Fatty acid synthase — an example of protein evolution by gene fusion

McCarthy, Alun D.; Hardie, D. Grahame

doi:10.1016/0968-0004(84)90184-1

Cited by 95 publications

(51 citation statements)

References 27 publications

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“…The four enzyme activities necessary for the extension and the acyl carrier protein (ACP) function can reside either as domains in one or two multifunctional polypeptides or as individual entities (16). The multidomain type has been termed the eukaryotic or type I fatty acid synthase and has been isolated from the cytosol of yeast and mammals.…”

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Alteration of the specificity and regulation of fatty acid synthesis of Escherichia coli by expression of a plant medium-chain acyl-acyl carrier protein thioesterase

Voelker¹,

Davies²

1994

J Bacteriol

225

203

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The expression of a plant (Umbellularia californica) medium-chain acyl-acyl carrier protein (ACP) thioesterase (BTE) cDNA in Escherichia coli results in a very high level of extractable medium-chain-specific hydrolytic activity but causes only a minor accumulation of medium-chain fatty acids. BTE's full impact on the bacterial fatty acid synthase is apparent only after expression in a strain deficient in fatty acid degradation, in which BTE increases the total fatty acid output of the bacterial cultures fourfold. Laurate (12:0), normally a minor fatty acid component ofE. col, becomes predominant, is secreted into the medium, and can accumulate to a level comparable to the total dry weight of the bacteria. Also, large quantities of 12:1, 14:0, and 14:1 are made. At the end of exponential growth, the pathway of saturated fatty acids is almost 100o diverted by BTE to the production of free medium-chain fatty acids, starving the cells for saturated acyl-ACP substrates for lipid biosynthesis. This results in drastic changes in membrane lipid composition from predominantly 16:0 to 18:1. The continued hydrolysis of medium-chain ACPs by the BTE causes the bacterial fatty acid synthase to produce fatty acids even when membrane production has ceased in stationary phase, which shows that the fatty acid synthesis rate can be uncoupled from phospholipid biosynthesis and suggests that acyl-ACP intermediates might normally act as feedback inhibitors for fatty acid synthase. As the fatty acid synthesis is increasingly diverted to medium chains with the onset of stationary phase, the rate of C12 production increases relative to C14 production. This observation is consistent with activity of the BTE on free acyl-ACP pools, as opposed to its interaction with fatty acid synthase-bound substrates.The fatty acid biosynthesis pathway, comprising the sequential condensation of two-carbon units onto the growing fatty acyl chain, is universal. The four enzyme activities necessary for the extension and the acyl carrier protein (ACP) function can reside either as domains in one or two multifunctional polypeptides or as individual entities (16). The multidomain type has been termed the eukaryotic or type I fatty acid synthase and has been isolated from the cytosol of yeast and mammals. In contrast, in plants, Escherichia coli, and many other prokaryotes, each fatty acid synthase reaction is catalyzed by a discrete, monofunctional enzyme. In these organisms, the growing acyl chain is bound to ACP, which is itself a soluble polypeptide. This fatty acid synthase version has been termed prokaryotic, or type II. Thus, plant and prokaryotic fatty acid synthases resemble each other in structure, and the plant fatty acid synthase resides in the chloroplast (23), which is considered to be of prokaryotic origin. Therefore, the structural similarities may be due to a common ancestry of plant and prokaryotic fatty acid synthases (14,17,20). Currently, it is not known whether type II protein components exist in a dissociated state or whether they are no...

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confidence: 99%

Alteration of the specificity and regulation of fatty acid synthesis of Escherichia coli by expression of a plant medium-chain acyl-acyl carrier protein thioesterase

Voelker¹,

Davies²

1994

J Bacteriol

225

203

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“…Conspicuously, covalently connected proteins would ensure coregulation of gene expression of related functions. The covalently linked proteins can ensure stoichiometric production of the component peptides (McCarthy and Hardie 1984). Gene fusion also confers other advantages for particular proteins.…”

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confidence: 99%

“…Gene fusion also confers other advantages for particular proteins. For example, the multifunctionality of fatty acid synthase prevents dissociation at low protein concentration (McCarthy and Hardie 1984). In these ideas or experiments, the fused proteins are viewed as linked independent functional units.…”

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“…The classic examples are the fatty acid synthase gene (McCarthy and Hardie 1984) and trypotophan synthethase gene in fungi (Burns et al 1990). Other noted cases include HisA and HisF in the histidine pathway (Lang et al 2000), glutamyland prolyl-tRNA synthetase genes (Berthonneau and Mirande 2000), the young fusion gene Sp100-rs in M. musculus (Weichenhan et al 1998), and the old fused genes of ubiquitin and ribosomal proteins in diverged organisms like yeast and human (Kirschner and Stratakis 2000).…”

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A New Function Evolved from Gene Fusion

Long¹

2000

Genome Research

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“…It is catalyzed by a complex enzyme system, fattyacid synthetase (FAS), which has been classified into two types based upon whether thc cnzymes that catalyse the individual steps in the pathway and the associated acyl carrier protein reside as catalytic sub-domains on one or two multifunctional polypeptides (type I) or are located on separate polypeptide chains (typc II) (McCarthy & Hardie, 1984). A type II FAS is found in plants and many bacteria, including E. coli, where there are six successive steps in the elongation of a fatty-acid chain (Slabas & Fawcett, 1992).…”

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Crystallization of the NADP-dependent β-keto acyl carrier protein reductase from Escherichia coli

Rafferty

Fisher

Langridge

et al. 1998

Acta Crystallogr D Biol Cryst

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The NADP-dependent fl-keto acyl carrier protein reductase (BKR) from E. coli has been crystallizcd by the hanging-drop method of vapour diffusion using poly(ethylene glycol) of average molecular weight 1450. The crystals belong to the hexagonal space group P6~22 or P6s22 with unit-cell dimensions a = b = 67.8, c --355.8 ,~. Calculated values for Vm and consideration of the packing suggest that the asymmetric unit contains a dimer. BKR catalyses the first reductive step in the elongation cycle of fatty-acid biosynthesis. It shares extensive sequence homology with the enzyme which catalyzes the second reductive step in the cycle, enoyl acyl carrier protein reductase (ENR), and thus provides an opportunity to study the evolution of enzyme function in a metabolic pathway. The structure determination will permit the analysis of the molecular basis of its catalytic mechanism and substrate specificity.

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Fatty acid synthase — an example of protein evolution by gene fusion

Cited by 95 publications

References 27 publications

Alteration of the specificity and regulation of fatty acid synthesis of Escherichia coli by expression of a plant medium-chain acyl-acyl carrier protein thioesterase

Alteration of the specificity and regulation of fatty acid synthesis of Escherichia coli by expression of a plant medium-chain acyl-acyl carrier protein thioesterase

A New Function Evolved from Gene Fusion

Crystallization of the NADP-dependent β-keto acyl carrier protein reductase from Escherichia coli

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