Escherichia coli K-12 substr. MG1655 Pathway: fatty acid elongation -- saturated
Inferred from experiment

Pathway diagram: fatty acid elongation -- saturated

Note: a dashed line (without arrowheads) between two compound names is meant to imply that the two names are just different instantiations of the same compound -- i.e. one may be a specific name and the other a general name, or they may both represent the same compound in different stages of a polymerization-type pathway. 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 fatty acid elongation -- saturated

Superclasses: BiosynthesisFatty Acid and Lipid BiosynthesisFatty Acid Biosynthesis

This pathway shows the reactions that constitute one turn of a cycle that lengthens the chain of an acyl-ACP molecule by two carbons. The pathway is fed acetoacetyl-ACP (see Pathway superpathway of fatty acid biosynthesis initiation (E. coli)) which is a substrate of the second reaction shown here. The products of multiple turns of this cycle that are drawn off to become components of fatty acid-containing compounds such as phospholipids, lipid A, and lipoproteins are the saturated fatty acids , lauric (dodecanoic), myristic (tetradecanoic), palmitic (hexadecanoic), and stearic (octadecanoic) acids. E. coli also contains unsaturated fatty acids. These are formed by a pathway (see (5Z)-dodec-5-enoate biosynthesis) that branches at the level of the 10-carbon intermediate. [Cronan03] [Magnuson93]. The final step of the cycle, the reductase, once thought to be catalyzed by two enzymes, has been shown to be catalyzed by a single enzyme, FabI, that can use either NADH or NADPH as a cofactor. However, the activity with NADH was over 17-fold higher than with NADPH [Bergler96], thus the designation of the E. coli enzyme as EC

Of the four reactions involved in a 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 superpathway of fatty acid biosynthesis initiation (E. coli)) [Lai03]. Only FabB catalyzes one step in the synthesis of unsaturated fatty acids [Campbell01] The activity of FabF and hence the fraction of fatty acids that are unsaturated in modultated by temperature. The distribution of the flow of synthesis that proceeds to saturated vs. unsaturated fatty acids is determined by the activities of FabA and FabZ [Heath96].

Superpathways: superpathway of fatty acid biosynthesis I (E. coli)


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

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

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

Alberts72: Alberts AW, Bell RM, Vagelos PR (1972). "Acyl carrier protein. XV. Studies of -ketoacyl-acyl carrier protein synthetase." J Biol Chem 247(10);3190-8. PMID: 5027749

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.

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

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

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

Brock67: Brock DJ, Kass LR, Bloch K (1967). "Beta-hydroxydecanoyl thioester dehydrase. II. Mode of action." J Biol Chem 242(19);4432-40. PMID: 4863740

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

Campbell01a: Campbell JW, Cronan JE (2001). "Bacterial fatty acid biosynthesis: targets for antibacterial drug discovery." Annu Rev Microbiol 55;305-32. PMID: 11544358

Cao10: Cao Y, Yang J, Xian M, Xu X, Liu W (2010). "Increasing unsaturated fatty acid contents in Escherichia coli by coexpression of three different genes." Appl Microbiol Biotechnol 87(1);271-80. PMID: 20135119

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

Clark83: Clark DP, DeMendoza D, Polacco ML, Cronan JE (1983). "Beta-hydroxydecanoyl thio ester dehydrase does not catalyze a rate-limiting step in Escherichia coli unsaturated fatty acid synthesis." Biochemistry 1983;22(25);5897-902. PMID: 6362720

Cronan72: Cronan JE, Silbert DF, Wulff DL (1972). "Mapping of the fabA locus for unsaturated fatty acid biosynthesis in Escherichia coli." J Bacteriol 112(1);206-11. PMID: 4562395

Cronan73: Cronan JE, Gelmann EP (1973). "An estimate of the minimum amount of unsaturated fatty acid required for growth of Escherichia coli." J Biol Chem 248(4);1188-95. PMID: 4568811

Cronan88: Cronan JE, Li WB, Coleman R, Narasimhan M, de Mendoza D, Schwab JM (1988). "Derived amino acid sequence and identification of active site residues of Escherichia coli beta-hydroxydecanoyl thioester dehydrase." J Biol Chem 1988;263(10);4641-6. PMID: 2832401

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

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

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

Showing only 20 references. To show more, press the button "Show all references".

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 Pathway Tools version 20.0 (software by SRI International) on Fri May 6, 2016, BIOCYC13B.