MetaCyc Pathway: GDP-L-fucose biosynthesis I (from GDP-D-mannose)

Enzyme View:

Pathway diagram: GDP-L-fucose biosynthesis I (from GDP-D-mannose)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Synonyms: GDP-L-fucose biosynthesis I (de novo synthesis)

Superclasses: Biosynthesis Carbohydrates Biosynthesis Sugars Biosynthesis Sugar Nucleotides Biosynthesis GDP-sugar Biosynthesis

Some taxa known to possess this pathway include ? : Arabidopsis thaliana col , Escherichia coli K-12 substr. MG1655 , Homo sapiens , Mortierella alpina

Expected Taxonomic Range: Bacteria , Eukaryota

General Background

L-fucopyranose is an important monosaccharide found in a diverse array of organisms. It is a carbohydrate component of bacterial lipopolysaccharides, mammalian and plant glycoproteins (such as the human antigenic glycoproteins or glycolipids of erythrocyte membranes) and various plant cell wall polysaccharides. It is found in xyloglucans and rhamnogalacturonans I and II. Fucosylation is performed by fucosyltransferases which require the activated form GDP-L-fucose (GDP-Fuc) as the donor substrate.

The formation of GDP-L-fucose occurs via two routes: a) a de novo synthesis route from GDP-α-D-mannose (this pathway), and b) a salvage pathway leading to the formation of UDP-Fuc from free L-fucopyranose (GDP-L-fucose biosynthesis II (from L-fucose)).

Key Notes on the Enzymes:

The de novo synthesis of GDP-Fuc from GDP-D-mannose (GDP-Man) comprises three catalytic steps: a 4,6-dehydration, a 3,5-epimerization, and a 4-reduction. The first reaction step is catalyzed by GDP-mannose 4,6-dehydratase, which involved the formation of the intermediate GDP-4-dehydro-6-deoxy-α-D-mannose. In Arabidopsis thaliana, the MUR1 encodes a protein which was shown to possess this catalytic activity. In bacteria (Escherichia coli), fungi (Mortierella alpina), plants (Arabidopsis thaliana) and humans, the second and third reactions steps have been shown to be catalyzed by a single bifunctional polypeptide: GDP-fucose synthase [Nakayama03, Sullivan98, Tonetti96, Ren10]. The coexpression of Arabidopsis thaliana MUR1 and GER1 (encoding for GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase) genes in yeast cells led to the production of GDP-Fuc from GDP-Man [Nakayama03].

Superpathways: colanic acid building blocks biosynthesis , superpathway of GDP-mannose-derived O-antigen building blocks biosynthesis

Unification Links: AraCyc:PWY-66 , EcoCyc:PWY-66


Nakayama03: Nakayama K, Maeda Y, Jigami Y (2003). "Interaction of GDP-4-keto-6-deoxymannose-3,5-epimerase-4-reductase with GDP-mannose-4,6-dehydratase stabilizes the enzyme activity for formation of GDP-fucose from GDP-mannose." Glycobiology 13(10);673-80. PMID: 12881408

Ren10: Ren Y, Perepelov AV, Wang H, Zhang H, Knirel YA, Wang L, Chen W (2010). "Biochemical characterization of GDP-L-fucose de novo synthesis pathway in fungus Mortierella alpina." Biochem Biophys Res Commun 391(4);1663-9. PMID: 20035716

Sullivan98: Sullivan FX, Kumar R, Kriz R, Stahl M, Xu GY, Rouse J, Chang XJ, Boodhoo A, Potvin B, Cumming DA (1998). "Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro." J Biol Chem 273(14);8193-202. PMID: 9525924

Tonetti96: Tonetti M, Sturla L, Bisso A, Benatti U, De Flora A (1996). "Synthesis of GDP-L-fucose by the human FX protein." J Biol Chem 271(44);27274-9. PMID: 8910301

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Albermann01: Albermann C, Piepersberg W (2001). "Expression and identification of the RfbE protein from Vibrio cholerae O1 and its use for the enzymatic synthesis of GDP-D-perosamine." Glycobiology 11(8);655-61. PMID: 11479276

Albermann01a: Albermann C, Piepersberg W, Wehmeier UF (2001). "Synthesis of the milk oligosaccharide 2'-fucosyllactose using recombinant bacterial enzymes." Carbohydr Res 334(2);97-103. PMID: 11502265

Andrianopoulos98: Andrianopoulos K, Wang L, Reeves PR (1998). "Identification of the fucose synthetase gene in the colanic acid gene cluster of Escherichia coli K-12." J Bacteriol 1998;180(4);998-1001. PMID: 9473059

Bonin00: Bonin CP, Reiter WD (2000). "A bifunctional epimerase-reductase acts downstream of the MUR1 gene product and completes the de novo synthesis of GDP-L-fucose in Arabidopsis." Plant J 21(5);445-54. PMID: 10758496

Bonin97: Bonin CP, Potter I, Vanzin GF, Reiter WD (1997). "The MUR1 gene of Arabidopsis thaliana encodes an isoform of GDP-D-mannose-4,6-dehydratase, catalyzing the first step in the de novo synthesis of GDP-L-fucose." Proc Natl Acad Sci U S A 94(5);2085-90. PMID: 9050909

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014."

Byun07: Byun SG, Kim MD, Lee WH, Lee KJ, Han NS, Seo JH (2007). "Production of GDP-L-fucose, L-fucose donor for fucosyloligosaccharide synthesis, in recombinant Escherichia coli." Appl Microbiol Biotechnol 74(4);768-75. PMID: 17111133

Chen03a: Chen S, Huang X, Zhou X, Bai L, He J, Jeong KJ, Lee SY, Deng Z (2003). "Organizational and mutational analysis of a complete FR-008/candicidin gene cluster encoding a structurally related polyene complex." Chem Biol 10(11);1065-76. PMID: 14652074

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Elbein65: Elbein AD, Heath EC (1965). "The biosynthesis of cell wall lipopolysaccharide in Escherichia coli. II. Guanosine diphosphate 4-keto-6-deoxy-d-mannose, an intermediate in the biosynthesis of guanosine diphosphate colitose." J Biol Chem 240;1926-31. PMID: 14299611

Ginsburg61: Ginsburg V (1961). "Studies on the biosynthesis of guanosine diphosphate L-fucose." J Biol Chem 236;2389-93. PMID: 13705522

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Kneidinger01a: Kneidinger B, Graninger M, Adam G, Puchberger M, Kosma P, Zayni S, Messner P (2001). "Identification of two GDP-6-deoxy-D-lyxo-4-hexulose reductases synthesizing GDP-D-rhamnose in Aneurinibacillus thermoaerophilus L420-91T." J Biol Chem 276(8);5577-83. PMID: 11096116

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lau08: Lau ST, Tanner ME (2008). "Mechanism and active site residues of GDP-fucose synthase." J Am Chem Soc 130(51);17593-602. PMID: 19053199

Menon99: Menon S, Stahl M, Kumar R, Xu GY, Sullivan F (1999). "Stereochemical course and steady state mechanism of the reaction catalyzed by the GDP-fucose synthetase from Escherichia coli." J Biol Chem 274(38);26743-50. PMID: 10480878

Mulichak02: Mulichak AM, Bonin CP, Reiter WD, Garavito RM (2002). "Structure of the MUR1 GDP-mannose 4,6-dehydratase from Arabidopsis thaliana: implications for ligand binding and specificity." Biochemistry 41(52);15578-89. PMID: 12501186

Rizzi98: Rizzi M, Tonetti M, Vigevani P, Sturla L, Bisso A, Flora AD, Bordo D, Bolognesi M (1998). "GDP-4-keto-6-deoxy-D-mannose epimerase/reductase from Escherichia coli, a key enzyme in the biosynthesis of GDP-L-fucose, displays the structural characteristics of the RED protein homology superfamily." Structure 6(11);1453-65. PMID: 9817848

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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