Synthetic Glycobiotechnology

Synthetic Glycobiotechnology

Motivation

Glycans attached to proteins exert various important biological functions. They serve as recognition targets for glycan binding proteins, modulate the properties of proteins and can stabilize protein folding. One example of their biological significance is the binding of influenza viral particles to terminal sialic acid residues of glycans on the surface of epithelial cells

The importance of protein glycosylation for the biotech industry is highlighted by the fact that approximately 70% of therapeutic proteins, approved or in (pre-)clinical studies, are glycoproteins. However, there is still a lack of thorough scientific understanding of the structure-function relationships of glycans due to macro- and microheterogeneities of biological samples.

The Synthetic Glycobiotechnology group of the bioprocess engineering department develops process platforms for the efficient glycosylation of proteins. The complex design of these platforms integrates protein expression & purification, high-performance and high-resolution metabolite- and glycoanalytics as well as mathematical modelling of multienzyme networks. Therefore, the group closely cooperates with groups in-and outside the bioprocess department.

References

Mahour, R.; Marichal-Gallardo, P.; Rexer, T.; Reichl, U.: Multi-enzyme cascades for the in vitro synthesis of guanosine diphosphate L-fucose. ChemCatChem 13 (8), pp. 1981 - 1989 (2021)
Rexer, T.; Laaf, D.; Gottschalk, J.; Frohnmeyer, H.; Rapp, E.; Elling, L.: Enzymatic Synthesis of Glycans and Glycoconjugates. In: Advances in Biochemical Engineering / Biotechnology, pp. 1 - 50. Springer, Heidelberg (2020)
Rexer, T.; Wenzel, L.; Hoffmann, M.; Tischlik, S.; Bergmann, C.; Grote, V.; Boecker, S.; Bettenbrock, K.; Schildbach, A.; Kottler, R. et al.; Mahour, R.; Rapp, E.; Pietzsch, M.; Reichl, U.: Synthesis of lipid-linked oligosaccharides by a compartmentalized multi-enzyme cascade for the in vitro N-glycosylation of peptides. Journal of Biotechnology 322 (10), pp. 54 - 65 (2020)
Mahour, R.; Klapproth, J.; Rexer, T.; Schildbach, A.; Klamt, S.; Pietzsch, M.; Rapp, E.; Reichl, U.: Establishment of a five-enzyme cell-free cascade for the synthesis of uridine diphosphate N-acetylglucosamine. Journal of Biotechnology 283, pp. 120 - 129 (2018)
Rexer, T.; Schildbach, A.; Klapproth, J.; Schierhorn, A.; Mahour, R.; Pietzsch, M.; Rapp, E.; Reichl, U.: One pot synthesis of GDP-mannose by a multi-enzyme cascade for enzymatic assembly of lipid-linked oligosaccharides. Biotechnology and Bioengineering 115 (1), pp. 192 - 205 (2018)

Patents

[1] R Mahour, TFT Rexer: Enzymatic method for preparation of GDP-fucose. European patent: EP3719135 (A1) (2020).

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