Reconstitution in vitro of the GDP-fucose biosynthetic pathways of Caenorhabditis elegans and Drosophila melanogaster

The FEBS Journal
Simone RhombergIain B H Wilson

Abstract

The deoxyhexose sugar fucose has an important fine-tuning role in regulating the functions of glycoconjugates in disease and development in mammals. The two genetic model organisms Caenorhabditis elegans and Drosophila melanogaster also express a range of fucosylated glycans, and the nematode particularly has a number of novel forms. For the synthesis of such glycans, the formation of GDP-fucose, which is generated from GDP-mannose in three steps catalysed by two enzymes, is required. By homology we have identified and cloned cDNAs encoding these two proteins, GDP-mannose dehydratase (GMD; EC 4.2.1.47) and GDP-keto-6-deoxymannose 3,5-epimerase/4-reductase (GER or FX protein; EC 1.1.1.271), from both Caenorhabditis and Drosophila. Whereas the nematode has two genes encoding forms of GMD (gmd-1 and gmd-2) and one GER-encoding gene (ger-1), the insect has, like mammalian species, only one homologue of each (gmd and gmer). This compares to the presence of two forms of both enzymes in Arabidopsis thaliana. All corresponding cDNAs from Caenorhabditis and Drosophila, as well as the previously uncharacterized Arabidopsis GER2, were separately expressed, and the encoded proteins found to have the predicted activity. The biochemical char...Continue Reading

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Citations

Aug 30, 2008·Glycoconjugate Journal·Katharina PaschingerIain B H Wilson
Apr 26, 2013·The Journal of Biological Chemistry·Sílvia SanzLuis Izquierdo
Jun 1, 2014·Proceedings of the National Academy of Sciences of the United States of America·Therese WohlschlagerMarkus Künzler
Dec 29, 2009·Biochemical and Biophysical Research Communications·Yan RenWei Chen
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Mar 28, 2019·Frontiers in Molecular Biosciences·Katharina PaschingerIain B H Wilson
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Sep 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chien-Sen LiaoChien-Chang Wu
Dec 2, 2008·The Biochemical Journal·Martin GutterniggIain B H Wilson

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