MetaCyc Pathway: superpathway of fatty acids biosynthesis (E. coli)

Pathway diagram: superpathway of fatty acids biosynthesis (E. coli)

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

Superclasses: Biosynthesis Fatty Acid and Lipid Biosynthesis Fatty Acid Biosynthesis

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

Expected Taxonomic Range: Bacteria

This superpathway starts with the initiation of fatty acids biosynthesis by generating an acetoacetyl-[acp] from acetyl-CoA, hydrogen carbonate and a holo-[acyl-carrier protein] protein. The product, acetoacetyl-[acp], feeds into the pathway of fatty acids elongation, which involves repetition of the same four enzymatic reactions. Each repetition constitutes one turn of a cycle that lengthens the chain of an acyl-[acp] molecule by two carbons. The products of multiple turns of this cycle are drawn off to become components of fatty acid-containing compounds such as phospholipids, lipid A, and lipoproteins. Such products include the saturated fatty acids laurate, myristate, and palmitate [Marr62].

E. coli also contains unsaturated fatty acids, namely palmitoleate and cis-vaccenate. These are formed by a pathway that branches off at the level of the 10-carbon intermediate [Cronan03, Magnuson93]. Once the 10-carbon unsaturated acyl-[acp] is formed, it is elongated by the same cycle.

Of the four reactions involved in the cycle of fatty-acid elongation, two are catalyzed by more that one enzyme. These function preferentially on substrates of different chain length. They also act differentially on saturated and unsaturated substrates [Heath96]. The first reaction in the sequence, the condensation reaction, is catalyzed by three enzymes, FabB, FabF, and FabH. FabH initiates fatty-acid synthesis: it uses only acetyl-ACP as a substrate (see Pathway: fatty acid biosynthesis initiation I) [Lai03]. Only FabB catalyzes the extension of a cis3-decenoyl-[acp] to a palmitoleoyl-[acp], and only FabF can catalyze the elongation of the later to cis-vaccenate [Campbell01]. The activity of FabF and hence the fraction of fatty acids that are unsaturated is modultated by temperature [Marr62]. Thus the distribution of the flow of synthesis that proceeds to saturated vs. unsaturated fatty acids is determined by the activities of FabA, FabB and growth temperature [Heath96].

Subpathways: fatty acid biosynthesis initiation I , palmitate biosynthesis II (bacteria and plants) , cis-dodecenoate biosynthesis , palmitoleate biosynthesis I (E. coli) , cis-vaccenate biosynthesis

Created 25-Jun-2009 by Caspi R , SRI International


Campbell01: Campbell JW, Cronan JE (2001). "Escherichia coli FadR positively regulates transcription of the fabB fatty acid biosynthetic gene." J Bacteriol 183(20);5982-90. PMID: 11566998

Cronan03: Cronan JE (2003). "Bacterial membrane lipids: where do we stand?." Annu Rev Microbiol 57;203-24. PMID: 14527277

Heath96: Heath RJ, Rock CO (1996). "Roles of the FabA and FabZ beta-hydroxyacyl-acyl carrier protein dehydratases in Escherichia coli fatty acid biosynthesis." J Biol Chem 1996;271(44);27795-801. PMID: 8910376

Lai03: Lai CY, Cronan JE (2003). "Beta-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis." J Biol Chem 278(51);51494-503. PMID: 14523010

Magnuson93: Magnuson K, Jackowski S, Rock CO, Cronan JE (1993). "Regulation of fatty acid biosynthesis in Escherichia coli." Microbiol Rev 1993;57(3);522-42. PMID: 8246839

Marr62: Marr AG, Ingraham JL (1962). "Effect of temperature on the composition of fatty acids in Escherichia coli." J Bacteriol 84(6);1260-7. PMID: 16561982

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

AbdelHamid07: Abdel-Hamid AM, Cronan JE (2007). "Coordinate expression of the acetyl coenzyme A carboxylase genes, accB and accC, is necessary for normal regulation of biotin synthesis in Escherichia coli." J Bacteriol 189(2);369-76. PMID: 17056747

Alhamadsheh07: Alhamadsheh MM, Musayev F, Komissarov AA, Sachdeva S, Wright HT, Scarsdale N, Florova G, Reynolds KA (2007). "Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes." Chem Biol 14(5);513-24. PMID: 17524982

Alhamadsheh08: Alhamadsheh MM, Waters NC, Sachdeva S, Lee P, Reynolds KA (2008). "Synthesis and biological evaluation of novel sulfonyl-naphthalene-1,4-diols as FabH inhibitors." Bioorg Med Chem Lett 18(24);6402-5. PMID: 18996691

Annand93: Annand RR, Kozlowski JF, Davisson V J, Schwab JM (1993). "Mechanism-based inactivation of Escherichia coli .beta.-hydroxydecanoyl thiol ester dehydrase: assignment of the imidazole nitrogen-15 NMR resonances and determination of the structure of the alkylated histidine." Journal of the American Chemical Society 115(3);1088-1094.

Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

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

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

Barber05: Barber MC, Price NT, Travers MT (2005). "Structure and regulation of acetyl-CoA carboxylase genes of metazoa." Biochim Biophys Acta 1733(1);1-28. PMID: 15749055

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

Benson08: Benson BK, Meades G, Grove A, Waldrop GL (2008). "DNA inhibits catalysis by the carboxyltransferase subunit of acetyl-CoA carboxylase: implications for active site communication." Protein Sci 17(1);34-42. PMID: 18156466

Berg07: Berg IA, Kockelkorn D, Buckel W, Fuchs G (2007). "A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea." Science 318(5857);1782-6. PMID: 18079405

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

Bilder06: Bilder P, Lightle S, Bainbridge G, Ohren J, Finzel B, Sun F, Holley S, Al-Kassim L, Spessard C, Melnick M, Newcomer M, Waldrop GL (2006). "The structure of the carboxyltransferase component of acetyl-coA carboxylase reveals a zinc-binding motif unique to the bacterial enzyme." Biochemistry 45(6);1712-22. PMID: 16460018

Blanchard98: Blanchard CZ, Waldrop GL (1998). "Overexpression and kinetic characterization of the carboxyltransferase component of acetyl-CoA carboxylase." J Biol Chem 273(30);19140-5. PMID: 9668099

Blanchard99: Blanchard CZ, Chapman-Smith A, Wallace JC, Waldrop GL (1999). "The biotin domain peptide from the biotin carboxyl carrier protein of Escherichia coli acetyl-CoA carboxylase causes a marked increase in the catalytic efficiency of biotin carboxylase and carboxyltransferase relative to free biotin." J Biol Chem 1999;274(45);31767-9. PMID: 10542197

Bognar87: Bognar AL, Osborne C, Shane B (1987). "Primary structure of the Escherichia coli folC gene and its folylpolyglutamate synthetase-dihydrofolate synthetase product and regulation of expression by an upstream gene." J Biol Chem 262(25);12337-43. PMID: 3040739

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

Borgaro11: Borgaro JG, Chang A, Machutta CA, Zhang X, Tonge PJ (2011). "Substrate recognition by β-ketoacyl-ACP synthases." Biochemistry 50(49);10678-86. PMID: 22017312

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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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