Fatty acid synthase type

Phosphopantetheine tethering is a posttranslational modification that takes place on the active site serine of carrier proteins - acyl carrier proteins (ACPs) and peptidyl carrier proteins (PCPs), also termed thiolation (T) domains - during the biosynthesis of fatty acids (FAs) (use ACPs) (Scheme 23), polyketides (PKs) (use ACPs) (Scheme 24), and nonribosomal peptides (NRPs) (use T domain) (Scheme 25). It is only after the covalent attachment of the 20-A Ppant arm, required for facile transfer of the various building block constituents of the molecules to be formed, that the carrier proteins can interact with the other components of the different multi-modular assembly lines (fatty acid synthases (FASs), polyketide synthases (PKSs), and nonribosomal peptide synthetases (NRPSs)) on which the compounds of interest are assembled. The structural organizations of FASs, PKSs, and NRPSs are analogous and can be divided into three broad classes the types I, II, and III systems. Even though the role of the carrier proteins is the same in all systems, their mode of action differs from one system to another. In the type I systems the carrier proteins usually only interact in cis with domains to which they are physically attached, with the exception of the PPTases and external type II thioesterase (TEII) domains that act in trans. In the type II systems the carrier proteins selectively interact... 

The elongation of the fatty acid by fatty acid synthase concludes at Cie, and the product, palmitate (16 0), is released. Unsaturated fatty acids and long-chain fatty acids can arise from palmitate in subsequent reactions. Fats are finally synthesized from activated fatty acids (acyl CoA) and glycerol 3-phosphate (see p. 170). To supply peripheral tissues, fats are packed by the hepatocytes into lipoprotein complexes of the VLDL type and released into the blood in this form (see p. 278). 

Zhu G, Li Y, Cai X, Millership JJ, Marchewka MJ, Keithly JS (2004) Expression and functional characterization of a giant Type I fatty acid synthase (CpFASl) gene from Cryptosporidium parvum. Mol Biochem Parasitol 134 127-135 Zhu G, Marchewka M, Keithly JS (2000) Cryptosporidium parvum appears to lack a plastid genome. Microbiol-UK 146 315-321... 

Describe two different types of fatty acid synthase. Compare the basic chemical reactions that are involved. Also, compare these with the reactions of fatty acid oxidation. 

The second type of arrangement observed for sequentially related enzymes is exemplified by the Escherichia coli fatty acid synthase (see chapter 18). This synthase is a complex of most of the enzymes involved in fatty acid synthesis. The intermediates in this case are bound to the enzyme complex until synthesis is complete. 

A detailed study of amino acid sequences and mechanistic similarities in various polyketide synthase (PKS) enzymes has led to two main types being distinguished. Type I enzymes consist of one or more large multifunctional proteins that possess a distinct active site for every enzyme-catalysed step. On the other hand, Type II enzymes are multienzyme complexes that carry out a single set of repeating activities. Like fatty acid synthases, PKSs catalyse the condensation of coenzyme A esters of simple carboxylic acids. However, the variability at each step in... 

Although high-resolution structures of type I PKS modules are not available, some insights into the topological organization of modules have been obtained. Electron microscopy on the vertebrate fatty acid synthase (whose domain layout... 

Fatty acids are made in the body by a series of Claisen-type reactions catalyzed by an enzyme called a fatty acid synthase. The enzyme uses the thioesters of malonate and acetate as building blocks (see Figure 22-3 on page 1081). 

Enzyme complexes performing similar or identical tasks can vary widely between species. An excellent example is the enzyme complex, fatty acid synthase, which catalyzes the synthesis of fatty acids from acetyl-CoA and involves seven catalytic steps (Chap. 13). In E. coli and most bacteria the complex consists of seven different enzymes. In more advanced bacteria and in eukaryotic cells there are fewer types of subunit. For example, the yeast enzyme is a multienzyme complex (Mr = 2.3 x 106) with just two types of subunit (A and B) and a stoichiometry of A Bg. The subunits are multicatalytic. Subunit A (Mr = 185,000) has three catalytic activities and subunit B (Mr = 175,000) has the remaining four. The mammalian liver complex is a dimer, with each subunit... 

Watanabe CMH, Townsend CA. Initial characterisation of a type 1 fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin Bi. Chem. Biol. 2002 9 981-988. 

Child CJ, Spencer JB, Bhogal P, Shoolingin-Jordan PM. Structural similarities between 6-methylsalicylic acid synthase from Penicillium patulum and vertebrate type 1 fatty acid synthase evidence from thiol modification studies. Biochemistry 1996 35 12267-12274. 

Although the PKSs of plants have received little attention relative to those of microbial origin, the fatty acid synthases (FASs) of a wide range of plant, animal and microbial sources have been subjected to intensive study and shown to differ in their molecular structure and complexity. Thus type 1 FASs produced by animals, fimgi and yeasts are high molecular weight multienzyme complexes, in which the individual active sites may be covalently linked components of a single polypeptide chain. In the type II FASs of... 

Long-term control is mediated by changes in the rates of synthesis and degradation of the enzymes participating in fatty acid synthesis. Animals that have fasted and are then fed high-carbohydrate, low-fat diets show marked increases in their amounts of acetyl CoA carboxylase and fatty acid synthase within a few days. This type of regulation is known as... 

Additionally, Rivkin and co-workers synthesized a variety of 4-hydroxy-3-phenylquinolin-2-(l//)-ones under solvent free microwave conditions using an activated arylmalonate <06TL2395>. Reacting the desired substituted aniline with di-(2,4,6-trichlorophenyl)-2-phenyl-malonate at 250 °C with microwave irradiation for 15 min resulted in a variety of 4-hydroxy-3-phenylquinolin-2-(l//)-ones in good yields. They also demonstrated the utility of this method in the synthesis of type I fatty acid synthase inhibitors <06BMCL4620>. Kumar et al. have reported a variation of the Friedlander quinoline synthesis. They highlight the use of CeClj THjO as a reusable catalyst in the reaction of 2-... 

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