Two genes of the putative mitochondrial fatty acid synthase in the genome of Saccharomyces cerevisiae

Schneider, Ralf; Brors, Benedikt; Bürger, Frank; Camrath, Stefan; Weiss, Hanns

doi:10.1007/s002940050292

Cited by 76 publications

(81 citation statements)

References 17 publications

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“…Dicots and most monocot plants contain a heteromeric ACC in their plastids consisting of four dissociable subunits with one of them being encoded by the plastid DNA (16,18). This structure of chloroplast ACC corresponding to the multisubunit composition of Escherichia coli ACC agrees with the putative procaryotic origin of the organelle and compares well with the dissociated structures of chloroplast and mitochondrial fatty-acid synthases (2)(3)(4)14). In contrast, the chloroplast ACC of Graminaceae exhibits the multifunctional characteristics of cytoplasmic ACC enzymes (18).…”

Section: Discussionmentioning

confidence: 56%

“…Cytoplasmic FAS is a multifunctional enzyme (type I-FAS) and synthesizes the bulk (Ͼ95%) of cellular fatty acids. In contrast, mitochondrial FAS is structurally similar to the non-aggregated FAS enzymes found in most bacteria where each component activity is represented by a distinct protein (type II-FAS) (2)(3)(4). Both FAS systems are encoded by nuclear genes.…”

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confidence: 99%

“…Both FAS systems are encoded by nuclear genes. Although mutational loss of cytoplasmic FAS gives rise to a fatty acid-requiring phenotype (5), mutants defective in one of the mitochondrial FAS-encoding genes are fatty acid-prototrophic but fail to grow on non-fermentative media (2)(3)(4). In accordance with these findings, Brody et al (2) and Wada et al (6) working with either yeast or plant systems suggest that a major function of mitochondrial FAS refers to lipoic acid synthesis by providing the octanoylacyl-carrier protein precursor of this cofactor.…”

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confidence: 99%

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HFA1 Encoding an Organelle-specific Acetyl-CoA Carboxylase Controls Mitochondrial Fatty Acid Synthesis in Saccharomyces cerevisiae

Hoja

Marthol

Hofmann

et al. 2004

Journal of Biological Chemistry

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The Saccharomyces cerevisiae gene, HFA1, encodes a >250-kDa protein, which is required for mitochondrial function. Hfa1p exhibits 72% overall sequence similarity (54% identity) to ACC1-encoded yeast cytoplasmic acetyl-CoA carboxylase. Nevertheless, HFA1 and ACC1 functions are not overlapping because mutants of the two genes have different phenotypes and do not complement each other. Whereas ACC1 is involved in cytoplasmic fatty acid synthesis, the phenotype of hfa1⌬ disruptants resembles that of mitochondrial fatty-acid synthase mutants. They fail to grow on lactate or glycerol, and the mitochondrial cofactor, lipoic acid, is reduced to <10% of its normal cellular concentration. Other than Acc1p, the N-terminal sequence of Hfa1p comprises a canonical mitochondrial targeting signal together with a matrix protease cleavage site. Accordingly, the HFA1-encoded protein was specifically assigned by Western blotting of appropriate cell fractions to the mitochondrial compartment. Removal of the mitochondrial targeting sequence abolished the competence of HFA1 DNA to complement hfal null mutants. Conversely and in contrast to the intact HFA1 sequence, the signal sequence-free HFA1 gene complemented the mutational loss of cytoplasmic acetyl-CoA carboxylase. Expression of HFA1 under the control of the ACC1 promoter restored cellular ACC activity in ACC1-defective yeast mutants to wild type levels. From this finding, it is concluded that HFA1 encodes a specific mitochondrial acetyl-CoA carboxylase providing malonyl-CoA for intraorganellar fatty acid and, in particular, lipoic acid synthesis.

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Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 99%

mentioning

confidence: 99%

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HFA1 Encoding an Organelle-specific Acetyl-CoA Carboxylase Controls Mitochondrial Fatty Acid Synthesis in Saccharomyces cerevisiae

Hoja

Marthol

Hofmann

et al. 2004

Journal of Biological Chemistry

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“…Plants synthesize fatty acids within the plastids, and use a discrete and highly conserved group of dissociated enzymes named fatty acid synthase system type 2 (FASII) [6]. This system, similarily to the eukaryotic mitochondrial FAS [7][8][9][10], differs from the mammalian cytosolic fatty acid synthase system type 1 (FASI) where all reactions are carried out by a single multifunctional polypeptide [11]. Fatty acids synthesized within plastid are exported to endoplasmic reticulum (ER) for elongation, resulting in the formation of VLCFAs that are essential cellular precursors of waxes, seed storage lipids and sphingolipids [5].…”

Section: Introductionmentioning

confidence: 99%

Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

et al. 2005

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Genes encoding enzymes involved in biosynthesis of very long chain fatty acids were significantly up-regulated during early cotton fiber development. Two cDNAs, GhKCR1 and GhKCR2 encoding putative cotton 3-ketoacyl-CoA reductases that catalyze the second step in fatty acid elongation, were isolated from developing cotton fibers. GhKCR1 and 2 contain open reading frames of 963 bp and 924 bp encoding proteins of 320 and 307 amino acid residues, respectively. Quantatitive RT-PCR analysis showed that both these genes were highly preferentially expressed during the cotton fiber elongation period with much lower levels recovered from roots, stems and leaves. GhKCR1 and 2 showed 30%-32% identity to Saccharomyces cerevisiae Ybr159p at the deduced amino acid level. These cotton cDNAs were cloned and expressed in yeast haploid ybr159w∆ mutant that was deficient in 3-ketoacyl-CoA reductase activity. Wild-type growth rate was restored in ybr159w∆ cells that expressed either GhKCR1 or 2. Further analysis showed that GhKCR1 and 2 were co-sedimented within the membranous pellet fraction after high-speed centrifugation, similar to the yeast endoplasmic reticulum marker ScKar2p. Both GhKCR(s) showed NADPH-dependent 3-ketoacyl-CoA reductase activity in an in vitro assay system using palmitoyl-CoA and malonyl-CoA as substrates. Our results suggest that GhKCR1 and 2 are functional orthologues of ScYbr159p.

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“…A potential role of mitochondrial ACP in fatty acid biosynthesis was suggested by incorporation of radioactivity from [2-14 C]malonate into acyl-ACPs in mitochondria isolated from Pisum sativum (17) and Neurospora crassa (18). The nuclear genes, ACP1 (15), CEM1 (19), MCT1 (20), OAR1 (20), and Ybr026p (21) of Saccharomyces cerevisiae, Etr1p (21) of Candida tropicalis, mtACP-1 of Arabidopsis thaliana (16), and HsNRBF-1p of Homo sapiens (22), have been implicated in mitochondrial fatty acid synthesis. Inactivation of these yeast genes resulted in a respiration-deficient phenotype (19 -21, 23).…”

mentioning

confidence: 99%

Identification and Molecular Characterization of the β-Ketoacyl-[Acyl Carrier Protein] Synthase Component of the Arabidopsis Mitochondrial Fatty Acid Synthase

Yasuno

Wettstein-Knowles

Wada

2004

Journal of Biological Chemistry

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Substrate specificity of condensing enzymes is a predominant factor determining the nature of fatty acyl chains synthesized by type II fatty acid synthase (FAS) enzyme complexes composed of discrete enzymes. The gene (mtKAS) encoding the condensing enzyme, ␤-ketoacyl-[acyl carrier protein] (ACP) synthase (KAS), constituent of the mitochondrial FAS was cloned from Arabidopsis thaliana, and its product was purified and characterized. The mtKAS cDNA complemented the KAS II defect in the E. coli CY244 strain mutated in both fabB and fabF encoding KAS I and KAS II, respectively, demonstrating its ability to catalyze the condensation reaction in fatty acid synthesis. In vitro assays using extracts of CY244 containing all E. coli FAS components, except that KAS I and II were replaced by mtKAS, gave C 4 -C 18 fatty acids exhibiting a bimodal distribution with peaks at C 8 and C 14 -C 16 . Previously observed bimodal distributions obtained using mitochondrial extracts appear attributable to the mtKAS enzyme in the extracts. Although the mtKAS sequence is most similar to that of bacterial KAS IIs, sensitivity of mtKAS to the antibiotic cerulenin resembles that of E. coli KAS I. In the first or priming condensation reaction of de novo fatty acid synthesis, purified His-tagged mtKAS efficiently utilized malonyl-ACP, but not acetyl-CoA as primer substrate. Intracellular targeting using green fluorescent protein, Western blot, and deletion analyses identified an N-terminal signal conveying mtKAS into mitochondria. Thus, mtKAS with its broad chain length specificity accomplishes all condensation steps in mitochondrial fatty acid synthesis, whereas in plastids three KAS enzymes are required.Fatty acids are synthesized by the enzymatic reactions of acetyl-CoA carboxylase (ACCase) 1 and fatty acid synthase (FAS). FAS enzyme complexes are classified into two groups based on their structural forms and organization. Complexes consisting of multifunctional polypeptides encoded by one or two genes (type I) are present in the cytoplasm of animals and fungi (1, 2), whereas those composed of monofunctional enzymes (type II) are present in most bacteria and plant plastids (3, 4) as well as in mitochondria, as will be detailed below. The incipient reaction of fatty acid synthesis is catalyzed by ACCase to form malonyl-CoA from acetyl-CoA, the initial carbon source. The first FAS activity, malonyl-CoA:ACP transacylase (MCAT), transfers the malonyl group from CoA to acyl carrier protein (ACP) to form the donor substrate malonyl-ACP that provides the C 2 -units for elongation. Repetitive elongation cycles accomplished by FAS start with condensation of the acyl primer substrate with the C 2 -unit to give a ␤-ketoacyl-ACP. The introduced ␤-keto group is then removed by three reactions, a ␤-keto reduction, a ␤-dehydration, and an enoyl reduction. The resulting saturated acyl-ACP serves as a substrate for the next extension. Most frequently seven or eight cycles yield palmitoyl (C 16 )-ACP and stearoyl (C 18 )-ACP, respectively. Additional FAS ac...

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Two genes of the putative mitochondrial fatty acid synthase in the genome of Saccharomyces cerevisiae

Cited by 76 publications

References 17 publications

HFA1 Encoding an Organelle-specific Acetyl-CoA Carboxylase Controls Mitochondrial Fatty Acid Synthesis in Saccharomyces cerevisiae

HFA1 Encoding an Organelle-specific Acetyl-CoA Carboxylase Controls Mitochondrial Fatty Acid Synthesis in Saccharomyces cerevisiae

Cloning and functional characterization of two cDNAs encoding NADPH-dependent 3-ketoacyl-CoA reductased from developing cotton fibers

Identification and Molecular Characterization of the β-Ketoacyl-[Acyl Carrier Protein] Synthase Component of the Arabidopsis Mitochondrial Fatty Acid Synthase

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