On the Structure of Fatty Acid Synthetase of Yeast

Lynen, Feodor; Engeser, Hansjörg; Foerster, E C; Fox, Jeffrey L.; Heß, Stefan; Kresze, Georg-Burkhard; Schmitt, Thomas M.; Schreckenbach, Thomas; Siess, Elmar A.; Wieland, Felix; Winnewisser, W.

doi:10.1111/j.1432-1033.1980.tb06105.x

Cited by 160 publications

(62 citation statements)

References 45 publications

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“…The general term ' swinging arm ' (' Schwingarm ') was established for the yeast FAS complex in the late 1960s by Lynen (Sumper et al 1969) and was used to describe how the fatty acid reaction intermediates, which remain covalently attached to the FAS via the phosphopantetheine, are shuttled between the different active sites. However, in the late 1970s, when more structural information for the yeast FAS complex became available (see next paragraph), Lynen noted that the length of the phosphopantetheine arm (y20 Å ) would not be sufficient to overcome distances of up to 100 Å by simple rotation of the swinging arm alone, and he proposed that ' part of the protein must also be involved in this transport processes ' (Lynen, 1980). Indeed, a possible candidate, the phosphopantetheinecontaining, proteolytic 16 kDa fragment corresponding to yeast FAS ACP had been detected and analyzed earlier (Schreckenbach et al 1977 ;Willecke et al 1969).…”

Section: The Swinging Arm Hypothesismentioning

confidence: 99%

“…It became clear that the numerous individual proteins previously detected had been the result of unspecific proteolysis during the preparation. At the beginning of the 1980s, the active site peptides of several catalytic domains had been identified and the catalytic activities had been further characterized biochemically (Lynen, 1980), but the location of the catalytic residues within both multifunctional polypeptides and the approximate domain borders could only be reliably established when the primary structures of both yeast FAS subunits were published in the middle of the 1980s (Mohamed et al 1988 ;Schweizer et al 1986), which enabled further mutagenesis experiments (Fichtlscherer et al 2000;Schuster et al 1995). For the understanding of such a complex multienzyme, the knowledge of its threedimensional (3D) structure is of critical importance, and consequently structural studies on fungal FAS were pursued in parallel with its biochemical and genetic characterization.…”

Section: Structural Investigation Of Fungal Fas By Cross-linking Analmentioning

confidence: 99%

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Structure and function of eukaryotic fatty acid synthases

Maier

Leibundgut

Boehringer

et al. 2010

Quart. Rev. Biophys.

123

127

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Abstract. In all organisms, fatty acid synthesis is achieved in variations of a common cyclic reaction pathway by stepwise, iterative elongation of precursors with two-carbon extender units. In bacteria, all individual reaction steps are carried out by monofunctional dissociated enzymes, whereas in eukaryotes the fatty acid synthases (FASs) have evolved into large multifunctional enzymes that integrate the whole process of fatty acid synthesis. During the last few years, important advances in understanding the structural and functional organization of eukaryotic FASs have been made through a combination of biochemical, electron microscopic and X-ray crystallographic approaches. They have revealed the strikingly different architectures of the two distinct types of eukaryotic FASs, the fungal and the animal enzyme system. Fungal FAS is a 2Á6 MDa a 6 b 6 heterododecamer with a barrel shape enclosing two large chambers, each containing three sets of active sites separated by a central wheel-like structure. It represents a highly specialized micro-compartment strictly optimized for the production of saturated fatty acids. In contrast, the animal FAS is a 540 kDa X-shaped homodimer with two lateral reaction clefts characterized by a modular domain architecture and large extent of conformational flexibility that appears to contribute to catalytic efficiency.

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Section: The Swinging Arm Hypothesismentioning

confidence: 99%

Section: Structural Investigation Of Fungal Fas By Cross-linking Analmentioning

confidence: 99%

Structure and function of eukaryotic fatty acid synthases

Maier

Leibundgut

Boehringer

et al. 2010

Quart. Rev. Biophys.

123

127

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“…There are two types of FA synthesis (types I and II), according to the organization of the enzymes (Lynen, 1980). The enzymes in type I FA synthesis are found in the cytosol of animal and fungal cells, and all the enzymatic activities are located on one or two multifunctional polypeptide chains (Wakil, 1989).…”

Section: Kasi Is Highly Conserved In Plants and Microbesmentioning

confidence: 99%

Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development

2010

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Lipid metabolism plays a pivotal role in cell structure and in multiple plant developmental processes. b-Ketoacyl-[acyl carrier protein] synthase I (KASI) catalyzes the elongation of de novo fatty acid (FA) synthesis. Here, we report the functional characterization of KASI in the regulation of chloroplast division and embryo development. Phenotypic observation of an Arabidopsis thaliana T-DNA insertion mutant, kasI, revealed multiple morphological defects, including chlorotic (in netted patches) and curly leaves, reduced fertility, and semidwarfism. There are only one to five enlarged chloroplasts in the mesophyll cells of chlorotic sectors of young kasI rosette leaves, indicating suppressed chloroplast division under KASI deficiency. KASI deficiency results in a significant change in the polar lipid composition, which causes the suppressed expression of FtsZ and Min system genes, disordered Z-ring placement in the oversized chloroplast, and inhibited polymerization of FtsZ protein at mid-site of the chloroplast in kasI. In addition, KASI deficiency results in disrupted embryo development before the globular stage and dramatically reduces FA levels (;33.6% of the wild type) in seeds. These results demonstrate that de novo FA synthesis is crucial and has pleiotropic effects on plant growth. The polar lipid supply is important for chloroplast division and development, revealing a key function of FA synthesis in plastid development.

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“…The detailed reaction mechanisms of paradigm FASs from bacterial (112), fungal (82), plant (49,104), or animal (111,152) sources have been published elsewhere and are not described here. Instead, a short overview focusing on the functional diversity of naturally occurring FAS systems emphasizes some specific facets of type I FASs which are discussed in more detail later in this review.…”

Section: General Principles and Functional Diversity In Biological Famentioning

confidence: 99%

“…These enzymes are contrasted by the highly integrated type I FAS multienzymes, which contain the various catalytic activities of the reaction sequence as discrete functional domains, either on a single polypeptide chain or, in some cases, on two different multifunctional proteins of comparable size. Type I FAS multienzymes are characteristically found in the eucaryotic cytoplasm (82,111,135) and, as a remarkable procaryotic exception, also among the mycolic acid producing subgroup of the Actinomycetales (13,144). The type I systems may be further subdivided according to the domain organization of the multifunctional proteins and, concomitantly, according to their subunit stoichiometry.…”

Section: Introductionmentioning

confidence: 99%

Microbial Type I Fatty Acid Synthases (FAS): Major Players in a Network of Cellular FAS Systems

Schweizer

Hofmann

2004

Microbiol Mol Biol Rev

325

286

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The present review focuses on microbial type I fatty acid synthases (FASs), demonstrating their structural and functional diversity. Depending on their origin and biochemical function, multifunctional type I FAS proteins form dimers or hexamers with characteristic organization of their catalytic domains. A single polypeptide may contain one or more sets of the eight FAS component functions. Alternatively, these functions may split up into two different and mutually complementing subunits. Targeted inactivation of the individual yeast FAS acylation sites allowed us to define their roles during the overall catalytic process. In particular, their pronounced negative cooperativity is presumed to coordinate the FAS initiation and chain elongation reactions. Expression of the unlinked genes, FAS1 and FAS2, is in part constitutive and in part subject to repression by the phospholipid precursors inositol and choline. The interplay of the involved regulatory proteins, Rap1, Reb1, Abf1, Ino2/Ino4, Opi1, Sin3 and TFIIB, has been elucidated in considerable detail. Balanced levels of subunits α and β are ensured by an autoregulatory effect of FAS1 on FAS2 expression and by posttranslational degradation of excess FAS subunits. The functional specificity of type I FAS multienzymes usually requires the presence of multiple FAS systems within the same cell. De novo synthesis of long-chain fatty acids, mitochondrial fatty acid synthesis, acylation of certain secondary metabolites and coenzymes, fatty acid elongation, and the vast diversity of mycobacterial lipids each result from specific FAS activities. The microcompartmentalization of FAS activities in type I multienzymes may thus allow for both the controlled and concerted action of multiple FAS systems within the same cell

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On the Structure of Fatty Acid Synthetase of Yeast

Cited by 160 publications

References 45 publications

Structure and function of eukaryotic fatty acid synthases

Structure and function of eukaryotic fatty acid synthases

Arabidopsis β-Ketoacyl-[Acyl Carrier Protein] Synthase I Is Crucial for Fatty Acid Synthesis and Plays a Role in Chloroplast Division and Embryo Development

Microbial Type I Fatty Acid Synthases (FAS): Major Players in a Network of Cellular FAS Systems

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