Use of novel cystine analogs to decrease oxidative stress and control product quality

Valentine Chevallier*, Marvin Zoller, Nadine Kochanowski, Mikael R. Andersen, Christopher T. Workman, Laetitia Malphettes

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Continuous improvements of cell culture media are required in order to ensure high yield and product quality. However, some components can be instable and lead to detrimental effects on bioprocess performances. L-cysteine is an essential amino acid commonly used in cell culture media. Despite its beneficial effect on recombinant protein production, in some cases, this component can be responsible for product microheterogeneity. In this context, alternative components have to be found in order to reduce product variants while maintaining high productivity. In this study, we have assessed the performance of different cysteine and cystine analogs : N-acetyl-cysteine, s-sulfocysteine, N,N'-diacetyl-L-cystine and the N,N'-diacetyl-L-cystine dimethylester (DACDM). Replacement of cysteine by cystine analogs, and especially DACDM, has shown positive impact on charge variants level and recombinant protein coloration level. Moreover, this molecule contributed to the increase of the intracellular glutathione pool, which suggests a close relationship with the oxidative stress regulation.
Original languageEnglish
JournalJournal of Biotechnology
Volume327
Pages (from-to)1-8
Number of pages8
ISSN0168-1656
DOIs
Publication statusPublished - 2021

Keywords

  • CHO cells
  • Cysteine
  • Cell culture media
  • Monoclonal antibody
  • Glutathione
  • Charge variants

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