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Escherichia coli K-12 substr. MG1655 Pathway: cis-vaccenate biosynthesis
Inferred from experiment

Pathway diagram: cis-vaccenate biosynthesis

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

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for cis-vaccenate biosynthesis

Synonyms: cis vaccenic acid acid biosynthesis

Superclasses: BiosynthesisFatty Acid and Lipid BiosynthesisFatty Acid BiosynthesisUnsaturated Fatty Acid Biosynthesis

General Background

The only unsaturated fatty acids found in E. coli, palmitoleate and cis-vaccenate, comprise about one-half the fatty acid content of the organism [Gelmann72]. The proportion of unsaturated fatty acids is known to increase in E. coli with lower growth temperature. This phenomenon, found in most organisms, that provides a mechanism for adjusting the lipid phase transition of the membrane phospholipids to differing temperatures.

KASII encoded by fabF is the only enzyme that can catalyze the conversion of palmitoleate to cis-vaccenate, and is believed to play a major role in the thermal regulation of fatty acid composition of the membrane phospholipids of E. coli [Garwin80a]. KASII is one of three β-ketoacyl-ACP synthases (KAS) in E. coli: KASI, KASII and KASIII, encoded by fabB, fabF and fabH, respectively.

It has been shown that KASII is more active at low temperatures (relative to the overall rate of fatty acid synthesis) than at high temperatures [Garwin80]. This relative increase results in the production of cis-vaccenate rather than palmitoleate. Furthermore, because the former (but not the later) can be incorporated into both positions of sn-glycerol 3-phosphate, the synthesis of diunsaturated phospholipids occurs and the thermotrophic phase transition of the membrane phospholipids is lowered [Garwin80a].

About This Pathway

The first step in the biosynthesis of cis-vaccenate from palmitoleate is elongation from C16 to C18 with formation of a 3-oxo group, catalyzed by the product of fabF. The next three steps then complete the elongation cycle. These include reduction of the 3-oxo group, dehydration to form the trans-2-enoyl-ACP a (2-trans-11-cis)-vaccen-2-enoyl-[acp], and reduction of the resulting 2,3 double bond to form the acyl-ACP, a cis-vaccenoyl-[acp].

The dehydration step is catalyzed by FabZ. A second dehydratase encoded by fabA prefers substrates with 10-carbon aliphatic chains and does not use unsaturated substrates [Heath96, Leesong96]. FabA functions at the branch point between saturated and unsaturated fatty acid biosynthesis (see pathway (5Z)-dodec-5-enoate biosynthesis).

The identity of the reductase that catalyzes the fourth reaction is likely to be FabI. It has been suggested that FabI is probably the only such reductase that participates in both saturated and unsaturated fatty acid biosynthesis in E. coli [Heath95]. The acyl-ACP ( a cis-vaccenoyl-[acp]) formed is utilized for phospholipid biosynthesis (see pathway CDP-diacylglycerol biosynthesis II). In the final reaction, although the function of the TesA thioesterase is unclear, it can potentially liberate the free fatty acid cis-vaccenate.

Reviews: [White05], and Cronan, J.E. Jr., and C.O. Rock (2008) "Biosynthesis of Membrane Lipids" EcoSal 3.6.4 [ECOSAL]

Superpathways: superpathway of unsaturated fatty acids biosynthesis (E. coli)

Variants: (5Z)-dodec-5-enoate biosynthesis

Created 11-Jul-2008 by Caspi R, SRI International
Last-Curated 15-May-2013 by Fulcher C, SRI International


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

Garwin80: Garwin JL, Klages AL, Cronan JE (1980). "Structural, enzymatic, and genetic studies of beta-ketoacyl-acyl carrier protein synthases I and II of Escherichia coli." J Biol Chem 1980;255(24);11949-56. PMID: 7002930

Garwin80a: Garwin JL, Klages AL, Cronan JE (1980). "Beta-ketoacyl-acyl carrier protein synthase II of Escherichia coli. Evidence for function in the thermal regulation of fatty acid synthesis." J Biol Chem 1980;255(8);3263-5. PMID: 6988423

Gelmann72: Gelmann EP, Cronan JE (1972). "Mutant of Escherichia coli deficient in the synthesis of cis-vaccenic acid." J Bacteriol 112(1);381-7. PMID: 4562402

Heath95: Heath RJ, Rock CO (1995). "Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli." J Biol Chem 270(44);26538-42. PMID: 7592873

Heath96: Heath RJ, Rock CO (1996). "Regulation of fatty acid elongation and initiation by acyl-acyl carrier protein in Escherichia coli." J Biol Chem 1996;271(4);1833-6. PMID: 8567624

Leesong96: Leesong M, Henderson BS, Gillig JR, Schwab JM, Smith JL (1996). "Structure of a dehydratase-isomerase from the bacterial pathway for biosynthesis of unsaturated fatty acids: two catalytic activities in one active site." Structure 4(3);253-64. PMID: 8805534

White05: White SW, Zheng J, Zhang YM, Rock (2005). "The structural biology of type II fatty acid biosynthesis." Annu Rev Biochem 74;791-831. PMID: 15952903

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

Baldock96: Baldock C, Rafferty JB, Sedelnikova SE, Baker PJ, Stuitje AR, Slabas AR, Hawkes TR, Rice DW (1996). "A mechanism of drug action revealed by structural studies of enoyl reductase." Science 274(5295);2107-10. PMID: 8953047

Barnes68: Barnes EM, Wakil SJ (1968). "Studies on the mechanism of fatty acid synthesis. XIX. Preparation and general properties of palmityl thioesterase." J Biol Chem 1968;243(11);2955-62. PMID: 4871199

Bergler92: Bergler H, Hogenauer G, Turnowsky F (1992). "Sequences of the envM gene and of two mutated alleles in Escherichia coli." J Gen Microbiol 1992;138 ( Pt 10);2093-100. PMID: 1364817

Bergler94: Bergler H, Wallner P, Ebeling A, Leitinger B, Fuchsbichler S, Aschauer H, Kollenz G, Hogenauer G, Turnowsky F (1994). "Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli." J Biol Chem 1994;269(8);5493-6. PMID: 8119879

Bergler96: Bergler H, Fuchsbichler S, Hogenauer G, Turnowsky F (1996). "The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA." Eur J Biochem 242(3);689-94. PMID: 9022698

Bonner72: Bonner WM, Bloch K (1972). "Purification and properties of fatty acyl thioesterase I from Escherichia coli." J Biol Chem 1972;247(10);3123-33. PMID: 4554913

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

Campbell01: Campbell JW, Cronan JE (2001). "Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery." Annu Rev Microbiol 55;305-32. PMID: 11544358

Chan10a: Chan DI, Vogel HJ (2010). "Current understanding of fatty acid biosynthesis and the acyl carrier protein." Biochem J 430(1);1-19. PMID: 20662770

Chisholm60: Chisholm MJ, Hopkins C Y (1960). "11-octadecenoic acid and other fatty acids of Asclepias syriaca seed oil." Canadian Journal of Chemistry 38(6);805-812.

Chisholm65: Chisholm MJ, Hopkins C Y (1965). "Fatty acids of doxantha seed oil." Journal of the American Oil Chemists' Society 42(1);49-50.

Cho94: Cho H, Cronan JE (1994). ""Protease I" of Escherichia coli functions as a thioesterase in vivo." J Bacteriol 176(6);1793-5. PMID: 8132479

Cho95: Cho H, Cronan JE (1995). "Defective export of a periplasmic enzyme disrupts regulation of fatty acid synthesis." J Biol Chem 270(9);4216-9. PMID: 7876180

DAgnolo75: D'Agnolo G, Rosenfeld IS, Vagelos PR (1975). "Multiple forms of beta-ketoacyl-acyl carrier protein synthetase in Escherichia coli." J Biol Chem 250(14);5289-94. PMID: 237914

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

Edwards97: Edwards P, Nelsen JS, Metz JG, Dehesh K (1997). "Cloning of the fabF gene in an expression vector and in vitro characterization of recombinant fabF and fabB encoded enzymes from Escherichia coli." FEBS Lett 402(1);62-6. PMID: 9013860

Escaich11: Escaich S, Prouvensier L, Saccomani M, Durant L, Oxoby M, Gerusz V, Moreau F, Vongsouthi V, Maher K, Morrissey I, Soulama-Mouze C (2011). "The MUT056399 inhibitor of FabI is a new antistaphylococcal compound." Antimicrob Agents Chemother 55(10);4692-7. PMID: 21825292

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."

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by Pathway Tools version 19.5 (software by SRI International) on Mon May 2, 2016, biocyc14.