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

van Noort, K. (Speaker)

Activity: Talk or presentationOral presentation

Description

Clinical trials with live parasites and mouse model studies have shown the potential of helminths and their excretory/secretory (ES) proteins to dampen allergic reactions and autoimmune disorders. Moreover, glycan-dependent mechanisms of action have been shown to be involved in several cases. To further develop helminth-derived ES glycoproteins as biopharmaceuticals, a large-scale expression system is required for the production of recombinant glycoproteins with defined and tailored glycosylation. The trematode Schistosoma mansoni produces highly fucosylated N-glycan structures on its glycoproteins, which cannot be synthesized in current production systems. Thereto, co-expression of specific fucosyltransferases in the expression host are required to introduce helminth-like N-glycan modifications. In the GeneDB database 20 different S. mansoni fucosyltransferase(SmFucTs) genes for N-glycosylation can be found. To date one α1,3 fucosyltransferase is characterized in vitro using glycan acceptors and shows to synthesize Lewis X. Since in vitro and in vivo characterization may differ, characterization in a biological setting, using the Golgi-system, can be more relevant. Thereto, we examined the function of ten selected SmFucTs by transient co-expression with model proteins in Nicotiana benthamiana plants. With this method we have identified SmFucTs that fucosylate LDN, synthesize Lewis X or are involved in core fucosylation. These functionally characterized fucosyltransferases can immediately be applied to synthesize desired helminth-like N-glycan structures on recombinant glycoproteins in the plant. Therefore characterization of SmFucTs, other glycosyltransferases and combinations of different glycosyltransferases expands our glyco-engineering toolbox and offers perspectives for large scale production of glycoproteins with functional helminth N-glycan structures in plants.
Period4 Sep 2017
Held atMolecular and Cellular Biology of Helminths XI
Event typeConference
LocationHydra, Greece
Degree of RecognitionInternational