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Pathway Description
Fatty Acid Biosynthesis
Escherichia coli
Metabolic Pathway
The fatty acid biosynthesis starts from acetyl-CoA reacting either with a holo-[acp] through a 3-oxoacyl-[acp] synthase 3 resulting in an acetyl-[acp] or react with hydrogen carbonate through an ATP driven acetyl-CoA carboxylase resulting in a malonyl-CoA.
Malonyl-CoA reacts with a holo-acp] through a malonyl-CoA-ACP transacylase resulting in a malonyl-[acp]. This compound can react with a KASI protein resulting in an acetyl-[acp]. A malonyl-[acp] can also react with an acetyl-[acp] through KASI and KASII or with acetyl-CoA through a beta-ketoacyl-ACP synthase to produce an acetoacetyl-[acp]. An acetoacetyl-[acp] is also known as a 3-oxoacyl-[acp].
A 3-oxoacyl-[acp] is reduced through a NDPH mediated 3-oxoacyl-[acp] reductase resulting in a (3R)-3-hydroxyacyl-[acp] (R3 hydroxydecanoyl-[acp]) which can either join the fatty acid metabolism, be dehydrated by an 3R-hydroxymyristoyl-[acp] dehydratase to produce a trans-2-enoyl-[acp] or be dehydrated by a hydroxydecanoyl-[acp] to produce a trans-delta2 decenoyl-[acp].
Trans-2-enoyl-[acp] is reduced by a NADH driven enoyl-[acp] reductase resulting in a 2,3,4-saturated fatty acyl-[acp]. This product then reacts with malonyl-[acp] through KASI and KASII resulting in a holo-acyl carrier protein and a 3- oxoacyl-[acp].
Trans-delta2 decenoyl-[acp] reacts with a 3-hydroxydecanoyl-[acp] dehydrase producing a cis-delta 3-decenoyl-ACP. This product then reacts with KASI to produce a 3-oxo-cis-delta5-dodecenoyl-[acp], which in turn is reduced by a NADPH driven 3-oxoacyl-[acp] resulting in a 3R-hydroxy cis delta5-dodecenoyl-acp. This product is dehydrated by a (3R)-hydroxymyristoyl-[acp] dehydratase resulting in a trans-delta 3- cis-delta 5-dodecenoyl-[acp] which in turn is reduced by a NADH driven enoyl-[acp] reductase resulting in a cis-delta5-dodecenoyl-acp which becomes a metabolite of fatty acid metabolism
References
Fatty Acid Biosynthesis References
Bergler H, Fuchsbichler S, Hogenauer G, Turnowsky F: 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. 1996 Dec 15;242(3):689-94.
Pubmed: 9022698
Campbell JW, Cronan JE Jr: Escherichia coli FadR positively regulates transcription of the fabB fatty acid biosynthetic gene. J Bacteriol. 2001 Oct;183(20):5982-90. doi: 10.1128/JB.183.20.5982-5990.2001.
Pubmed: 11566998
Cronan JE: Bacterial membrane lipids: where do we stand? Annu Rev Microbiol. 2003;57:203-24. doi: 10.1146/annurev.micro.57.030502.090851.
Pubmed: 14527277
Heath RJ, Rock CO: Roles of the FabA and FabZ beta-hydroxyacyl-acyl carrier protein dehydratases in Escherichia coli fatty acid biosynthesis. J Biol Chem. 1996 Nov 1;271(44):27795-801.
Pubmed: 8910376
Lai CY, Cronan JE: Beta-ketoacyl-acyl carrier protein synthase III (FabH) is essential for bacterial fatty acid synthesis. J Biol Chem. 2003 Dec 19;278(51):51494-503. doi: 10.1074/jbc.M308638200. Epub 2003 Sep 30.
Pubmed: 14523010
Magnuson K, Jackowski S, Rock CO, Cronan JE Jr: Regulation of fatty acid biosynthesis in Escherichia coli. Microbiol Rev. 1993 Sep;57(3):522-42.
Pubmed: 8246839
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