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The Golgi Glycan Factory (GGF) – Enzymatic Synthesis of Glycoconjugates


Abstract

Laboratory for Biomaterials, Institute for Biotechnology and Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstr. 20, 52074 Aachen, Germany

Glycans and glycoconjugates (glycoproteins, glycolipids, glycosaminoglycans) are relevant for many biomedical applications. The translation of multi-enzyme glycoconjugate synthesis into a larger scale is hampered by multi-parameter optimization of enzyme modules. Using Leloir-glycosyltransferases for glycan synthesis, nucleotide sugars are considered as a bottleneck and expensive substrates. In the Golgi Glycan Factory (GGF), we have set up modular multi-enzyme cascades for the synthesis of sixteen different nucleotide sugars starting from monosaccharides and sucrose as substrates. With these basic technologies, nucleotide sugars are readily available for Leloir-glycosyltransferase cascades, automated enzymatic glycan synthesis, and in vitro one-pot synthesis of high molecular weight hyaluronic acid.

J. Gottschalk, M. Aßmann, J. Kuballa, L. Elling, ChemSusChem 2021, 14, https://doi.org/10.1002/cssc.202101071.
J. Gottschalk, L. Blaschke, M. Aßmann, J. Kuballa, L. Elling, ChemCatChem 2021, 13, 3074-3083.
J. Gottschalk, H. Zaun, A. Eisele, J. Kuballa, L. Elling, Internat. J. Mol. Sci. 2019, 20, 5664.
A. Eisele, H. Zaun, J. Kuballa, L. Elling, ChemCatChem 2018, 10, 2969-2981.
R. Heinzler, T. Fischöder, L. Elling, M. Franzreb, Adv. Synth. Catal. 2019, 361, 4506-4516.
T. Fischöder, S. Cajic, V. Grote, R. Heinzler, U. Reichl, M. Franzreb, E. Rapp, L. Elling, Molecules 2019, 24, 3482.
T. Fischöder, C. Wahl, C. Zerhusen, L. Elling, Biotechnol J 2019, 14, doi:10.1002/biot.201800386.

 

Prof. dr. Lothar Elling

 

 

Laboratory for Biomaterials
Institute for Biotechnology and
Helmholtz-Institute for Biomedical Engineering
RWTH Aachen University
Pauwelsstr. 20, D-52074 Aachen, Germany
Tel: +49-241-8028350
Fax: +49-241-8022387
E-mail: L [kropka] Ellingatbiotec [kropka] rwth-aachen [kropka] de
https://www.biotec-biomat.rwth-aachen.de

 

Lothar Elling is Head of the Laboratory for Biomaterials and a member of the Directors Board in the Helmholtz-Institute for Biomedical Engineering. His research focus lies in the area of glycobiotechnology/biocatalysis regarding the topics: - Combinatorial biocatalysis/enzyme cascades for the synthesis of glycoconjugates (The Golgi Glycan Factory) - Biofunctionalization of biomaterials with glycoconjugates as biomolecular recognition structures for lectins (The Glyco-BioInterface).

Lothar Elling studied Biology and received his Doctor degree (1988) from RWTH Aachen University under the supervision of Professor Dr. H. Zahn. With a post-doctoral fellowship of the German Ministry for Education and Research, he joined the Institute for Enzyme Technology of the Heinrich-Heine-University Düsseldorf in the Research Center Jülich, in 1988, working with Professor Dr. Dr. h.c. Maria-Regina Kula. In 1990, he became research associate heading the research group “Enzymes in Oligosaccharide Synthesis” at the same institute. In 1997, he finished his “Habilitation” and received the venia legendi for Enzyme Technology. Since October 2001, he is a Professor at RWTH Aachen University.

 

Selected publications:

Gottschalk, J.; Elling, L., Current state on the enzymatic synthesis of glycosaminoglycans. Curr. Opin. Chem. Biol. 2021, 61, 71-80.
Gottschalk, J.; Aßmann, M.; Kuballa, J.; Elling, L., Repetitive Synthesis of High-Molecular-Weight Hyaluronic Acid with Immobilized Enzyme Cascades. ChemSusChem 2021, 14, https://doi.org/10.1002/cssc.202101071
Heinzler, R.; Fischöder, T.; Elling, L.; Franzreb, M., Toward Automated Enzymatic Glycan Synthesis in a Compartmented Flow Microreactor System. Adv. Synth. Catal. 2019, 361, 4506-4516.
Heine, V.; Boesveld, S.; Pelantová, H.; Křen, V.; Trautwein, C.; Strnad, P.; Elling, L., Identifying Efficient Clostridium difficile Toxin A Binders with a Multivalent Neo-Glycoprotein Glycan Library. Bioconj. Chem. 2019, 30, 2373-2383.

 

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The Project is carried out within the International Research Agendas PLUS programme of the Foundation for Polish Science, co-financed by The European Union under the European Regional Development Found,with the budget of: PLN 31 000 000.

 

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