeling of Chinese hamster ovary cells
- Author(s)
- Diana Széliová, Dmytro Iurashev, David E. Ruckerbauer, Gunda Koellensperger, Nicole Borth, Michael Melcher, Jurgen Zanghellini
- Abstract
Chinese hamster ovary (CHO) cells are the most popular mammalian cell factories for the production of glycosylated biopharmaceuticals. To further increase titer and productivity and ensure product quality, rational system-level engineering strategies based on constraint-based metabolic modeling, such as flux balance analysis (FBA), have gained strong interest. However, the quality of FBA predictions depends on the accuracy of the experimental input data, especially on the exchange rates of extracellular metabolites. Yet, it is not standard practice to devote sufficient attention to the accurate determination of these rates. In this work, we investigated to what degree the sampling frequency during a batch culture and the measurement errors of metabolite concentrations influence the accuracy of the calculated exchange rates and further, how this error then propagates into FBA predictions of growth rates. We determined that accurate measurements of essential amino acids with low uptake rates are crucial for the accuracy of FBA predictions, followed by a sufficient number of analyzed time points. We observed that the measured difference in growth rates of two cell lines can only be reliably predicted when both high measurement accuracy and sampling frequency are ensured.
- Organisation(s)
- Department of Analytical Chemistry, Mass Spectrometry Centre
- External organisation(s)
- University of Natural Resources and Life Sciences, acib – Austrian Centre of Industrial Biotechnology
- Journal
- Biotechnology Journal
- Volume
- 16
- No. of pages
- 11
- ISSN
- 1860-6768
- DOI
- https://doi.org/10.1002/biot.202000320
- Publication date
- 04-2021
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 304005 Medical biotechnology, 106002 Biochemistry, 106022 Microbiology
- Keywords
- ASJC Scopus subject areas
- Applied Microbiology and Biotechnology, Molecular Medicine
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/error-propagation-in-constraintbased-modeling-of-chinese-hamster-ovary-cells(b7a6d2d1-919f-4c18-ade0-60ef8d22fda5).html