Abstract
Glycan biosynthesis simulation research has progressed remarkably since 1997, when the first mathematical model for N-glycan biosynthesis was proposed. An O-glycan model has also been developed to predict O-glycan biosynthesis pathways in both forward and reverse directions. In this work, we started with a set of O-glycan profiles of CHO cells transiently transfected with various combinations of glycosyltransferases. The aim was to develop a model that encapsulated all the enzymes in the CHO transfected cell lines. Due to computational power restrictions, we were forced to focus on a smaller set of glycan profiles, where we were able to propose an optimized set of kinetics parameters for each enzyme in the model. Using this optimized model we showed that the abundance of more processed glycans could be simulated compared to observed abundance, while predicting the abundance of glycans earlier in the pathway was less accurate. The data generated show that for the accurate prediction of O-linked glycosylation, additional factors need to be incorporated into the model to better reflect the experimental conditions.
Highlights
IntroductionThe value of recombinant proteins as a main therapeutic approach, where human-like proteins are produced in host cells, has been increasing
The first mathematical model for Nglycan biosynthesis was developed in 1997 by Umana and Bailey (UB1997), simulating the initial stages of N-glycan biosynthesis from a single core structure [5]. Their model was built on the basic assumption that the four well-mixed compartments of the Golgi apparatus contain a set of eight glycosyltransferases
The mucin-type O-glycan profile was mapped for each cell line (Supplementary Materials)
Summary
The value of recombinant proteins as a main therapeutic approach, where human-like proteins are produced in host cells, has been increasing The pharmacokinetics of these proteins in the human body vary according to the amino acid sequence, and the glycans attached to the protein during the synthesis process. The first mathematical model for Nglycan biosynthesis was developed in 1997 by Umana and Bailey (UB1997), simulating the initial stages of N-glycan biosynthesis from a single core structure [5] Their model was built on the basic assumption that the four well-mixed compartments of the Golgi apparatus contain a set of eight glycosyltransferases. These enzymes catalyzed 33 reactions and generated 33 different oligosaccharide species of N-linked glycans attached to a specified protein. The model parameters were estimated from the literature describing Chinese
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