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Escherichia coli K-12 substr. MG1655 Pathway: CDP-diacylglycerol biosynthesis II

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

Locations of Mapped Genes:

Superclasses: Biosynthesis Fatty Acids and Lipids Biosynthesis Phospholipid Biosynthesis CDP-diacylglycerol Biosynthesis

Summary:
General Background

Phospholipids are important components of the inner and outer membranes of E. coli. Most phospholipids are phosphoglycerides. The simplest phosphoglycerides, which are known as a 1,2-diacyl-sn-glycerol 3-phosphate (a phosphatidate), are composed of a glycerol molecule attached to two fatty acids and one phosphate group. The carboxyl group of each fatty acid is esterified to the hydroxyl groups on C-1 and C-2 of the glycerol molecule, while the phosphate group is attached to C-3 by an ester link.

Most of the fatty acids of E. coli are contained in phospholipids. The three main phospholipids of E. coli are phosphatidylethanolamine, phosphatidylglycerol and cardiolipin. Phosphatidylethanolamine comprises about 75% of the total phospholipid, with the latter two varying as to growth phase. Trace amounts of other phospholipids including monoacylphosphatidylglycerol and phosphatidylserine are also present.

The fatty acid composition of E. coli phospholipids consists of palmitate, myristate, palmitoleate, and cis-vaccenate, with trace amounts of laurate, stearate, and cis-7-tetradecenoate. The proportions depend upon both growth phase and temperature. The proportion of unsaturated fatty acids rises with decreasing temperature, which is thought to maintain membrane fluidity.

Following the synthesis of the fatty acid components of phospholipids (see pathways under class Fatty Acid Biosynthesis), they are transferred to a phosphorylated glycerol molecule (sn-glycerol 3-phosphate). The resulting 1,2-diacyl-sn-glycerol-3-phosphate is then converted to its activated derivative a CDP-diacylglycerol. Following activation, it can then be modified to form other phsophoglycerides as shown in the pathway links.

About This Pathway

This pathway describes the biosynthesis of a CDP-diacylglycerol utilizing the PlsB and PlsC enzymes. It is found in some Gram-negative bacteria, primarily the Gammaproteobacteria, including E. coli. When cells are grown on carbon sources other than glycerol, the first step of phospholipid biosynthesis is the NADH-dependent reduction of dihydroxyacetone phosphate (a glycolytic intermediate) to sn-glycerol-3-phosphate (G3P) catalyzed by glycerol-3-phosphate dehydrogenase, biosynthetic, the product of gene gpsA. The enzyme is feedback-regulated by G3P which maintains a constant intracellular concentration of this metabolite [Clark80a]. When cells are grown on glycerol, glycerol kinase can produce G3P.

The production of the intermediate 1-acyl-sn-glycerol-3-phosphate is catalyzed by membrane-bound PlsB (glycerol-3-phosphate acyltransferase) using an acyl-[acp] as the acyl donor. It transfers fatty acids (in the form of their acyl-[acp] products of fatty acid biosynthesis) to position 1 of G3P. PlsB enzymes can also utilize long-chain acyl-CoA thioesters as acyl donors (see pathway CDP-diacylglycerol biosynthesis I).

The addition of the second fatty acid acyl moiety at position 2 of G3P is catalyzed by PlsC (1-acylglycerol-3-phosphate O-acyltransferase), producing a 1,2-diacyl-sn-glycerol-3-phosphate (a phosphatidate, phosphatidic acid). This enzyme is universally expressed in all bacteria. As in the case of PlsB, it can utilize either an acyl-[acp] or a long-chain acyl-CoA thioester as the acyl donor.

The PlsB/PlsC system thus intercepts the acyl-[acp] products of the fatty acid elongation cycle and transfers the acyl chains from the acyl-[acp] to either the C-1 or C-2 position of G3P, producing 1,2-diacyl-sn-glycerol-3-phosphate, the universal phospholipid precursor in bacteria. These enzymes are therefore key regulators of fatty acid and phospholipid synthesis.

The 1,2-diacyl-sn-glycerol-3-phosphate formed by PlsC is then converted to its activated form a CDP-diacylglycerol. This compound is an intermediate in the biosynthesis of all membrane phospholipids (as indicated in the pathway links and superpathway phospholipid biosynthesis I).

It should be noted that most bacteria utilize a different route for the synthesis of 1-acyl-sn-glycerol-3-phosphate that involves genes plsX and plsY, as described in MetaCyc pathway CDP-diacylglycerol biosynthesis III [Lu06]. Although E. coli retains genes plsX and plsY (ygiH), plsB is used to synthesize 1-acyl-sn-glycerol-3-phosphate [Yoshimura07].

Reviews: [Parsons13], and Cronan, J.E. Jr., and C.O. Rock (2008) "Biosynthesis of Membrane Lipids" EcoSal 3.6.4 [ECOSAL]

Superpathways: phospholipid biosynthesis I

Variants: CDP-diacylglycerol biosynthesis I

Credits:
Created 07-Dec-2007 by Keseler I , SRI International
Revised 29-Jul-2008 by Caspi R , SRI International
Last-Curated ? 06-Jun-2013 by Fulcher C , SRI International


References

Clark80a: Clark D, Lightner V, Edgar R, Modrich P, Cronan JE, Bell RM (1980). "Regulation of phospholipid biosynthesis in Escherichia coli. Cloning of the structural gene for the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 255(2);714-7. PMID: 6985897

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Lu06: Lu YJ, Zhang YM, Grimes KD, Qi J, Lee RE, Rock CO (2006). "Acyl-phosphates initiate membrane phospholipid synthesis in Gram-positive pathogens." Mol Cell 23(5);765-72. PMID: 16949372

Parsons13: Parsons JB, Rock CO (2013). "Bacterial lipids: Metabolism and membrane homeostasis." Prog Lipid Res 52(3);249-76. PMID: 23500459

Yoshimura07: Yoshimura M, Oshima T, Ogasawara N (2007). "Involvement of the YneS/YgiH and PlsX proteins in phospholipid biosynthesis in both Bacillus subtilis and Escherichia coli." BMC Microbiol 7(1);69. PMID: 17645809

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

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

Bayan89: Bayan N, Therisod H (1989). "Evidence for interactions of acyl carrier protein with glycerol-3-phosphate acyltransferase, an inner membrane protein of Escherichia coli." FEBS Lett 1989;255(2);330-4. PMID: 2676605

Bell74: Bell RM (1974). "Mutants of Escherichia coli defective in membrane phospholipid synthesis: macromolecular synthesis in an sn-glycerol 3-phosphate acyltransferase Km mutant." J Bacteriol 117(3);1065-76. PMID: 4591941

Bell75: Bell RM, Cronan JE (1975). "Mutants of Escherichia coli defective in membrane phospholipid synthesis. Phenotypic suppression of sn-glycerol-3-phosphate acyltransferase Km mutants by loss of feedback inhibition of the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 250(18);7153-8. PMID: 240817

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

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

Byers07: Byers DM, Gong H (2007). "Acyl carrier protein: structure-function relationships in a conserved multifunctional protein family." Biochem Cell Biol 85(6);649-62. PMID: 18059524

Carter68: Carter JR (1968). "Cytidine triphosphate: phosphatidic acid cytidyltransferase in Escherichia coli." J Lipid Res 9(6);748-54. PMID: 4879388

Chang67: Chang YY, Kennedy EP (1967). "Pathways for the synthesis of glycerophosphatides in Escherichia coli." J Biol Chem 242(3);516-9. PMID: 5336962

Coleman90: Coleman J (1990). "Characterization of Escherichia coli cells deficient in 1-acyl-sn-glycerol-3- phosphate acyltransferase activity." J Biol Chem 1990;265(28);17215-21. PMID: 2211622

Coleman92a: Coleman J (1992). "Characterization of the Escherichia coli gene for 1-acyl-sn-glycerol-3-phosphate acyltransferase (plsC)." Mol Gen Genet 1992;232(2);295-303. PMID: 1557036

Cooper87: Cooper CL, Jackowski S, Rock CO (1987). "Fatty acid metabolism in sn-glycerol-3-phosphate acyltransferase (plsB) mutants." J Bacteriol 169(2);605-11. PMID: 3542964

Cronan74: Cronan JE, Bell RM (1974). "Mutants of Escherichia coli defective in membrane phospholipid synthesis: mapping of the structural gene for L-glycerol 3-phosphate dehydrogenase." J Bacteriol 118(2);598-605. PMID: 4597451

Daley05: Daley DO, Rapp M, Granseth E, Melen K, Drew D, von Heijne G (2005). "Global topology analysis of the Escherichia coli inner membrane proteome." Science 308(5726);1321-3. PMID: 15919996

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

Dowhan97: Dowhan W (1997). "CDP-diacylglycerol synthase of microorganisms." Biochim Biophys Acta 1348(1-2);157-65. PMID: 9370328

Edgar78: Edgar JR, Bell RM (1978). "Biosynthesis in Escherichia coli fo sn-glycerol 3-phosphate, a precursor of phospholipid." J Biol Chem 1978;253(18);6348-53. PMID: 355254

Edgar78a: Edgar JR, Bell RM (1978). "Biosynthesis in Escherichia coli of sn-glycerol 3-phosphate, a precursor of phospholipid. Kinetic characterization of wild type and feedback-resistant forms of the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 253(18);6354-63. PMID: 28326

Edgar79: Edgar JR, Bell RM (1979). "Biosynthesis in Escherichia coli of sn-glycerol 3-phosphate, a precursor of phospholipid. Palmitoyl-CoA inhibition of the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 1979;254(4);1016-21. PMID: 368067

Edgar80: Edgar JR, Bell RM (1980). "Biosynthesis in Escherichia coli of sn-glycerol-3-phosphate, a precursor of phospholipid. Further kinetic characterization of wild type and feedback-resistant forms of the biosynthetic sn-glycerol-3-phosphate dehydrogenase." J Biol Chem 255(8);3492-7. PMID: 6767719

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Mon Nov 24, 2014, BIOCYC14B.