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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

Abstract:
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
Glößl Josef
Leonard Renaud
Mach Lukas
Machado Ferreira Castilho Alexandra
Pabst Martin
Steinkellner Herta
Strasser Richard
Veit Christiane
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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