Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of ‘native’ helminth N-glycan structures in planta

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Abstract

Secretory glycoproteins of parasitic helminths are in the spotlight as biopharmaceuticals because of their strong, glycan-dependent immunomodulatory properties. Helminths and their secretions have been shown to dampen allergic reactions and autoimmune disorders, such as inflammatory bowel diseases, multiple sclerosis and rheumatoid arthritis. Clinical trials with live parasites and mouse model studies with excretory/secretory proteins are promising and reveal an urgent need for the large-scale production of defined secretory glycoproteins from helminths. Helminth N-glycans contribute to immunomodulation, but have unique structures that cannot be synthesized in current biopharmaceutical production systems. The trematode Schistosoma mansoni produces complex highly fucosylated N-glycan structures on its glycoproteins. Therefore, modifications of the N-glycosylation machinery of the expression host are required for the production of S. mansoni--derived immunomodulatory glycoproteins with their native N-glycans. This can be achieved by knocking-in or knocking-out specific glycosyltransferases, allowing synthesis of specific helminth N-glycan structures. Plants are remarkable versatile as glyco-engineering platform for the synthesis of glycoproteins with tailored N-glycans. However, for the synthesis of highly fucosylated N-glycans from S. mansoni knowledge is lacking on how these specific structures are synthesized. For this purpose, we examined the function of ten selected fucosyltransferases from Schistosoma mansoni using transient co-expression with immunomodulatory omega-1 as a model protein. Two fucosyltransferases were identified that specifically couple fucoses to the core glucosamine with an α1,3 or α1,6 bond. These two fucosyltransferases can be used to obtain α1,3- and α1,6 core fucosylated N-glycan structures found on native helminth secreted immunomodulatory proteins. Our results show the versatility of plants both as a production system and as a system for characterizing glycosyltransferase functionality. Further characterization of S. mansoni fucosyltransferases and other glycosyltransferases will expand our glyco-engineering toolbox and offers perspectives for the synthesis of novel complex helminth N-glycan structures in plants.
Original languageEnglish
Publication statusPublished - May 2016
EventThe second conference of the International Society for Plant Molecular Farming - Ghent, Belgium
Duration: 25 May 201627 May 2016
http://www.societyformolecularfarming.org/

Conference

ConferenceThe second conference of the International Society for Plant Molecular Farming
CountryBelgium
CityGhent
Period25/05/1627/05/16
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van Noort, K., Wilbers, R. H. P., Westerhof, L. B., & Schots, A. (2016). Characterization of Schistosoma mansoni fucosyltransferases for glyco-engineering of ‘native’ helminth N-glycan structures in planta. Abstract from The second conference of the International Society for Plant Molecular Farming, Ghent, Belgium.