Compartmental Glycosylation Flux Analysis. Issue 3 (2021)

• Record Type: Journal Article
• Authors: Aggarwal, Shilpi; Qi, Xin; Neelamegham, Sriram; Gunawan, Rudiyanto
• Is Part Of: IFAC-PapersOnLine. Volume 54:Issue 3(2021)
• Page Start: 287
• Page End: 293
• Publication Date: 2021
• Subjects: glycosylation -- flux analysis -- monoclonal antibodies -- Chinese hamster ovary; Automatic control -- Periodicals; 629.805
• DOI: 10.1016/j.ifacol.2021.08.256
• Languages: English
• ISSNs: 2405-8963

Abstract

Abstract: N-linked glycosylation is a critical quality attribute of therapeutic monoclonal antibodies (mAbs) – an important class of biologics. In this work, we developed compartmental Glycosylation Flux Analysis (cGFA) to enable a more accurate representation of the cell's Golgi apparatus (GA), where protein glycosylation takes place, in the analysis of intracellular fluxes of glycosylation reactions. The application of one-compartment and two-compartment cGFA to a Chinese hamster ovary cell culture production of immunoglobulin G demonstrated the insufficiency of modeling the GA as one well-mixed compartment. The two-compartment cGFA was able to, not only fit the data significantly better than the one-compartment cGFA, but also accurately predict the localization of enzyme in the GA cisternae. Information on glycosylation alterations during cell cultivation, as provided by the cGFA, may lead to a better understanding of how different cell culture parameters control the N-linked glycosylation which would enable a more precise glycoengineering of therapeutic mAbs.