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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA encoding beta-ketoacyl-ACP reductase (EC 1.1.1.100), an integral part of the fatty acid synthase type II, was cloned from Cuphea lanceolata. This cDNA of 1276 bp codes for a polypeptide of 320 amino acids with 63 N-terminal residues presumably representing a transit peptide and 257 residues corresponding to the mature protein of 27 kDa. The encoded protein shows strong homology with the amino-terminal sequence and two tryptic peptides from avocado mesocarp beta-ketoacyl-ACP reductase, and its total amino acid composition is highly similar to those of the beta-ketoacyl-ACP reductases of avocado and spinach. Amino acid sequence homologies to polyketide synthase, beta-ketoreductases and short-chain alcohol dehydrogenases are discussed. An engineered fusion protein lacking most of the transit peptide, which was produced in Escherichia coli, was isolated and proved to possess beta-ketoacyl-ACP reductase activity. Hybridization studies revealed that in C. lanceolata beta-ketoacyl-ACP reductase is encoded by a small family of at least two genes and that members of this family are expressed in roots, leaves, flowers and seeds.
Mol Gen Genet 1992 May
PMID:Isolation and characterization of a cDNA from Cuphea lanceolata encoding a beta-ketoacyl-ACP reductase. 137 2

A methodology was developed to construct any desired chromosomal mutation in the gene cluster that encodes the actinorhodin polyketide synthase (PKS) of Streptomyces coelicolor A3(2). A positive selection marker (resistance gene) is first introduced by double crossing-over into the chromosomal site of interest by use of an unstable delivery plasmid. This marker is subsequently replaced by the desired mutant allele via a second high-frequency double recombination event. The technology has been used to: (i) explore the significance of translational coupling between two adjacent PKS genes; (ii) prove that the acyl carrier protein (ACP) encoded by a gene in the cluster is necessary for the function of the actinorhodin PKS; (iii) provide genetic evidence supporting the hypothesis that serine 42 is the site of phosphopantetheinylation in the ACP of the actinorhodin PKS; and (iv) demonstrate that this ACP can be replaced by a Saccharopolyspora fatty acid synthase ACP to generate an active hybrid PKS.
Mol Microbiol 1992 Nov
PMID:Targeted gene replacements in a Streptomyces polyketide synthase gene cluster: role for the acyl carrier protein. 145 61

The onset of storage lipid biosynthesis during seed development in the oilseed crop Brassica napus (rape seed) coincides with a drastic qualitative and quantitative change in fatty acid composition. During this phase of storage lipid biosynthesis, the enzyme activities of the individual components of the fatty acid synthase system increase rapidly. We describe a rapid and simple purification procedure for the plastid-localized NADH-dependent enoyl-acyl carrier protein reductase from developing B. napus seed, based on its affinity towards the acyl carrier protein (ACP). The purified protein was N-terminally sequenced and used to raise a potent antibody preparation. Immuno-screening of a seed-specific lambda gt11 cDNA expression library resulted in the isolation of enoyl-ACP reductase cDNA clones. DNA sequence analysis of an apparently full-length cDNA clone revealed that the enoyl-ACP reductase mRNA is translated into a precursor protein with a putative 73 amino acid leader sequence which is removed during the translocation of the protein through the plastid membrane. Expression studies in Escherichia coli demonstrated that the full-length cDNA clone encodes the authentic B. napus NADH-dependent enoyl-ACP reductase. Characterization of the enoyl-ACP reductase genes by Southern blotting shows that the allo-tetraploid B. napus contains two pairs of related enoyl-ACP reductase genes derived from the two distinct genes found in both its ancestors, Brassica oleracea and B. campestris. Northern blot analysis of enoyl-ACP reductase mRNA steady-state levels during seed development suggests that the increase in enzyme activity during the phase of storage lipid accumulation is regulated at the level of gene expression.
Plant Mol Biol 1991 Oct
PMID:cDNA cloning and expression of Brassica napus enoyl-acyl carrier protein reductase in Escherichia coli. 191 3

The mRNAs for fatty acid synthase and malic enzyme were almost undetectable in total RNA extracted from the livers of 16-day old chick embryos. Both mRNAs increased in abundance between the 16th day of incubation and the day of hatching. In neonates, fatty acid synthase mRNA level was dependent on nutritional status, increasing slowly if the chicks were starved and rapidly if they were fed. The abundance of malic enzyme mRNA decreased in starved neonatal chicks and increased in fed ones. When neonates were first fed and then starved, starvation caused a large decrease in the abundance of both mRNAs. Conversely, feeding, after a period of starvation, resulted in a substantial increase in both mRNAs. The relative abundances of fatty acid synthase and malic enzyme mRNAs correlated positively with relative rates of enzyme synthesis. Thus, nutritional and hormonal regulation of the synthesis of these two 'lipogenic' enzymes is exerted primarily at a pre-translational level. The abundance of albumin mRNA decreased significantly between the 16th day of incubation and the day of hatching but did not change thereafter in fed or starved chicks. The relative stability of albumin mRNA levels after hatching attests to the selectivity of the nutritional regulation of fatty acid synthase and malic enzyme mRNAs. The decrease in albumin mRNA which occurred between 16 days of incubation and hatching contrasts with the increase in albumin mRNA sequences which occurred during late gestation in the fetal rat (20). High levels of albumin in the chick embryo may be related to the lack of an analogue of mammalian alpha-fetoprotein in birds.
Mol Cell Biochem 1984 Sep
PMID:Developmental and nutritional regulation of the messenger RNAs for fatty acid synthase, malic enzyme and albumin in the livers of embryonic and newly-hatched chicks. 620 76

Intravenous administration of a single dose (100 micrograms/kg bw) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats increased the rate of in vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to 14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue.
Mol Cell Biochem 1995 Feb 23
PMID:Metabolic effects of tumour necrosis factor-alpha on rat brown adipose tissue. 759 46

The effect of triiodothyronine (T3) on regulation of fatty acid synthase in chicken liver was investigated. In hypothyroid animals, enzyme activity was about one half of that in euthyroid animals. T3 treatment increased the enzyme activity in hypothyroid animals. There is little difference in both the mRNA concentration and the transcription rate between euthyroid and hypothyroid animals. T3 treatment markedly decreased both the mRNA concentration and the transcription rate in euthyroid and hypothyroid animals. These results suggested that T3 maintained the normal level of enzyme expression primarily by stimulating the post-transcriptional step, while the transcription of the gene was inhibited by hyperthyroidism.
Mol Cell Biochem 1995 Mar 23
PMID:Thyroid hormone inhibits fatty acid synthase gene transcription in chicken liver. 762 81

We have previously shown that triiodothyronine (T3) regulates rat fatty acid synthesis in a tissue specific manner. Here, we determined the effects of thyroid state on mRNAs encoding the lipogenic enzymes, acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS). S14 mRNA, a sequence tightly associated with lipogenesis, was also measured. Levels of the three mRNA were 9-13-fold higher in hyper- than hypothyroid liver. Limited expression in kidney and heart was also increased by thyroid hormone. In brown adipose tissue, highest levels were recorded in hypothyroid animals. Thyroid state did not affect expression in lung and brain. All these changes are consistent with those previously measured in fatty acid synthesis. In white adipose tissue, mRNA expression was increased by hyperthyroidism. This increase may not be reflected in fatty acid synthesis, since we recently showed lipogenesis to be reduced under these circumstances. All three mRNAs responded rapidly to T3 in liver, but more slowly in kidney and fat. Thus, T3 regulates lipogenesis by altering levels of ACC and FAS mRNAs. S14 mRNA changes in parallel.
Mol Cell Endocrinol 1995 Apr 28
PMID:Tissue-specific regulation of lipogenic mRNAs by thyroid hormone. 767 39

Thyroid hormones and insulin regulate numerous cell processes and potentially interact through the transcriptional regulation of key genes. For instance, thyroid hormones stimulate the transcription of the fatty acid synthase and malic enzyme genes in chick embryonic hepatocytes, while insulin amplifies these effects. It is possible that insulin augments these actions of thyroid hormone by stimulating production of the thyroid hormone nuclear receptor (TR). In these studies, we examined the regulation of TR production/gene expression by insulin in bovine aortic endothelial cells (BAEC). We demonstrate that insulin significantly stimulates the gene expression of the TR alpha receptor, from BAEC. Insulin causes a maximal threefold induction above control TR alpha steady state mRNA levels in time and dose-related fashion in these cells. The increased mRNA mainly resulted from a twofold increase in transcription, as determined by nuclear run on. Insulin also increases thyroid receptor number and thyroid hormone binding, determined by Scatchard analysis of competitive inhibition binding studies. An established observation is that insulin can synergistically augment thyroid hormone-induced transcriptional activation of several important genes. It has also been previously determined that thyroid hormone action correlates closely to TR nuclear receptor number. Therefore, our studies, which show that insulin stimulates TR alpha production, suggests a potential mechanism whereby insulin can augment thyroid hormone transcriptional action.
Mol Cell Endocrinol 1994 Jul
PMID:Insulin stimulates thyroid hormone receptor alpha gene expression in cultured bovine aortic endothelial cells. 795 99

Cerulenin, an antifungal antibiotic produced by Cephalosporium caerulens, is a potent inhibitor of fatty acid synthase in various organisms, including Saccharomyces cerevisiae. The antibiotic inhibits the enzyme by binding covalently to the active center cysteine of the condensing enzyme domain. We isolated 12 cerulenin-resistant mutants of S. cerevisiae following treatment with ethyl methanesulfonate. The mechanism of cerulenin resistance in one of the mutants, KNCR-1, was studied. Growth of the mutant was over 20 times more resistant to cerulenin than that of the wild-type strain. Tetrad analysis suggested that all mutants mapped at the same locus, FAS2, the gene encoding the alpha subunit of the fatty acid synthase. The isolated fatty acid synthase, purified from the mutant KNCR-1, was highly resistant to cerulenin. The cerulenin concentration causing 50% inhibition (IC50) of the enzyme activity was measured to be 400 microM, whereas the IC50 value was 15 microM for the enzyme isolated from the wild-type strain, indicating a 30-fold increase in resistance to cerulenin. The FAS2 gene was cloned from the mutant. Sequence replacement experiments suggested that an 0.8 kb EcoRV-HindIII fragment closely correlated with cerulenin resistance. Sequence analysis of this region revealed that the GGT codon encoding Gly-1257 of the FAS2 gene was altered to AGT in the mutant, resulting in the codon for Ser. Furthermore, a recombinant FAS2 gene, in which the 0.8 Kb EcoRV-HindIII fragment of the wild-type FAS2 gene was replaced with the same region from the mutant, when introduced into FAS2-defective S. cerevisiae complemented the FAS2 phenotype and showed cerulenin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Gen Genet 1994 Jul 08
PMID:Cerulenin-resistant mutants of Saccharomyces cerevisiae with an altered fatty acid synthase gene. 804 67

The malonyl coenzyme A-acyl carrier protein transacylase, a single polypeptide chain of 358 amino acid residues and a molecular mass of 32 kDa, is a key component of the fatty acid synthase multienzyme complex. The elucidation of its three-dimensional structure will help in the understanding of the molecular basis of the biosynthesis of fatty acids, as well as of polyketides and related biologically active molecules. Three X-ray-quality crystal forms of the Escherichia coli fabD gene product encoding for malonyl coenzyme A-acyl carrier protein transacylase have been obtained using the hanging-drop method and ammonium sulfate as precipitant. Two are tetragonal and each contains two molecules in the asymmetric unit (form I: space group P4(3(1))2(1)2 with a = b = 83.9 A, c = 166.5 A and form II: space group P4 with a = b = 132.64 A, c = 38.85 A), whereas the third form belongs to the hexagonal system and contains one molecule in the asymmetric unit (space group P6(1(5)) with a = b = 68.52 A, c = 117.71 A). In each case, the diffraction pattern extends to approximately 2.0 A resolution using CuK alpha radiation from a rotating anode source.
J Mol Biol 1994 Sep 09
PMID:Crystallization of the malonyl coenzyme A-acyl carrier protein transacylase from Escherichia coli. 807 74


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