Lactoyl leucine and isoleucine are bioavailable alternatives for canonical amino acids in cell culture media.
bioprocesses
cell culture media
enzymatic cleavage
lactoyl- (iso)leucine
solubility
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
26
02
2021
received:
06
02
2021
accepted:
14
03
2021
pubmed:
20
3
2021
medline:
3
3
2022
entrez:
19
3
2021
Statut:
ppublish
Résumé
Increasing demands for protein-based therapeutics such as monoclonal antibodies, fusion proteins, bispecific molecules, and antibody fragments require researchers to constantly find innovative solutions. To increase yields and decrease costs of next generation bioprocesses, highly concentrated cell culture media formulations are developed but often limited by the low solubility of amino acids such as tyrosine, cystine, leucine, and isoleucine, in particular at physiological pH. This study sought to investigate highly soluble and bioavailable derivatives of leucine and isoleucine that are applicable for fed-batch processes. N-lactoyl-leucine and N-lactoyl-isoleucine sodium salts were tested in cell culture media and proved to be beneficial to increase the overall solubility of cell culture media formulations. These modified amino acids proved to be bioavailable for various Chinese hamster ovary (CHO) cells and were suitable for replacement of canonical amino acids in cell culture feeds. The quality of the final recombinant protein was studied in bioprocesses using the derivatives, and the mechanism of cleavage was investigated in CHO cells. Altogether, both N-lactoyl amino acids represent an advantageous alternative to canonical amino acids to develop highly concentrated cell culture media formulations to support next generation bioprocesses.
Identifiants
pubmed: 33738790
doi: 10.1002/bit.27755
pmc: PMC8453549
doi:
Substances chimiques
Antibodies, Monoclonal
0
Culture Media
0
Recombinant Proteins
0
Isoleucine
04Y7590D77
Leucine
GMW67QNF9C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3395-3408Informations de copyright
© 2021 Merck KGaA. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
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