Enzymatic Synthesis of Glycans and Glycoconjugates
Glycoconjugates have great potential to improve human health in a multitude of different ways and fields. Prominent examples are human milk oligosaccharides and glycosaminoglycans. The typical choice for the production of homogeneous glycoconjugates is en
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Enzymatic Synthesis of Glycans and Glycoconjugates Thomas Rexer , Dominic Laaf, Johannes Gottschalk , Hannes Frohnmeyer , Erdmann Rapp , and Lothar Elling
Contents 1 Introduction 2 Glycan Synthesis with Leloir Glycosyltransferase 2.1 The Choice of Leloir Glycosyltransferases 2.2 Nucleotide Sugars 3 Practical Application of Enzymatic Glycosylation Reactions 3.1 Glycosaminoglycans: Hyaluronic Acid, Heparan Sulfate, Heparin, Chondroitin Sulfate, Dermatan Sulfate 3.2 Enzymatic Synthesis of Human Milk Oligosaccharides 3.3 Microreactors for Automated Enzymatic Glycan Synthesis 3.4 Glycoconjugate Vaccines 3.5 In Vitro Glycoengineering of Pharma Glycoproteins References
Abstract Glycoconjugates have great potential to improve human health in a multitude of different ways and fields. Prominent examples are human milk oligosaccharides and glycosaminoglycans. The typical choice for the production of homogeneous glycoconjugates is enzymatic synthesis. Through the availability of expression and purification protocols, recombinant Leloir glycosyltransferases are Thomas Rexer and Dominic Laaf contributed equally to this work. T. Rexer and E. Rapp Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg, Department of Bioprocess Engineering, Magdeburg, Germany e-mail: [email protected]; [email protected] D. Laaf, J. Gottschalk, H. Frohnmeyer, and L. Elling (*) Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany e-mail: [email protected]; [email protected]; [email protected]; [email protected]
T. Rexer et al.
widely applied as catalysts for the synthesis of a wide range of glycoconjugates. Extensive utilization of these enzymes also depends on the availability of activated sugars as building blocks. Multi-enzyme cascades have proven a versatile technique to synthesize and in situ regenerate nucleotide sugar. In this chapter, the functions and mechanisms of Leloir glycosyltransferases are revisited, and the advantage of prokaryotic sources and production systems is discussed. Moreover, in vivo and in vitro pathways for the synthesis of nucleotide sugar are reviewed. In the second part, recent and prominent examples of the application of Leloir glycosyltransferase are given, i.e., the synthesis of glycosaminoglycans, glycoconjugate vaccines, and human milk oligosaccharides as well as the re-glycosylation of biopharmaceuticals, and the status of automated glycan assembly is revisited. Graphical Abstract
Keywords Biocatalysis, Glycoconjugates, Glycoengineering, Glycoproteins, Glycosaminoglycans, Glycosyltransferases, Microreactors, Milk Oligosaccharides, Nucleotide sugars
Abbreviations ADP Asp CHO CMP CS CTP DS DSP dTDP FucT GalT
Adenosine diphosphate Asparagine Chinese hamster ovary Cytidine monophosphate Chondroitin sulfate Cytidine triphosphate Dermatan sulfate Downstream processing Deoxythymidine diphosphate Fucosyltransferase Galactosyltrans
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