Properties of the thioesterase component obtained by limited trypsinization of the fatty acid synthetase multienzyme complex.

Lin, Chu Yuan; Smith, Stuart

doi:10.1016/s0021-9258(19)62341-0

Cited by 110 publications

(21 citation statements)

References 32 publications

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“…Acyl-CoA hydrolase (thioesterase) activities have been reported in various mammalian tissues and in microorganisms. These enzymes are involved in a variety of biochemical processes including: regulation of intracellular fatty acid and acyl-CoA concentrations (22); hydrolysis of fatty acids from acyl-carrier protein (23); dehalogenation of chlorinated aromatic compounds in bacteria (24); bioluminescence (25); biosynthesis of polyketides (26); and cleavage of the acyl group from palmitoyl-protein including H-Ras and certain GTP binding proteins (27). As a group, these enzymes vary greatly in molecular weight, cellular location, and substrate specificity.…”

Section: Discussionmentioning

confidence: 99%

The bile acid-inducible baiF gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A hydrolase

Mallonee

Wells

et al. 1999

Journal of Lipid Research

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The human intestinal Eubacterium sp. strain VPI 12708 has been shown to have a multistep biochemical pathway for bile acid 7 ␣ -dehydroxylation. A bile acid-inducible operon encoding 9 open reading frames has been cloned and sequenced from this organism. Several of the genes in this operon have been shown to catalyze specific reactions in the 7 ␣ -dehydroxylation pathway. The baiF gene from this operon was cloned, expressed in Escherichia coli, and found to encode a novel bile acid-coenzyme A (CoA) hydrolase. The subunit molecular mass of the purified bile acid-CoA hydrolase was calculated to be 47,466 daltons and the native enzyme had a relative molecular weight of 72,000. The K m and V max for cholyl-coenzyme A (CoA) hydrolysis was approximately 175 M and 374 mol/min per mg protein, respectively. The enzyme used cholyl-CoA, 3-dehydrocholyl-CoA, and chenodeoxycholyl-CoA as substrates. No hydrolytic activity was detected using acetyl-CoA, isovaleryl-CoA, palmitoyl-CoA, or phenylacetyl-CoA as substrates. Amino acid sequence database searches showed no significant similarity of bile acid-CoA hydrolase to other thioesterases, but significant amino acid sequence identity was found with Escherichia coli carnitine dehydratase. The characteristic thioesterase active site Gly-X-Ser-X-Gly motif was not found in the amino acid sequence of this enzyme. Bile acid-CoA hydrolase from Eubacterium sp. strain VPI 12708 may represent a new family of thioesterases.-Ye, H-Q., D. H. Mallonee, J. E. Wells, I. Björkem, and P. B. Hylemon. The bile acid-inducible baiF gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A hydrolase.

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Section: Discussionmentioning

confidence: 99%

The bile acid-inducible baiF gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A hydrolase

Mallonee

Wells

et al. 1999

Journal of Lipid Research

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“…106 Thirdly, the chain-terminating TE has very limited ability to hydrolyze short and medium chain-length acyl thioesters. 83 Thus the specificities of the chain extension and chain termination steps complement each other perfectly to ensure that the predominant product released from the FAS is the 16 C atom fatty acid (Fig. 12).…”

Section: Chain Termination In Fassmentioning

confidence: 97%

“…81, 82 The limited proteolysis strategy had been previously exploited primarily as a tool for mapping of the domain organization of the FASs, 35,36 but had also resulted in the isolation of two individual domains, the TE and AT domains, both of which were found to be monomeric. 83,84 The discovery that the TE domain cleaved from DEBS3 was dimeric was surprising and impossible to reconcile with a head-to-tail arrangement of the DEBS subunits. As part of the same study, the authors found that a DEBS fragment containing all of module 5, when treated with dibromopropanone, yielded a cross-linked species of lower electrophoretic mobility, which they assumed to represent an interpolypeptide cross-linked dimer, as had originally been deduced for the FAS.…”

Section: Challenging the Head-to-tail Model For Modular Pkss: The Cam...mentioning

confidence: 99%

The type I fatty acid and polyketide synthases: a tale of two megasynthases

2007

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This review chronicles the synergistic growth of the fields of fatty acid and polyketide synthesis over the last century. In both animal fatty acid synthases and modular polyketide synthases, similar catalytic elements are covalently linked in the same order in megasynthases. Whereas in fatty acid synthases the basic elements of the design remain immutable, guaranteeing the faithful production of saturated fatty acids, in the modular polyketide synthases, the potential of the basic design has been exploited to the full for the elaboration of a wide range of secondary metabolites of extraordinary structural diversity.

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“…This shift occurs due to the loss of TE1 action, responsible for the tight regulation of the size of its products . Therefore, when fully functioning, the activity of TE1 is strongly correlated to the length of the acyl substrate, hitting its peak when the substrate is C 16 and being lower for chains longer than C 18 or shorter than C 16 . − …”

Section: The Catalytic Mechanism Of Animal Fasmentioning

confidence: 99%

Animal Fatty Acid Synthase: A Chemical Nanofactory

et al. 2021

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Fatty acids are crucial molecules for most living beings, very well spread and conserved across species. These molecules play a role in energy storage, cell membrane architecture, and cell signaling, the latter through their derivative metabolites. De novo synthesis of fatty acids is a complex chemical process that can be achieved either by a metabolic pathway built by a sequence of individual enzymes, such as in most bacteria, or by a single, large multi-enzyme, which incorporates all the chemical capabilities of the metabolic pathway, such as in animals and fungi, and in some bacteria. Here we focus on the multi-enzymes, specifically in the animal fatty acid synthase (FAS). We start by providing a historical overview of this vast field of research. We follow by describing the extraordinary architecture of animal FAS, a homodimeric multi-enzyme with seven different active sites per dimer, including a carrier protein that carries the intermediates from one active site to the next. We then delve into this multi-enzyme’s detailed chemistry and critically discuss the current knowledge on the chemical mechanism of each of the steps necessary to synthesize a single fatty acid molecule with atomic detail. In line with this, we discuss the potential and achieved FAS applications in biotechnology, as biosynthetic machines, and compare them with their homologous polyketide synthases, which are also finding wide applications in the same field. Finally, we discuss some open questions on the architecture of FAS, such as their peculiar substrate-shuttling arm, and describe possible reasons for the emergence of large megasynthases during evolution, questions that have fascinated biochemists from long ago but are still far from answered and understood.

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Properties of the thioesterase component obtained by limited trypsinization of the fatty acid synthetase multienzyme complex.

Cited by 110 publications

References 32 publications

The bile acid-inducible baiF gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A hydrolase

The bile acid-inducible baiF gene from Eubacterium sp. strain VPI 12708 encodes a bile acid-coenzyme A hydrolase

The type I fatty acid and polyketide synthases: a tale of two megasynthases

Animal Fatty Acid Synthase: A Chemical Nanofactory

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