Dissecting N-Glycosylation Dynamics in Chinese Hamster Ovary Cells Fed-batch Cultures using Time Course Omics Analyses.
Industrial Biotechnology
Metabolomics
Process Biotechnology
Transcriptomics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
22 Feb 2019
22 Feb 2019
Historique:
received:
30
07
2018
revised:
19
11
2018
accepted:
03
01
2019
pubmed:
27
1
2019
medline:
27
1
2019
entrez:
26
1
2019
Statut:
ppublish
Résumé
N-linked glycosylation affects the potency, safety, immunogenicity, and pharmacokinetic clearance of several therapeutic proteins including monoclonal antibodies. A robust control strategy is needed to dial in appropriate glycosylation profile during the course of cell culture processes accurately. However, N-glycosylation dynamics remains insufficiently understood owing to the lack of integrative analyses of factors that influence the dynamics, including sugar nucleotide donors, glycosyltransferases, and glycosidases. Here, an integrative approach involving multi-dimensional omics analyses was employed to dissect the temporal dynamics of glycoforms produced during fed-batch cultures of CHO cells. Several pathways including glycolysis, tricarboxylic citric acid cycle, and nucleotide biosynthesis exhibited temporal dynamics over the cell culture period. The steps involving galactose and sialic acid addition were determined as temporal bottlenecks. Our results show that galactose, and not manganese, is able to mitigate the temporal bottleneck, despite both being known effectors of galactosylation. Furthermore, sialylation is limited by the galactosylated precursors and autoregulation of cytidine monophosphate-sialic acid biosynthesis.
Identifiants
pubmed: 30682623
pii: S2589-0042(19)30006-9
doi: 10.1016/j.isci.2019.01.006
pmc: PMC6352710
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102-120Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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