Glycosylation flux analysis reveals dynamic changes of intracellular glycosylation flux distribution in Chinese hamster ovary fed-batch cultures

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F17%3A43914750" target="_blank" >RIV/60461373:22340/17:43914750 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S1096717617300964" target="_blank" >https://www.sciencedirect.com/science/article/pii/S1096717617300964</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ymben.2017.07.005" target="_blank" >10.1016/j.ymben.2017.07.005</a>

Result language

angličtina

Original language name

Glycosylation flux analysis reveals dynamic changes of intracellular glycosylation flux distribution in Chinese hamster ovary fed-batch cultures

Original language description

N-linked glycosylation of proteins has both functional and structural significance. Importantly, the glycan structure of a therapeutic protein influences its efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. In this work, we developed glycosylation flux analysis (GFA) for predicting intracellular production and consumption rates (fluxes) of glycoforms, and applied this analysis to CHO fed-batch immunoglobulin G (IgG) production using two different media compositions, with and without additional manganese feeding. The GFA is based on a constraint-based modeling of the glycosylation network, employing a pseudo steady state assumption. While the glycosylation fluxes in the network are balanced at each time point, the GFA allows the fluxes to vary with time by way of two scaling factors: (1) an enzyme-specific factor that captures the temporal changes among glycosylation reactions catalysed by the same enzyme, and (2) the cell specific productivity factor that accounts for the dynamic changes in the IgG production rate. The GFA of the CHO fed-batch cultivations showed that regardless of the media composition, galactosylation fluxes decreased with the cultivation time more significantly than the other glycosylation reactions. Furthermore, the GFA showed that the addition of Mn, a cofactor of galactosyltransferase, has the effect of increasing the galactosylation fluxes but only during the beginning of the cultivation period. The results thus demonstrated the power of the GFA in delineating the dynamic alterations of the glycosylation fluxes by local (enzyme-specific) and global (cell specific productivity) factors.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

20401 - Chemical engineering (plants, products)

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Metabolic Engineering

ISSN

1096-7176

e-ISSN

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Volume of the periodical

43

Issue of the periodical within the volume

Part A

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

9-20

UT code for WoS article

000410479600002

EID of the result in the Scopus database

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