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BIOCHEMICAL PROCESSES AND MACROMOLECULAR STRUCTURES

Construction of a Functional CMP-Sialic Acid Biosynthesis Pathway in Arabidopsis^1,[OA]

Institute of Applied Genetics and Cell Biology (A.C., C.V., L.M., J.G., R.S., H.S.) and Department of Chemistry (M.P., R.L., F.A.), University of Natural Resources and Applied Life Sciences, BOKU-Vienna, A–1190 Vienna, Austria

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.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantphysiol.org) is: Richard Strasser (richard.strasser{at}boku.ac.at).

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www.plantphysiol.org/cgi/doi/10.1104/pp.108.117572

^* Corresponding author; e-mail richard.strasser{at}boku.ac.at.

Received February 7, 2008; accepted March 3, 2008; published March 7, 2008.

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On the Inside

Peter V. Minorsky
Plant Physiol. 2008 147: 1-2. [Full Text]