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Enzymatic Synthesis of Glycans and Glycoconjugates

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Advances in Glycobiotechnology

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 175))

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 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.

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Abbreviations

ADP:

Adenosine diphosphate

Asp:

Asparagine

CHO:

Chinese hamster ovary

CMP:

Cytidine monophosphate

CS:

Chondroitin sulfate

CTP:

Cytidine triphosphate

DS:

Dermatan sulfate

DSP:

Downstream processing

dTDP:

Deoxythymidine diphosphate

FucT:

Fucosyltransferase

GalT:

Galactosyltransferase

GDP:

Guanosine diphosphate

Glc:

Glucose

GlcA:

Glucuronic acid

GlcNAc:

N-acetylglucosamine

GRAS:

Generally recognized as safe

GT:

Glycosyltransferase

HMO:

Human milk oligosaccharide

HMW:

High-molecular-weight

HNK:

Human natural killer cell

Hp:

Heparin sulfate

HS:

Heparan sulfate

IdoA:

Iduronic acid

IgG:

Immunoglobulin G

LacNAc:

N-Acetyl-D-lactosamine

LMW:

Low-molecular-weight

LNT II:

Lacto-N-triose

Man:

Mannose

MBP:

Maltose-binding protein

MP-CE:

Multiplexed capillary electrophoresis

NDP:

Nucleoside diphosphate

Neu5Ac:

N-Acetylneuraminic acid

NMPK:

Nucleoside monophosphate kinase

NMP:

Nucleoside monophosphate

OPME:

One-pot multi-enzyme

OST:

Oligosaccharyltransferase

PEP:

Phosphoenolpyruvate

PG:

Proteoglycans

PGCS:

Proteoglycan carrying chondroitin sulfate

PGDS:

Proteoglycan carrying dermatan sulfate

PGHS:

Proteoglycan carrying heparan sulfate

PK:

Pyruvate kinase

PPK:

Polyphosphate kinase

PolyP:

Polyphosphate

Ser:

Serine

SiaT:

Sialyltransferase

STY:

Space-time yield

SuSy:

Sucrose synthase

TTN:

Total turnover numbers

UDP:

Uridine diphosphate

UTP:

Uridine triphosphate

Xyl:

Xylose

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  1. Thomas Rexer and Dominic Laaf contributed equally to this work.

Authors and Affiliations

  1. Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg, Department of Bioprocess Engineering, Magdeburg, Germany

    Thomas Rexer

  2. Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany

    Erdmann Rapp

  3. glyXera GmbH, Magdeburg, Germany

    Erdmann Rapp

  4. Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany

    Dominic Laaf, Johannes Gottschalk, Hannes Frohnmeyer & Lothar Elling

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  1. Bioprocess Engineering, Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany

    Erdmann Rapp  & Udo Reichl  & 

  2. glyXera GmbH, Magdeburg, Germany

    Erdmann Rapp

  3. Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    Udo Reichl

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Rexer, T., Laaf, D., Gottschalk, J., Frohnmeyer, H., Rapp, E., Elling, L. (2020). Enzymatic Synthesis of Glycans and Glycoconjugates. In: Rapp, E., Reichl, U. (eds) Advances in Glycobiotechnology. Advances in Biochemical Engineering/Biotechnology, vol 175. Springer, Cham. https://doi.org/10.1007/10_2020_148

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