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 Acid and Lipid Biosynthesis → Fatty Acid Biosynthesis|
Some taxa known to possess this pathway include : Escherichia coli K-12 substr. MG1655
Fatty acids are key building blocks for the phospholipid components of cell membranes and are determinants of intracellular communication, in the form of lipid second messengers [Prieschl00], and fatty acyl moieties of proteins that modify their location and function [Resh99].
There are two basic types of fatty acid (FAS) biosynthesis mechanisms. The type I system is found in mammals and lower eukaryotes. The mammalian system consists of a single gene product that contains all of the reaction centers required to produce a fatty acid (see fatty acid synthase from Homo sapiens), while the system of lower eukaryotes (such as yeast) consists of two genes, whose polypeptide products combine to form a multifunctional complex (see fatty acid synthase from Saccharomyces cerevisiae).
Type II systems are found in bacteria, plants [White05], parasites of the Apicomplexa phylum [Ferguson07] and mitochondria [Zhang03h, Miinalainen03]. The reactions in these systems are catalyzed by a series of individual soluble proteins that are each encoded by a discrete gene, and the pathway intermediates are transferred between the enzymes as thioesters of a holo-[acyl-carrier protein].
The best studied pathway is that of Escherichia coli K-12, from which all the enzymes have been purified and crystalized. In plants fatty acid synthesis occurs mainly in plastids of leaf mesophyll cells, seeds, and oil-accumulating fruits. Although most of the synthesis occurrs in plastids, it has been shown that mitochondria are also capable of synthesizing fatty acids [Yasuno04].
Fatty acid biosynthesis starts with an initiation sequence that produces an acetoacetyl-[acp], an activated molecule that is used for subsequent elongation reactions, which ultimately produce the final fatty acid products. This superpathway describes only the initiation sequence, subsequent elongation reactions are described in the pathways fatty acid elongation -- saturated and (5Z)-dodec-5-enoate biosynthesis.
About This Pathway
Escherichia coli K-12 has several different routes in which it can produce acetoacetyl-ACP, using different combinations of its three β-ketoacyl-ACP synthases (KAS), KASI, KASII and KASIII, which are encoded by fabB, fabF and fabH, respectively. In general, the fabH-encoded enzyme is responsible for the initiation of fatty acid elongation, utilizing acyl-coA primers, while the fabB/fabF products are responsible for the subsequent rounds of elongation, condensing malonyl-ACP with different length acyl-ACPs to extend the acyl chain by two carbons [White05, Schujman08].
Three pathways for the initiation of fatty acid biosynthesis have been proposed [Tsay92].
In the second pathway (see fatty acid biosynthesis initiation II) the acetate moiety is first transferred from acetyl-CoA to an acetyl-[acp] by acetyl-CoA:ACP transacylase (this is a second function of KASIII; it is not clear whether an additional dedicated enzyme exists in the organism). The acetyl-ACP is then condensed with a malonyl-[acp] by KASI (or alternatively KASII).
The third pathway (see fatty acid biosynthesis initiation III) involves the decarboxylation of a malonyl-[acp] by KASI to form an acetyl-[acp] followed by subsequent condensation with a second a malonyl-[acp].
It is now believed that KASIII is the key enzyme in the initiation of fatty acids biosynthesis [White05]. It selectively catalyzes the formation of acetoacetyl-ACP and specifically uses CoA thioesters rather than acyl-ACP as the primer. The products tend to be shorter than the products of KASI and II, which are involved primarily in elongation reactions, and unlike the other two enzymes, KASIII cannot participate in the terminal elongation steps of fatty acid biosynthesis.
While KASI and KASII have been shown in vitro to utilize substrates with short acyl moieties, forming acetoacetyl-ACP, the importance of these enzyme for initiation of fatty acid biosynthesis in vivo is not clear [White05].
Superpathways: superpathway of fatty acid biosynthesis I (E. coli)
Unification Links: EcoCyc:FASYN-INITIAL-PWY
Ferguson07: Ferguson DJ, Campbell SA, Henriquez FL, Phan L, Mui E, Richards TA, Muench SP, Allary M, Lu JZ, Prigge ST, Tomley F, Shirley MW, Rice DW, McLeod R, Roberts CW (2007). "Enzymes of type II fatty acid synthesis and apicoplast differentiation and division in Eimeria tenella." Int J Parasitol 37(1);33-51. PMID: 17112527
Miinalainen03: Miinalainen IJ, Chen ZJ, Torkko JM, Pirila PL, Sormunen RT, Bergmann U, Qin YM, Hiltunen JK (2003). "Characterization of 2-enoyl thioester reductase from mammals. An ortholog of YBR026p/MRF1'p of the yeast mitochondrial fatty acid synthesis type II." J Biol Chem 278(22);20154-61. PMID: 12654921
Tsay92: Tsay JT, Oh W, Larson TJ, Jackowski S, Rock CO (1992). "Isolation and characterization of the beta-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12." J Biol Chem 1992;267(10);6807-14. PMID: 1551888
Yasuno04: Yasuno R, von Wettstein-Knowles P, Wada H (2004). "Identification and molecular characterization of the beta-ketoacyl-[acyl carrier protein] synthase component of the Arabidopsis mitochondrial fatty acid synthase." J Biol Chem 279(9);8242-51. PMID: 14660674
Zhang03h: Zhang L, Joshi AK, Smith S (2003). "Cloning, expression, characterization, and interaction of two components of a human mitochondrial fatty acid synthase. Malonyltransferase and acyl carrier protein." J Biol Chem 278(41);40067-74. PMID: 12882974
AbdelHamid07a: 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
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
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
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
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
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
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
Choi00: Choi KH, Heath RJ, Rock CO (2000). "beta-ketoacyl-acyl carrier protein synthase III (FabH) is a determining factor in branched-chain fatty acid biosynthesis." J Bacteriol 182(2);365-70. PMID: 10629181
Clough92: Clough RC, Matthis AL, Barnum SR, Jaworski JG (1992). "Purification and characterization of 3-ketoacyl-acyl carrier protein synthase III from spinach. A condensing enzyme utilizing acetyl-coenzyme A to initiate fatty acid synthesis." J Biol Chem 267(29);20992-8. PMID: 1328217
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