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Engineering of complex protein sialylation in plants.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America . 8/23/2016, Vol. 113 Issue 34, p9498-9503. 6p. 4 Graphs. - Publication Year :
- 2016
-
Abstract
- Sialic acids (Sias) are abundant terminal modifications of proteinlinked 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 α2,6- or α2,3-linkage were generated. Moreover, by the transient coexpression of human α2,8-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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *SIALIC acids
*AMINO compounds
*GLYCANS
*MONOSACCHARIDES
*POLYSIALIC acid
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 113
- Issue :
- 34
- Database :
- Academic Search Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 117664781
- Full Text :
- https://doi.org/10.1073/pnas.1604371113