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.
Synonyms: type I fatty acids biosynthesis
|Superclasses:||Biosynthesis → Fatty Acid and Lipid Biosynthesis → Fatty Acid Biosynthesis|
Some taxa known to possess this pathway include : Saccharomyces cerevisiae
Expected Taxonomic Range: Fungi
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 [Zhang03c, 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].
About This Pathway
The yeast fatty acid synthase was the first type I enzyme to have been investigated [Lynen61]. The enzyme was found to be a very large complex that catalyzes the same reactions that were described for the many enzymes catalyzing fatty acids biosynthesis in bacterial systems. Initially it was believed to be an aggregate of seven distinct subunits [Sumper69, Lynen72], but eventually it was shown the the complex is made of only two types of different multifunctional subunits [Schweizer77], arranged in an α6β6 structure. The two genes encoding the subunits were cloned shortly after [Schweizer84].
The α subunit, encoded by the FAS2 gene, includes the ACP region, β-ketoacyl synthase and β-ketoacyl reductase activities, and a self phosphopantetheine: protein transferase activity, that transfers the 4'-phosphopantetheine prosthetic group from CoA to the enzyme [Fichtlscherer00]. The β subunit, encoded by FAS1, contains the remaining activities of the synthase. Among these activities is an enzyme that transfers palmitate from a palmitoyl-[acp] to CoA, generating the major product of the complex, palmitoyl-CoA.
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
Fichtlscherer00: Fichtlscherer F, Wellein C, Mittag M, Schweizer E (2000). "A novel function of yeast fatty acid synthase. Subunit alpha is capable of self-pantetheinylation." Eur J Biochem 267(9);2666-71. PMID: 10785388
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
Schweizer84: Schweizer M, Lebert C, Holtke J, Roberts LM, Schweizer E (1984). "Molecular cloning of the yeast fatty acid synthetase genes, FAS1 and FAS2: illustrating the structure of the FAS1 cluster gene by transcript mapping and transformation studies." Mol Gen Genet 194(3);457-65. PMID: 6330502
Zhang03c: 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
Chirala87: Chirala SS, Kuziora MA, Spector DM, Wakil SJ (1987). "Complementation of mutations and nucleotide sequence of FAS1 gene encoding beta subunit of yeast fatty acid synthase." J Biol Chem 262(9);4231-40. PMID: 3031066
Mohamed88: Mohamed AH, Chirala SS, Mody NH, Huang WY, Wakil SJ (1988). "Primary structure of the multifunctional alpha subunit protein of yeast fatty acid synthase derived from FAS2 gene sequence." J Biol Chem 263(25);12315-25. PMID: 2900835
Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216
Schweizer86: Schweizer M, Roberts LM, Holtke HJ, Takabayashi K, Hollerer E, Hoffmann B, Muller G, Kottig H, Schweizer E (1986). "The pentafunctional FAS1 gene of yeast: its nucleotide sequence and order of the catalytic domains." Mol Gen Genet 203(3);479-86. PMID: 3528750
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