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Gewählte Publikation:

Castilho, A; Pabst, M; Leonard, R; Veit, C; Altmann, F; Mach, L; Glössl, J; Strasser, R; Steinkellner, H.
(2008): Construction of a functional CMP-sialic acid biosynthesis pathway in Arabidopsis.
Plant Physiol. 2008; 147(1):331-339 FullText FullText_BOKU

Previous studies have reported that plants contain negligible amounts of free or protein-bound N-acetylneuraminic acid (Neu5Ac). This is a major disadvantage for the use of plants as a biopharmaceutical expression system, since N-glycans with terminal Neu5Ac residues are important for the biological activities and half-lives of recombinant therapeutic glycoproteins in humans. For the synthesis of Neu5Ac-containing N-glycans, plants have to acquire the ability to synthesize Neu5Ac and its nucleotide-activated derivative, cytidine monophospho-N-acetylneuraminic acid. In this study, we have generated transgenic Arabidopsis (Arabidopsis thaliana) plants expressing three key enzymes of the mammalian Neu5Ac biosynthesis pathway: UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, N-acetylneuraminic acid phosphate synthase, and CMP-N-acetylneuraminic acid synthetase. Simultaneous expression of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase and N-acetylneuraminic acid phosphate synthase resulted in the generation of significant Neu5Ac amounts (1,275 nmol g(-1) fresh weight in leaves) in planta, which could be further converted to cytidine monophospho-N-acetylneuraminic acid (2.4 nmol g(-1) fresh weight in leaves) by coexpression of CMP-N-acetylneuraminic acid synthetase. These findings are a major step toward the production of Neu5Ac-containing glycoproteins in plants.
Autor*innen der BOKU Wien:
Altmann Friedrich
De Vitoria Pereira Alexandra
Glößl Josef
Leonard Renaud
Mach Lukas
Pabst Martin
Steinkellner Herta
Strasser Richard
Veit Christiane
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Find related publications in this database (using NML MeSH Indexing)
Animals -
Arabidopsis - enzymology
Carbohydrate Epimerases - metabolism
Cytidine Monophosphate N-Acetylneuraminic Acid - metabolism
Humans -
Mice -
N-Acetylneuraminic Acid - biosynthesis
N-Acylneuraminate Cytidylyltransferase - metabolism
Oxo-Acid-Lyases - metabolism
Plants, Genetically Modified - enzymology
Polysaccharides - metabolism

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