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MetaCyc Pathway: Lipid A-core biosynthesis

Pathway diagram: Lipid A-core 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.

Superclasses: Biosynthesis Fatty Acid and Lipid Biosynthesis

Some taxa known to possess this pathway include ? : Escherichia coli K-12 substr. MG1655

Expected Taxonomic Range: Proteobacteria

Summary:
General Background

Bacterial lipopolysaccharides (LPS) typically consist of a hydrophobic domain inserted into the outer membrane known as lipid A (or endotoxin), a phosphorylated "core" oligosaccharide and a distal polysaccharide (or O antigen). The core oligosaccharides are conceptually divided into two regions: inner core and outer core. The inner core is highly conserved, comprises three deoxy-D-manno-octulosonic acid (KDO) and L-glycero-D-manno-heptose (Hep) and is often phosphorylated. The inner core oligosaccharide plays a critical role in essential barrier function of the outer membrane. The outer core comprises a tri-hexose backbone modified with varying side-branch substitutions of hexose and acetamidohexose residues. The outer core provides an attachment site for O-antigen. Strains of Escherichia coli K12 normally do not make O-antigen, unless a mutation in the O-antigen operon is corrected [Stevenson94].

About This Pathway

The completed lipid A-KDO2 serves as the acceptor on which the core oligosaccharide chains are assembled by sequential glycosyl transfer from nucleotide sugar precursors. This process involves a co-ordinated complex of membrane-associated glycosyltransferases acting at the cytoplasmic face of the plasma membrane. Many of the enzymes are predicted to be peripheral proteins.

Escherichia coli mutants that lack the heptose region of the inner core display "deep rough" phenotypes and causes instability of the outer membrane. These mutants lose expression of pili and flagella and secrete hemolysin with reduced activity. Mutations that eliminate synthesis of the outer core result in enhanced susceptibility to some hydrophobic compouns due to an indirect effect on core phosphorylation.

This topic has been reviewed in [Heinrichs98, Raetz02, Trent04, Raetz07].

Superpathways: superpathway of lipopolysaccharide biosynthesis

Unification Links: EcoCyc:LIPA-CORESYN-PWY

Credits:
Created 13-Jul-2006 by Johnson A , TIGR
Reviewed 17-Feb-2010 by Sarker M


References

Heinrichs98: Heinrichs DE, Yethon JA, Whitfield C (1998). "Molecular basis for structural diversity in the core regions of the lipopolysaccharides of Escherichia coli and Salmonella enterica." Mol Microbiol 30(2);221-32. PMID: 9791168

Raetz02: Raetz CR, Whitfield C (2002). "Lipopolysaccharide endotoxins." Annu Rev Biochem 71;635-700. PMID: 12045108

Raetz07: Raetz CR, Reynolds CM, Trent MS, Bishop RE (2007). "Lipid A modification systems in gram-negative bacteria." Annu Rev Biochem 76;295-329. PMID: 17362200

Stevenson94: Stevenson G, Neal B, Liu D, Hobbs M, Packer NH, Batley M, Redmond JW, Lindquist L, Reeves P (1994). "Structure of the O antigen of Escherichia coli K-12 and the sequence of its rfb gene cluster." J Bacteriol 1994;176(13);4144-56. PMID: 7517391

Trent04: Trent MS (2004). "Biosynthesis, transport, and modification of lipid A." Biochem Cell Biol 82(1);71-86. PMID: 15052329

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

Agladze05: Agladze K, Wang X, Romeo T (2005). "Spatial periodicity of Escherichia coli K-12 biofilm microstructure initiates during a reversible, polar attachment phase of development and requires the polysaccharide adhesin PGA." J Bacteriol 187(24);8237-46. PMID: 16321928

Austin90: Austin EA, Graves JF, Hite LA, Parker CT, Schnaitman CA (1990). "Genetic analysis of lipopolysaccharide core biosynthesis by Escherichia coli K-12: insertion mutagenesis of the rfa locus." J Bacteriol 172(9);5312-25. PMID: 2168379

Beher81: Beher MG, Schnaitman CA (1981). "Regulation of the OmpA outer membrane protein of Escherichia coli." J Bacteriol 147(3);972-85. PMID: 7024253

Brabetz97: Brabetz W, Muller-Loennies S, Holst O, Brade H (1997). "Deletion of the heptosyltransferase genes rfaC and rfaF in Escherichia coli K-12 results in an Re-type lipopolysaccharide with a high degree of 2-aminoethanol phosphate substitution." Eur J Biochem 247(2);716-24. PMID: 9266718

CarlsonBanning13: Carlson-Banning KM, Chou A, Liu Z, Hamill RJ, Song Y, Zechiedrich L (2013). "Toward repurposing ciclopirox as an antibiotic against drug-resistant Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae." PLoS One 8(7);e69646. PMID: 23936064

Chen93e: Chen L, Coleman WG (1993). "Cloning and characterization of the Escherichia coli K-12 rfa-2 (rfaC) gene, a gene required for lipopolysaccharide inner core synthesis." J Bacteriol 175(9);2534-40. PMID: 8478319

Clementz92: Clementz T (1992). "The gene coding for 3-deoxy-manno-octulosonic acid transferase and the rfaQ gene are transcribed from divergently arranged promoters in Escherichia coli." J Bacteriol 174(23);7750-6. PMID: 1447141

Coleman85: Coleman WG, Deshpande KS (1985). "New cysE-pyrE-linked rfa mutation in Escherichia coli K-12 that results in a heptoseless lipopolysaccharide." J Bacteriol 161(3);1209-14. PMID: 3882666

Creeger79: Creeger ES, Rothfield LI (1979). "Cloning of genes for bacterial glycosyltransferases. I. Selection of hybrid plasmids carrying genes for two glucosyltransferases." J Biol Chem 254(3);804-10. PMID: 368061

Czyzyk11: Czyzyk DJ, Liu C, Taylor EA (2011). "Lipopolysaccharide biosynthesis without the lipids: recognition promiscuity of Escherichia coli heptosyltransferase I." Biochemistry 50(49);10570-2. PMID: 22059588

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

Durka12: Durka M, Buffet K, Iehl J, Holler M, Nierengarten JF, Vincent SP (2012). "The inhibition of liposaccharide heptosyltransferase WaaC with multivalent glycosylated fullerenes: a new mode of glycosyltransferase inhibition." Chemistry 18(2);641-51. PMID: 22147564

Endo69: Endo A, Rothfield L (1969). "Studies of a phospholipid-requiring bacterial enzyme. I. Purification and properties of uridine diphosphate galactose: lipopolysaccharide alpha-3-galactosyl transferase." Biochemistry 8(9);3500-7. PMID: 4898284

GarciaVerdugo05: Garcia-Verdugo I, Sanchez-Barbero F, Soldau K, Tobias PS, Casals C (2005). "Interaction of SP-A (surfactant protein A) with bacterial rough lipopolysaccharide (Re-LPS), and effects of SP-A on the binding of Re-LPS to CD14 and LPS-binding protein." Biochem J 391(Pt 1);115-24. PMID: 15932345

Genevaux99: Genevaux P, Bauda P, DuBow MS, Oudega B (1999). "Identification of Tn10 insertions in the rfaG, rfaP, and galU genes involved in lipopolysaccharide core biosynthesis that affect Escherichia coli adhesion." Arch Microbiol 172(1);1-8. PMID: 10398745

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Grizot06: Grizot S, Salem M, Vongsouthi V, Durand L, Moreau F, Dohi H, Vincent S, Escaich S, Ducruix A (2006). "Structure of the Escherichia coli heptosyltransferase WaaC: binary complexes with ADP and ADP-2-deoxy-2-fluoro heptose." J Mol Biol 363(2);383-94. PMID: 16963083

Gronow00: Gronow S, Brabetz W, Brade H (2000). "Comparative functional characterization in vitro of heptosyltransferase I (WaaC) and II (WaaF) from Escherichia coli." Eur J Biochem 267(22);6602-11. PMID: 11054112

Gronow09: Gronow S, Lindner B, Brade H, Muller-Loennies S (2009). "Kdo-(2 --> 8)-Kdo-(2 --> 4)-Kdo but not Kdo-(2 --> 4)-Kdo-(2 --> 4)-Kdo is an acceptor for transfer of L-glycero-alpha-D-manno-heptose by Escherichia coli heptosyltransferase I (WaaC)." Innate Immun 15(1);13-23. PMID: 19201821

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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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