Cited by 97Viral Infectious Diseases and Gene Expression in InsectsMicrobial Metabolic Engineering and BioproductionMetabolomics and Mass Spectrometry Studies

Metabolomics-driven approach for the improvement of Chinese hamster ovary cell growth: overexpression of malate dehydrogenase II

Chong, William P.K., Reddy, Satty G., Yusufi, Faraaz N.K., Lee, Dong-Yup, Wong, Niki S.C., Heng, Chew Kiat, Yap, Miranda G.S., Ho, Ying Swan·2010·Journal of Biotechnology

Abstract

We have established a liquid chromatography-mass spectrometry based metabolomics platform to identify extracellular metabolites in the medium of recombinant Chinese hamster ovary (CHO) fed-batch reactor cultures. Amongst the extracellular metabolites identified, malate accumulation was the most significant. The contributing factors to malate efflux were found to be the supply of aspartate from the medium, and an enzymatic bottleneck at malate dehydrogenase II (MDH II) in the tricarboxylic acid cycle. Subsequent metabolic engineering to overexpress MDH II in CHO resulted in increases in intracellular ATP and NADH, and up to 1.9-fold improvement in integral viable cell number.

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Crossref · 10.1016/j.jbiotec.2010.03.018

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  • A bottleneck at the malate dehydrogenase II (MDHII) level was characterized for the tricarboxylic acid (TCA) cycle in CHO cells and pyruvate metabolism was shown to vary between high producing and low producing anti-CD20 CHO clones.

    “A bottleneck at the malate dehydrogenase II (MDHII) level was characterized for the tricarboxylic acid (TCA) cycle in CHO cells and pyruvate metabolism was shown to vary between high producing and low producing anti-CD20 CHO clones (Chong et al., 2010;Ghorbaniaghdam et al., 2014).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Chong et al., 2010

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Authors
Chong, W. P. K., Reddy, S. G., Yusufi, F. N. K., Lee, D.-Y., Wong, N. S. C., Heng, C. K., Yap, M. G. S., & Ho, Y. S.
Affiliations
  • Agency for Science, Technology and Research (SG)
  • National University of Singapore (SG)
Corresponding author
Chong, William P.K.
Venue
Journal of Biotechnology
Publisher
Elsevier BV
Published
2010-05-17
Volume
147
Issue
2
Pages
116-121
ISSN
0168-1656 (ISSN-L)
OpenAlex
W2092015535
Cited by
97
References
0
Citations by year
2026: 4 · 2025: 6 · 2024: 5 · 2023: 4 · 2022: 1 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 10 · 2014: 9 · 2013: 9 · 2012: 9
FWCI
3.38
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion)
Funders
Biomedical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
CHO cells, metabolic engineering, extracellular metabolites, malate accumulation, TCA cycle, fed-batch fermentation
MeSH terms
Animals, Aspartic Acid, Cell Count, Chromatography, Liquid, Cricetulus, Cricetinae, Malate Dehydrogenase, Malates, Mass Spectrometry, CHO Cells, Cell Culture Techniques, Cell Growth Processes, Metabolic Networks and Pathways, Metabolomics

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