Metabolite profiling of CHO cells with different growth characteristics

Stefanie Dietmair, Mark P. Hodson, Lake Ee Quek, Nicholas E. Timmins, Panagiotis Chrysanthopoulos, Shana S. Jacob, Peter Gray, Lars K. Nielsen

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Mammalian cell cultures are the predominant system for the production of recombinant proteins requiring post-translational modifications. As protein yields are a function of growth performance (among others), and performance varies greatly between culture medium (e.g., different growth rates and peak cell densities), an understanding of the biological mechanisms underpinning this variability would facilitate rational medium and process optimization, increasing product yields, and reducing costs. We employed a metabolomics approach to analyze differences in metabolite concentrations of CHO cells cultivated in three different media exhibiting different growth rates and maximum viable cell densities. Analysis of intra- and extracellular metabolite concentrations over the course of the cultures using a combination of HPLC and GC-MS, readily detected medium specific and time dependent changes. Using multivariate data analysis, we identified a range of metabolites correlating with growth rate, illustrating how metabolomics can be used to relate gross phenotypic changes to the fine details of cellular metabolism.

Original languageEnglish
Pages (from-to)1404-1414
Number of pages11
JournalBiotechnology and Bioengineering
Volume109
Issue number6
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Fingerprint

CHO Cells
Metabolites
Metabolomics
Growth
Recombinant proteins
Cell Count
Cell culture
Recombinant Proteins
Metabolism
Culture Media
Post Translational Protein Processing
Proteins
Multivariate Analysis
Cell Culture Techniques
High Pressure Liquid Chromatography
Costs and Cost Analysis
Costs

Keywords

  • CHO cells
  • Media
  • Metabolomics

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Dietmair, S., Hodson, M. P., Quek, L. E., Timmins, N. E., Chrysanthopoulos, P., Jacob, S. S., ... Nielsen, L. K. (2012). Metabolite profiling of CHO cells with different growth characteristics. Biotechnology and Bioengineering, 109(6), 1404-1414. https://doi.org/10.1002/bit.24496

Metabolite profiling of CHO cells with different growth characteristics. / Dietmair, Stefanie; Hodson, Mark P.; Quek, Lake Ee; Timmins, Nicholas E.; Chrysanthopoulos, Panagiotis; Jacob, Shana S.; Gray, Peter; Nielsen, Lars K.

In: Biotechnology and Bioengineering, Vol. 109, No. 6, 06.2012, p. 1404-1414.

Research output: Contribution to journalArticle

Dietmair, S, Hodson, MP, Quek, LE, Timmins, NE, Chrysanthopoulos, P, Jacob, SS, Gray, P & Nielsen, LK 2012, 'Metabolite profiling of CHO cells with different growth characteristics', Biotechnology and Bioengineering, vol. 109, no. 6, pp. 1404-1414. https://doi.org/10.1002/bit.24496
Dietmair S, Hodson MP, Quek LE, Timmins NE, Chrysanthopoulos P, Jacob SS et al. Metabolite profiling of CHO cells with different growth characteristics. Biotechnology and Bioengineering. 2012 Jun;109(6):1404-1414. https://doi.org/10.1002/bit.24496
Dietmair, Stefanie ; Hodson, Mark P. ; Quek, Lake Ee ; Timmins, Nicholas E. ; Chrysanthopoulos, Panagiotis ; Jacob, Shana S. ; Gray, Peter ; Nielsen, Lars K. / Metabolite profiling of CHO cells with different growth characteristics. In: Biotechnology and Bioengineering. 2012 ; Vol. 109, No. 6. pp. 1404-1414.
@article{2b1ce34966ab4016b7eb4f4366288f57,
title = "Metabolite profiling of CHO cells with different growth characteristics",
abstract = "Mammalian cell cultures are the predominant system for the production of recombinant proteins requiring post-translational modifications. As protein yields are a function of growth performance (among others), and performance varies greatly between culture medium (e.g., different growth rates and peak cell densities), an understanding of the biological mechanisms underpinning this variability would facilitate rational medium and process optimization, increasing product yields, and reducing costs. We employed a metabolomics approach to analyze differences in metabolite concentrations of CHO cells cultivated in three different media exhibiting different growth rates and maximum viable cell densities. Analysis of intra- and extracellular metabolite concentrations over the course of the cultures using a combination of HPLC and GC-MS, readily detected medium specific and time dependent changes. Using multivariate data analysis, we identified a range of metabolites correlating with growth rate, illustrating how metabolomics can be used to relate gross phenotypic changes to the fine details of cellular metabolism.",
keywords = "CHO cells, Media, Metabolomics",
author = "Stefanie Dietmair and Hodson, {Mark P.} and Quek, {Lake Ee} and Timmins, {Nicholas E.} and Panagiotis Chrysanthopoulos and Jacob, {Shana S.} and Peter Gray and Nielsen, {Lars K.}",
year = "2012",
month = "6",
doi = "10.1002/bit.24496",
language = "English",
volume = "109",
pages = "1404--1414",
journal = "Biotechnology and Bioengineering",
issn = "0006-3592",
publisher = "Wiley-VCH Verlag",
number = "6",

}

TY - JOUR

T1 - Metabolite profiling of CHO cells with different growth characteristics

AU - Dietmair, Stefanie

AU - Hodson, Mark P.

AU - Quek, Lake Ee

AU - Timmins, Nicholas E.

AU - Chrysanthopoulos, Panagiotis

AU - Jacob, Shana S.

AU - Gray, Peter

AU - Nielsen, Lars K.

PY - 2012/6

Y1 - 2012/6

N2 - Mammalian cell cultures are the predominant system for the production of recombinant proteins requiring post-translational modifications. As protein yields are a function of growth performance (among others), and performance varies greatly between culture medium (e.g., different growth rates and peak cell densities), an understanding of the biological mechanisms underpinning this variability would facilitate rational medium and process optimization, increasing product yields, and reducing costs. We employed a metabolomics approach to analyze differences in metabolite concentrations of CHO cells cultivated in three different media exhibiting different growth rates and maximum viable cell densities. Analysis of intra- and extracellular metabolite concentrations over the course of the cultures using a combination of HPLC and GC-MS, readily detected medium specific and time dependent changes. Using multivariate data analysis, we identified a range of metabolites correlating with growth rate, illustrating how metabolomics can be used to relate gross phenotypic changes to the fine details of cellular metabolism.

AB - Mammalian cell cultures are the predominant system for the production of recombinant proteins requiring post-translational modifications. As protein yields are a function of growth performance (among others), and performance varies greatly between culture medium (e.g., different growth rates and peak cell densities), an understanding of the biological mechanisms underpinning this variability would facilitate rational medium and process optimization, increasing product yields, and reducing costs. We employed a metabolomics approach to analyze differences in metabolite concentrations of CHO cells cultivated in three different media exhibiting different growth rates and maximum viable cell densities. Analysis of intra- and extracellular metabolite concentrations over the course of the cultures using a combination of HPLC and GC-MS, readily detected medium specific and time dependent changes. Using multivariate data analysis, we identified a range of metabolites correlating with growth rate, illustrating how metabolomics can be used to relate gross phenotypic changes to the fine details of cellular metabolism.

KW - CHO cells

KW - Media

KW - Metabolomics

UR - http://www.scopus.com/inward/record.url?scp=84859886034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859886034&partnerID=8YFLogxK

U2 - 10.1002/bit.24496

DO - 10.1002/bit.24496

M3 - Article

VL - 109

SP - 1404

EP - 1414

JO - Biotechnology and Bioengineering

JF - Biotechnology and Bioengineering

SN - 0006-3592

IS - 6

ER -