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MetaCyc Pathway: CMP-pseudaminate biosynthesis
Inferred from experiment

Enzyme View:

Pathway diagram: CMP-pseudaminate biosynthesis

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: CMP-pseudaminic acid biosynthesis

Superclasses: BiosynthesisCarbohydrates BiosynthesisSugars BiosynthesisSugar Nucleotides BiosynthesisCMP-sugar Biosynthesis

Some taxa known to possess this pathway include : Campylobacter coli, Campylobacter jejuni, Helicobacter pylori, Pseudomonas aeruginosa

Expected Taxonomic Range: Bacteria

Pseudaminic acid is a sialic acid-like sugar that was discovered in Pseudomonas aeruginosa [Knirel84]. It belongs to a class of nonulosonic acids that are unique to microorganisms and consists of 5,7-diacetamido-3,5,7,9-tetradeoxy-nonulosonate derivatives that can exhibit configurational differences compared with neuraminate [Knirel03]. Sugars that belong to this class have been found in many Gram-negative bacterial species as constituents of important cell surface glycoconjugates, such as LPS [Knirel03], capsular polysaccharide [Kiss01], pili [Castric01], and flagella [Thibault01, Schirm03]. These modifications are expected to influence pathogenesis through bacterial adhesion, invasion, and immune evasion [Hsu06].

Helicobacter pylori, which is known as a causative agent of gastric and duodenal ulcers, heavily modifies its flagellin with 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-α-L-manno-nonulosonate [Schirm03]. Flagellin glycosylation is a necessary modification allowing flagellar assembly, bacterial motility, colonization, and as a result, virulence [Josenhans02, Schirm05].

Several genes involved in this process have been discovered in Campylobacter jejuni and Helicobacter pylori, and mutations in these genes completely abolished flagellar assembly and cell motility [Josenhans02, Schirm03, Chou05] . A six step pathway from UDP-N-acetyl-α-D-glucosamine to 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-α-L-manno-nonulosonate was ultimately proposed for Helicobacter pylori [Ishiyama06], and all six enzymes catalyzing it have been identified and characterized, although not all of them to the same level [Creuzenet00, Schoenhofen06a, Schoenhofen06b, Ishiyama06, Schoenhofen06]. When all of the purified enzymes were combined in a single reaction vessel, they were able to catalyze the total conversion of UDP-N-acetyl-α-D-glucosamine to CMP-pseudaminate. However, since CMP-pseudaminate apparently inhibits some of the earlier enzymes of the pathway, optimal conversion was achieved when the process was divided into two reactions, the first one consisting of the first five enzymes, and the second one consisting of pseudaminic acid cytidylyltransferase alone [Schoenhofen06].

Created 25-Feb-2009 by Caspi R, SRI International


Castric01: Castric P, Cassels FJ, Carlson RW (2001). "Structural characterization of the Pseudomonas aeruginosa 1244 pilin glycan." J Biol Chem 276(28);26479-85. PMID: 11342554

Chou05: Chou WK, Dick S, Wakarchuk WW, Tanner ME (2005). "Identification and characterization of NeuB3 from Campylobacter jejuni as a pseudaminic acid synthase." J Biol Chem 280(43);35922-8. PMID: 16120604

Creuzenet00: Creuzenet C, Schur MJ, Li J, Wakarchuk WW, Lam JS (2000). "FlaA1, a new bifunctional UDP-GlcNAc C6 Dehydratase/ C4 reductase from Helicobacter pylori." J Biol Chem 275(45);34873-80. PMID: 10954725

Hsu06: Hsu KL, Pilobello KT, Mahal LK (2006). "Analyzing the dynamic bacterial glycome with a lectin microarray approach." Nat Chem Biol 2(3);153-7. PMID: 16462751

Ishiyama06: Ishiyama N, Creuzenet C, Miller WL, Demendi M, Anderson EM, Harauz G, Lam JS, Berghuis AM (2006). "Structural studies of FlaA1 from Helicobacter pylori reveal the mechanism for inverting 4,6-dehydratase activity." J Biol Chem 281(34);24489-95. PMID: 16651261

Josenhans02: Josenhans C, Vossebein L, Friedrich S, Suerbaum S (2002). "The neuA/flmD gene cluster of Helicobacter pylori is involved in flagellar biosynthesis and flagellin glycosylation." FEMS Microbiol Lett 210(2);165-72. PMID: 12044670

Kiss01: Kiss E, Kereszt A, Barta F, Stephens S, Reuhs BL, Kondorosi A, Putnoky P (2001). "The rkp-3 gene region of Sinorhizobium meliloti Rm41 contains strain-specific genes that determine K antigen structure." Mol Plant Microbe Interact 14(12);1395-403. PMID: 11768534

Knirel03: Knirel YA, Shashkov AS, Tsvetkov YE, Jansson PE, Zahringer U (2003). "5,7-diamino-3,5,7,9-tetradeoxynon-2-ulosonic acids in bacterial glycopolymers: chemistry and biochemistry." Adv Carbohydr Chem Biochem 58;371-417. PMID: 14719362

Knirel84: Knirel YA, Vinogradov EV, L'vov VL, Kocharova NA, Shashkov AS, Dmitriev BA, Kochetkov NK (1984). "Sialic acids of a new type from the lipopolysaccharides of Pseudomonas aeruginosa and Shigella boydii." Carbohydr Res 133(2);C5-8. PMID: 6437679

Schirm03: Schirm M, Soo EC, Aubry AJ, Austin J, Thibault P, Logan SM (2003). "Structural, genetic and functional characterization of the flagellin glycosylation process in Helicobacter pylori." Mol Microbiol 48(6);1579-92. PMID: 12791140

Schirm05: Schirm M, Schoenhofen IC, Logan SM, Waldron KC, Thibault P (2005). "Identification of unusual bacterial glycosylation by tandem mass spectrometry analyses of intact proteins." Anal Chem 77(23);7774-82. PMID: 16316188

Schoenhofen06: Schoenhofen IC, McNally DJ, Brisson JR, Logan SM (2006). "Elucidation of the CMP-pseudaminic acid pathway in Helicobacter pylori: synthesis from UDP-N-acetylglucosamine by a single enzymatic reaction." Glycobiology 16(9);8C-14C. PMID: 16751642

Schoenhofen06a: Schoenhofen IC, McNally DJ, Vinogradov E, Whitfield D, Young NM, Dick S, Wakarchuk WW, Brisson JR, Logan SM (2006). "Functional characterization of dehydratase/aminotransferase pairs from Helicobacter and Campylobacter: enzymes distinguishing the pseudaminic acid and bacillosamine biosynthetic pathways." J Biol Chem 281(2);723-32. PMID: 16286454

Schoenhofen06b: Schoenhofen IC, Lunin VV, Julien JP, Li Y, Ajamian E, Matte A, Cygler M, Brisson JR, Aubry A, Logan SM, Bhatia S, Wakarchuk WW, Young NM (2006). "Structural and functional characterization of PseC, an aminotransferase involved in the biosynthesis of pseudaminic acid, an essential flagellar modification in Helicobacter pylori." J Biol Chem 281(13);8907-16. PMID: 16421095

Thibault01: Thibault P, Logan SM, Kelly JF, Brisson JR, Ewing CP, Trust TJ, Guerry P (2001). "Identification of the carbohydrate moieties and glycosylation motifs in Campylobacter jejuni flagellin." J Biol Chem 276(37);34862-70. PMID: 11461915

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

Kneidinger03: Kneidinger B, O'Riordan K, Li J, Brisson JR, Lee JC, Lam JS (2003). "Three highly conserved proteins catalyze the conversion of UDP-N-acetyl-D-glucosamine to precursors for the biosynthesis of O antigen in Pseudomonas aeruginosa O11 and capsule in Staphylococcus aureus type 5. Implications for the UDP-N-acetyl-L-fucosamine biosynthetic pathway." J Biol Chem 278(6);3615-27. PMID: 12464616

Kneidinger03a: Kneidinger B, Larocque S, Brisson JR, Cadotte N, Lam JS (2003). "Biosynthesis of 2-acetamido-2,6-dideoxy-L-hexoses in bacteria follows a pattern distinct from those of the pathways of 6-deoxy-L-hexoses." Biochem J 371(Pt 3);989-95. PMID: 12575896

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

Mulrooney05: Mulrooney EF, Poon KK, McNally DJ, Brisson JR, Lam JS (2005). "Biosynthesis of UDP-N-acetyl-L-fucosamine, a precursor to the biosynthesis of lipopolysaccharide in Pseudomonas aeruginosa serotype O11." J Biol Chem 280(20);19535-42. PMID: 15778500

Perepelov10: Perepelov AV, Liu B, Senchenkova SN, Shashkov AS, Shevelev SD, Feng L, Wang L, Knirel YA (2010). "Structure of the O-antigen and characterization of the O-antigen gene cluster of Escherichia coli O108 containing 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-D-galacto-non-2-ulosonic (8-epilegionaminic) acid." Biochemistry (Mosc) 75(1);19-24. PMID: 20331420

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216

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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
Page generated by Pathway Tools version 19.5 (software by SRI International) on Fri Apr 29, 2016, biocyc14.