Glycoengineering and Modeling of Protein N-Glycosylation
Abstract Glycoproteins for treating human diseases have revolutionized the health care industry. However, controlling glycosylation has been a challenge as small variations in glycan structure can be responsible for significant changes in key therapeutic properties. Manipulation of glycan biosynthesis can be particularly complex since the process is not directly encoded on the genome but depends on multiple variables such as enzymes’ activity, selectivity, localization, expression host, and process parameters and conditions. Furthermore, a particular glycoprotein may include many different glycan structures due to differences in processing that occur for each individual molecule. The present chapter focuses on experimental and computational approaches to direct N-glycosylation in expression systems for generation of biotherapeutics of superior value. Glycoengineering-based manipulations of glycan structures using glycosyltransferases, modification of precursor biosynthetic pathways, and predictions of glycosylation patterns using mathematical models are described including examples from the literature as a means of optimizing glycoform distributions in cells.
This work was supported by Award Number 5R41CA127885-02 from the National Cancer Institute.
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