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Escherichia coli K-12 substr. MG1655 Pathway: superpathway of (KDO)2-lipid A biosynthesis

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

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Biosynthesis Cell Structures Biosynthesis Lipopolysaccharide Biosynthesis
Biosynthesis Fatty Acids and Lipids Biosynthesis
Superpathways

Summary:
Lipid A is the hydrophobic anchor of the outer membrane lipopolysaccharide. Free lipid A does not exist as such in cells. It is normally found glycosylated with two KDO (3-deoxy-D-manno-octulosonic acid) residues and acylated with laurate and myristate residues.

However if cells are subjected to cold shock or grown at low temperatures the laurate residue is replaced by palmitoleate. Myristate is subsequently added, resulting in a distinct cold adapted form of KDO2-lipid A. [Neidhardt96, Clementz96, Brozek90, Clementz97, Carty99]

A PagP homodimer can catalyze palmitate transfer from a phospholipid (sn-1 position) to lipid A or to a lipid A precursor (N-linked hydroxymyristate on the proximal unit) [Bishop00]. The catalytic site localizes to the exterior of the outer membrane, indicating that enzyme activity may require outer membrane problems that result in mislocalization of palmitate-donor phospholipids from the interior face to the exterior face of the outer membrane [Hwang02a].

Subpathways: KDO transfer to lipid IVA I , lipid IVA biosynthesis , CMP-KDO biosynthesis I


References

Bishop00: Bishop RE, Gibbons HS, Guina T, Trent MS, Miller SI, Raetz CR (2000). "Transfer of palmitate from phospholipids to lipid A in outer membranes of gram-negative bacteria." EMBO J 19(19);5071-80. PMID: 11013210

Brozek90: Brozek KA, Raetz CR (1990). "Biosynthesis of lipid A in Escherichia coli. Acyl carrier protein-dependent incorporation of laurate and myristate." J Biol Chem 1990;265(26);15410-7. PMID: 2203778

Carty99: Carty SM, Sreekumar KR, Raetz CR (1999). "Effect of cold shock on lipid A biosynthesis in Escherichia coli. Induction At 12 degrees C of an acyltransferase specific for palmitoleoyl-acyl carrier protein." J Biol Chem 1999;274(14);9677-85. PMID: 10092655

Clementz96: Clementz T, Bednarski JJ, Raetz CR (1996). "Function of the htrB high temperature requirement gene of Escherchia coli in the acylation of lipid A: HtrB catalyzed incorporation of laurate." J Biol Chem 1996;271(20);12095-102. PMID: 8662613

Clementz97: Clementz T, Zhou Z, Raetz CR (1997). "Function of the Escherichia coli msbB gene, a multicopy suppressor of htrB knockouts, in the acylation of lipid A. Acylation by MsbB follows laurate incorporation by HtrB." J Biol Chem 1997;272(16);10353-60. PMID: 9099672

Hwang02a: Hwang PM, Choy WY, Lo EI, Chen L, Forman-Kay JD, Raetz CR, Prive GG, Bishop RE, Kay LE (2002). "Solution structure and dynamics of the outer membrane enzyme PagP by NMR." Proc Natl Acad Sci U S A 99(21);13560-5. PMID: 12357033

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

Airoldi10: Airoldi C, Sommaruga S, Merlo S, Sperandeo P, Cipolla L, Polissi A, Nicotra F (2010). "Targeting bacterial membranes: NMR spectroscopy characterization of substrate recognition and binding requirements of D-arabinose-5-phosphate isomerase." Chemistry 16(6);1897-902. PMID: 20039350

Anderson85a: Anderson MS, Bulawa CE, Raetz CR (1985). "The biosynthesis of gram-negative endotoxin. Formation of lipid A precursors from UDP-GlcNAc in extracts of Escherichia coli." J Biol Chem 1985;260(29);15536-41. PMID: 3905795

Anderson87: Anderson MS, Raetz CR (1987). "Biosynthesis of lipid A precursors in Escherichia coli. A cytoplasmic acyltransferase that converts UDP-N-acetylglucosamine to UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine." J Biol Chem 262(11);5159-69. PMID: 3549716

Anderson88c: Anderson MS, Robertson AD, Macher I, Raetz CR (1988). "Biosynthesis of lipid A in Escherichia coli: identification of UDP-3-O-[(R)-3-hydroxymyristoyl]-alpha-D-glucosamine as a precursor of UDP-N2,O3-bis[(R)-3-hydroxymyristoyl]-alpha-D-glucosamine." Biochemistry 1988;27(6);1908-17. PMID: 3288280

Anderson92: Anderson MS, Raetz CR (1992). "UDP-N-acetylglucosamine 3-O-acyltransferase from Escherichia coli." Methods Enzymol 1992;209;449-54. PMID: 1495425

Anderson93: Anderson MS, Bull HG, Galloway SM, Kelly TM, Mohan S, Radika K, Raetz CR (1993). "UDP-N-acetylglucosamine acyltransferase of Escherichia coli. The first step of endotoxin biosynthesis is thermodynamically unfavorable." J Biol Chem 1993;268(26);19858-65. PMID: 8366124

Asojo01: Asojo O, Friedman J, Adir N, Belakhov V, Shoham Y, Baasov T (2001). "Crystal structures of KDOP synthase in its binary complexes with the substrate phosphoenolpyruvate and with a mechanism-based inhibitor." Biochemistry 40(21);6326-34. PMID: 11371194

Baasov93: Baasov T, Sheffer-Dee-Noor S, Kohen A, Jakob A, Belakhov V (1993). "Catalytic mechanism of 3-deoxy-D-manno-2-octulosonate-8-phosphate synthase. The use of synthetic analogues to probe the structure of the putative reaction intermediate." Eur J Biochem 217(3);991-9. PMID: 8223657

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Babinski02: Babinski KJ, Ribeiro AA, Raetz CR (2002). "The Escherichia coli gene encoding the UDP-2,3-diacylglucosamine pyrophosphatase of lipid A biosynthesis." J Biol Chem 277(29);25937-46. PMID: 12000770

Babinski02a: Babinski KJ, Kanjilal SJ, Raetz CR (2002). "Accumulation of the lipid A precursor UDP-2,3-diacylglucosamine in an Escherichia coli mutant lacking the lpxH gene." J Biol Chem 277(29);25947-56. PMID: 12000771

Badger05: Badger J, Sauder JM, Adams JM, Antonysamy S, Bain K, Bergseid MG, Buchanan SG, Buchanan MD, Batiyenko Y, Christopher JA, Emtage S, Eroshkina A, Feil I, Furlong EB, Gajiwala KS, Gao X, He D, Hendle J, Huber A, Hoda K, Kearins P, Kissinger C, Laubert B, Lewis HA, Lin J, Loomis K, Lorimer D, Louie G, Maletic M, Marsh CD, Miller I, Molinari J, Muller-Dieckmann HJ, Newman JM, Noland BW, Pagarigan B, Park F, Peat TS, Post KW, Radojicic S, Ramos A, Romero R, Rutter ME, Sanderson WE, Schwinn KD, Tresser J, Winhoven J, Wright TA, Wu L, Xu J, Harris TJ (2005). "Structural analysis of a set of proteins resulting from a bacterial genomics project." Proteins 60(4);787-96. PMID: 16021622

Barb08: Barb AW, Zhou P (2008). "Mechanism and inhibition of LpxC: an essential zinc-dependent deacetylase of bacterial lipid A synthesis." Curr Pharm Biotechnol 9(1);9-15. PMID: 18289052

Bartling08: Bartling CM, Raetz CR (2008). "Steady-state kinetics and mechanism of LpxD, the N-acyltransferase of lipid A biosynthesis." Biochemistry 47(19);5290-302. PMID: 18422345

Bartling09: Bartling CM, Raetz CR (2009). "Crystal structure and acyl chain selectivity of Escherichia coli LpxD, the N-acyltransferase of lipid A biosynthesis." Biochemistry 48(36);8672-83. PMID: 19655786

Bateman99: Bateman A (1999). "The SIS domain: a phosphosugar-binding domain." Trends Biochem Sci 24(3);94-5. PMID: 10203754

Beall87: Beall B, Lutkenhaus J (1987). "Sequence analysis, transcriptional organization, and insertional mutagenesis of the envA gene of Escherichia coli." J Bacteriol 169(12);5408-15. PMID: 2824434

Belunis92: Belunis CJ, Raetz CR (1992). "Biosynthesis of endotoxins. Purification and catalytic properties of 3-deoxy-D-manno-octulosonic acid transferase from Escherichia coli." J Biol Chem 1992;267(14);9988-97. PMID: 1577828

Belunis95: Belunis CJ, Clementz T, Carty SM, Raetz CR (1995). "Inhibition of lipopolysaccharide biosynthesis and cell growth following inactivation of the kdtA gene in Escherichia coli." J Biol Chem 270(46);27646-52. PMID: 7499229

Bigham84: Bigham EC, Gragg CE, Hall WR, Kelsey JE, Mallory WR, Richardson DC, Benedict C, Ray PH (1984). "Inhibition of arabinose 5-phosphate isomerase. An approach to the inhibition of bacterial lipopolysaccharide biosynthesis." J Med Chem 27(6);717-26. PMID: 6429331

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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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