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Escherichia coli K-12 substr. MG1655 Pathway: UDP-N-acetyl-D-glucosamine biosynthesis I

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Synonyms: UDP-N-acetyl-D-glucosamine biosynthesis

Superclasses: Biosynthesis Amines and Polyamines Biosynthesis UDP-N-acetyl-D-glucosamine Biosynthesis
Biosynthesis Cell Structures Biosynthesis Lipopolysaccharide Biosynthesis O-Antigen Biosynthesis

Summary:
UDP-N-acetyl-α-D-glucosamine (UDP-GlcNAc) is an essential precursor of cell wall peptidoglycan, lipopolysaccharide and enterobacterial common antigen. This situates UDP-GlcNAc at a branch point in metabolism, each fork leading to synthesis of a major envelope component of the cell [Neidhardt96]. The enzymes of these pathways are targets for development of novel antibacterial compounds (reviewed in [Kotnik07]).

L-glutamine:D-fructose-6-phosphate aminotransferase, or GFAT, catalyzes the first committed step in UDP-GlcNAc biosynthesis from fructose-6-phosphate. The product of this first reaction, D-glucosamine 6-phosphate, can also be transported into the cell and utilized as a source of carbon; thus, expression of GFAT is controlled at several levels. For details on regulation and the mechanism of uncoupling it from the regulation of glmU expression, please see the protein page: L-glutamine:D-fructose-6-phosphate aminotransferase.

D-glucosamine 6-phosphate is then converted to D-glucosamine 1-phosphate by phosphoglucosamine mutase. The two final reactions of the pathway, transfer of an acetyl group from acetyl-CoA to form N-acetyl-α-D-glucosamine 1-phosphate and transfer of a uridyl group to form the final product, UDP-GlcNAc, are carried out by a bifunctional enzyme, GlmU, which contains two domains that carry out each reaction independently.

Review: [Barreteau08]

Superpathways: O-antigen building blocks biosynthesis (E. coli)

Credits:
Last-Curated ? 04-Oct-2007 by Keseler I , SRI International


References

Barreteau08: Barreteau H, Kovac A, Boniface A, Sova M, Gobec S, Blanot D (2008). "Cytoplasmic steps of peptidoglycan biosynthesis." FEMS Microbiol Rev 32(2);168-207. PMID: 18266853

Kotnik07: Kotnik M, Anderluh PS, Prezelj A (2007). "Development of novel inhibitors targeting intracellular steps of peptidoglycan biosynthesis." Curr Pharm Des 13(22);2283-309. PMID: 17692001

Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.

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

Ahn11: Ahn J, Chung BK, Lee DY, Park M, Karimi IA, Jung JK, Lee H (2011). "NADPH-dependent pgi-gene knockout Escherichia coli metabolism producing shikimate on different carbon sources." FEMS Microbiol Lett 324(1);10-6. PMID: 22092758

Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Badet87: Badet B, Vermoote P, Haumont PY, Lederer F, LeGoffic F (1987). "Glucosamine synthetase from Escherichia coli: purification, properties, and glutamine-utilizing site location." Biochemistry 1987;26(7);1940-8. PMID: 3297136

Badet88: Badet B, Vermoote P, Le Goffic F (1988). "Glucosamine synthetase from Escherichia coli: kinetic mechanism and inhibition by N3-fumaroyl-L-2,3-diaminopropionic derivatives." Biochemistry 1988;27(7);2282-7. PMID: 3132968

BadetDenisot92: Badet-Denisot MA, Badet B (1992). "Chemical modification of glucosamine-6-phosphate synthase by diethyl pyrocarbonate: evidence of histidine requirement for enzymatic activity." Arch Biochem Biophys 1992;292(2);475-8. PMID: 1731613

BadetDenisot95: Badet-Denisot MA, Leriche C, Massiere F, Badet B (1995). "Nitrogen transfer in E. coli glucosamine-6P synthase. Investigations using substrate and bisubstrate analogs." Bioorg. Med. Chem. Lett. 5(8);815-820.

Bearne00: Bearne SL, Blouin C (2000). "Inhibition of Escherichia coli glucosamine-6-phosphate synthase by reactive intermediate analogues. The role of the 2-amino function in catalysis." J Biol Chem 275(1);135-40. PMID: 10617596

Bearne95: Bearne SL, Wolfenden R (1995). "Glutamate gamma-semialdehyde as a natural transition state analogue inhibitor of Escherichia coli glucosamine-6-phosphate synthase." Biochemistry 34(36);11515-20. PMID: 7547881

Bearne96: Bearne SL (1996). "Active site-directed inactivation of Escherichia coli glucosamine-6-phosphate synthase. Determination of the fructose 6-phosphate binding constant using a carbohydrate-based inactivator." J Biol Chem 271(6);3052-7. PMID: 8621700

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Brown99a: Brown K, Pompeo F, Dixon S, Mengin-Lecreulx D, Cambillau C, Bourne Y (1999). "Crystal structure of the bifunctional N-acetylglucosamine 1-phosphate uridyltransferase from Escherichia coli: a paradigm for the related pyrophosphorylase superfamily." EMBO J 18(15);4096-107. PMID: 10428949

Burton06: Burton E, Gawande PV, Yakandawala N, LoVetri K, Zhanel GG, Romeo T, Friesen AD, Madhyastha S (2006). "Antibiofilm activity of GlmU enzyme inhibitors against catheter-associated uropathogens." Antimicrob Agents Chemother 50(5);1835-40. PMID: 16641457

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Byrne14: Byrne RT, Chen SH, Wood EA, Cabot EL, Cox MM (2014). "Surviving extreme exposure to ionizing radiation: Escherichia coli genes and pathways." J Bacteriol. PMID: 25049088

Canonaco01: Canonaco F, Hess TA, Heri S, Wang T, Szyperski T, Sauer U (2001). "Metabolic flux response to phosphoglucose isomerase knock-out in Escherichia coli and impact of overexpression of the soluble transhydrogenase UdhA." FEMS Microbiol Lett 204(2);247-52. PMID: 11731130

Charusanti10: Charusanti P, Conrad TM, Knight EM, Venkataraman K, Fong NL, Xie B, Gao Y, Palsson BO (2010). "Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene." PLoS Genet 6(11);e1001186. PMID: 21079674

Chmara84: Chmara H, Zahner H (1984). "The inactivation of glucosamine synthetase from bacteria by anticapsin, the C-terminal epoxyamino acid of the antibiotic tetaine." Biochim Biophys Acta 787(1);45-52. PMID: 6426523

Chmara85: Chmara H (1985). "Inhibition of glucosamine synthase by bacilysin and anticapsin." J Gen Microbiol 131(2);265-71. PMID: 3884731

Csonka77: Csonka LN, Fraenkel DG (1977). "Pathways of NADPH formation in Escherichia coli." J Biol Chem 252(10);3382-91. PMID: 16899

De96a: De Luca C, Lansing M, Crescenzi F, Martini I, Shen GJ, O'Regan M, Wong CH (1996). "Overexpression, one-step purification and characterization of UDP-glucose dehydrogenase and UDP-N-acetylglucosamine pyrophosphorylase." Bioorg Med Chem 4(1);131-41. PMID: 8689233

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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