University of Natural Resources and Life Sciences, Vienna (BOKU) - Research portal
Selected Publication:
Kallolimath, S; Castilho, A; Strasser, R; Grunwald-Gruber, C; Altmann, F; Strubl, S; Galuska, CE; Zlatina, K; Galuska, SP; Werner, S; Thiesler, H; Werneburg, S; Hildebrandt, H; Gerardy-Schahn, R; Steinkellner, H.
(2016):
Engineering of complex protein sialylation in plants
P NATL ACAD SCI USA. 2016; 113(34): 9498-9503.
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- Abstract:
- Sialic acids (Sias) are abundant terminal modifications of protein-linked glycans. A unique feature of Sia, compared with other monosaccharides, is the formation of linear homo-polymers, with its most complex form polysialic acid (polySia). Sia and polySia mediate diverse biological functions and have great potential for therapeutic use. However, technological hurdles in producing defined protein sialylation due to the enormous structural diversity render their precise investigation a challenge. Here, we describe a plant-based expression platform that enables the controlled in vivo synthesis of sialylated structures with different interlinkages and degree of polymerization (DP). The approach relies on a combination of stably transformed plants with transient expression modules. By the introduction of multigene vectors carrying the human sialylation pathway into glycosylation-destructed mutants, transgenic plants that sialylate glycoproteins in alpha 2,6-or alpha 2,3-linkage were generated. Moreover, by the transient coexpression of human alpha 2,8-polysialyltransferases, polySia structures with a DP >40 were synthesized in these plants. Importantly, plant-derived polySia are functionally active, as demonstrated by a cell-based cytotoxicity assay and inhibition of microglia activation. This pathway engineering approach enables experimental investigations of defined sialylation and facilitates a rational design of glycan structures with optimized biotechnological functions.
- Authors BOKU Wien:
- Altmann Friedrich
- Grünwald-Gruber Clemens
- Kallolimath Somanath
- Machado Ferreira Castilho Alexandra
- Steinkellner Herta
- Strasser Richard
- Find related publications in this database (Keywords)
- protein polysialylation
- Nicotiana benthamiana
- recombinant proteins
- glycoengineering
- in planta sialylation
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