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. This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Fatty Acids and Lipids Biosynthesis → Fatty Acid Biosynthesis|
Some taxa known to possess this pathway include : Arabidopsis thaliana col , Bacillus subtilis subtilis 168 , Brassica napus , Escherichia coli K-12 substr. MG1655 , Spinacia oleracea , Streptococcus pneumoniae [Heath00a], Vibrio albensis [MassengoTiasse08]
This pathway shows the reactions that constitute one turn of a cycle that lengthens the chain of an acyl-[acyl-carrier protein] 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 are drawn off to become components of fatty acid-containing compounds, such as phospholipids, lipid A, and lipoproteins. They comprise saturated fatty acids such as laurate (dodecanoate), myristate (tetradecanoate), palmitate (hexadecanoate), and stearate (octadecanoate).
In Escherichia coli, 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 in Escherichia coli by three enzymes, FabB, FabF, and FabH. However, FabH initiates fatty-acid synthesis: it uses only acetyl-[acp] as a substrate, and is thus not included in this pathway (see Pathway superpathway of fatty acid biosynthesis initiation (E. coli)) [Lai03]. Other organisms may use other initiation enzymes, such as FabY.
Bacteria such as Escherichia coli also contain unsaturated fatty acids. These are formed by a pathway that branches at the level of the 10-carbon intermediate (see cis-dodecenoyl biosynthesis) [Cronan03, Magnuson93]. FabB, but not FabF, participates in the synthesis of unsaturated fatty acids [Campbell01]. The activity of FabF, and hence the fraction of fatty acids that are saturated, is modultated by temperature. However, the distribution of the flow of synthesis that proceeds to saturated vs. unsaturated fatty acids is determined mostly by the activities of FabA and FabZ [Heath96].
The final step of the cycle, the reductase, is known to be catalzed by enzymes that utilize either NADH, or NADPH, or both [Bergler96]. The Escherichia coli FabI can use both cofactors, although the activity with NADH was shown to be over 17-fold higher than with NADPH [Bergler96]. FabV and FabK are NADH-specific. FabV enzymes are common in Gram-negative bacteria, and have been described from multiple organisms, including Pseudomonas aeruginosa PAO1 [Zhu10a], Burkholderia mallei [Lu10a], Xanthomonas oryzae [Li11d], Aliivibrio fischeri [Park12a], and Yersinia pestis [Hirschbeck12]. FabK enzymes are found only in some Gram-positive bacteria such as Streptococcus pneumoniae [Heath00a, Marrakchi03] and Porphyromonas gingivalis [Hevener12]. Another isoform, FabL, which is found in Bacillus subtilis and some other Gram-positive bacteria, uses only NADPH [Heath00].
Superpathways: superpathway of fatty acid biosynthesis I (E. coli)
Unification Links: EcoCyc:FASYN-ELONG-PWY
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
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
Hevener12: Hevener KE, Mehboob S, Boci T, Truong K, Santarsiero BD, Johnson ME (2012). "Expression, purification and characterization of enoyl-ACP reductase II, FabK, from Porphyromonas gingivalis." Protein Expr Purif 85(1);100-108. PMID: 22820244
Hirschbeck12: Hirschbeck MW, Kuper J, Lu H, Liu N, Neckles C, Shah S, Wagner S, Sotriffer CA, Tonge PJ, Kisker C (2012). "Structure of the Yersinia pestis FabV enoyl-ACP reductase and its interaction with two 2-pyridone inhibitors." Structure 20(1);89-100. PMID: 22244758
Li11d: Li H, Zhang X, Bi L, He J, Jiang T (2011). "Determination of the crystal structure and active residues of FabV, the enoyl-ACP reductase from Xanthomonas oryzae." PLoS One 6(10);e26743. PMID: 22039545
Marrakchi03: Marrakchi H, Dewolf WE, Quinn C, West J, Polizzi BJ, So CY, Holmes DJ, Reed SL, Heath RJ, Payne DJ, Rock CO, Wallis NG (2003). "Characterization of Streptococcus pneumoniae enoyl-(acyl-carrier protein) reductase (FabK)." Biochem J 370(Pt 3);1055-62. PMID: 12487627
Park12a: Park AK, Lee JH, Chi YM, Moon JH (2012). "Crystallization and preliminary X-ray crystallographic studies of a new class of enoyl-(acyl-carrier protein) reductase, FabV, from Vibrio fischeri." Acta Crystallogr Sect F Struct Biol Cryst Commun 68(Pt 1);78-80. PMID: 22232178
Zhu10a: Zhu L, Lin J, Ma J, Cronan JE, Wang H (2010). "Triclosan resistance of Pseudomonas aeruginosa PAO1 is due to FabV, a triclosan-resistant enoyl-acyl carrier protein reductase." Antimicrob Agents Chemother 54(2);689-98. PMID: 19933806
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
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
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
CamposGarcia98: Campos-Garcia J, Caro AD, Najera R, Miller-Maier RM, Al-Tahhan RA, Soberon-Chavez G (1998). "The Pseudomonas aeruginosa rhlG gene encodes an NADPH-dependent beta-ketoacyl reductase which is specifically involved in rhamnolipid synthesis." J Bacteriol 180(17);4442-51. PMID: 9721281
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
Caughey82: Caughey I, Kekwick RG (1982). "The characteristics of some components of the fatty acid synthetase system in the plastids from the mesocarp of avocado (Persea americana) fruit." Eur J Biochem 123(3);553-61. PMID: 7075600
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
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 263(10);4641-6. PMID: 2832401
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
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