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Fatty Acid Biosynthesis (fatty + acid_biosynthesis)

Distribution by Scientific Domains

Life Sciences	52%
Chemistry	35%
Medical Sciences	11%

Selected Abstracts

PLASTID FATTY ACID BIOSYNTHESIS IN THE DIATOMS NITZSCHIA ALBA AND NITZSCHIA LAEVIS

JOURNAL OF PHYCOLOGY, Issue 2000
K.M. McGinnis
The role of the plastid in fatty acid biosynthesis in the non-photosynthetic diatom Nitzschia alba was studied and compared to that in the photosynthetic, closely related Nitzschia laevis. Transmission electron microscopy was used to analyze structural features of the plastid that may be relevant to biochemical function. Typical of a photosynthetic diatom, N. laevis had a chloroplast envelope composed of four membranes, and had abundant chloroplast ribosomes. The leucoplast of N. alba also had a multi-membrane envelope, chloroplast ribosomes, and a genome that encodes plastid specific proteins. This suggested that the plastid of N. alba may still possess the biochemical functions of the chloroplast, aside from photosynthesis. To determine whether plastidial fatty acid biosynthesis occurred in N. alba, the response of the two diatoms to the compound thiolactomycin was compared. Thiolactomycin has been shown to effect keto-acyl-ACP-synthases, and specifically inhibits the plastidial fatty acid biosynthetic pathway. While growth of N. alba was not impacted by thiolactomycin as in N. laevis, neutral lipid accumulation and fatty acid composition was impacted by thiolactomycin in both organisms. These findings suggest that the plastidial fatty acid biosynthetic pathway does exist in the leucoplast of N. alba, although it lacks photosynthetic capacity. [source]

Graminicide resistance in a blackgrass (Alopecurus myosuroides) population correlates with insensitivity of acetyl-CoA carboxylase

PLANT CELL & ENVIRONMENT, Issue 1 2004
L. J. PRICE
ABSTRACT The appearance of biotypes of the annual grass weed black-grass (Alopecurus myosuroides L. Huds), which are resistant to certain graminicides, is the most significant example of acquired resistance to herbicides seen so far in European agriculture. An investigation was perfomed into the basis of the specific cross-resistance to cyclohexanedione (CHD) and aryloxyphenoxypropionoic acid (AOPP) herbicides in the ,Notts A1' population of A. myosuroides, which survived treatment of fields with recommended rates of AOPP herbicides. In comparison with the wild-type ,Rothamsted' population, the resistant biotype showed over 100-fold resistance to these herbicides in a hydroponic growth system. Biosynthesis of fatty acids and activity of crude extracts of acetyl-CoA carboxylase (ACCase) were commensurately less sensitive to these herbicides in Notts A1 compared with the Rothamsted biotype. These data are consistent with the hypothesis that the highly resistant population has arisen through selection of a mutant ACCase which is much less sensitive to the AOPP and CHD graminicides. Rapidly growing cell suspension cultures established from the Notts A1 population also showed high resistance indices for CHD or AOPP herbicides compared with cultures from the Rothamsted biotype. Fatty acid biosynthesis and ACCase activity in the cell suspensions were similarly sensitive towards the graminicides to those in the foliar tissue counterparts of the resistant and sensitive populations. Moreover, purification of the main (chloroplast) isoform of acetyl-CoA carboxylase showed that this enzyme from the Notts A1 population was over 200-fold less sensitive towards the AOPP herbicide, quizalofop, than the equivalent isoform from the Rothamsted population. These data again fully supported the proposal that resistance in the Notts biotype is due to an insensitive acetyl-CoA carboxylase isoform. Overall, cell suspensions were also demonstrated to be excellent tools for further investigation of the molecular basis of the high level herbicide resistance which is prone to occur in A. myosuroides. [source]

Molecular responses of Campylobacter jejuni to cadmium stress

FEBS JOURNAL, Issue 20 2008
Nadeem O. Kaakoush
Cadmium ions are a potent carcinogen in animals, and cadmium is a toxic metal of significant environmental importance for humans. Response curves were used to investigate the effects of cadmium chloride on the growth of Camplyobacter jejuni. In vitro, the bacterium showed reduced growth in the presence of 0.1 mm cadmium chloride, and the metal ions were lethal at 1 mm concentration. Two-dimensional gel electrophoresis combined with tandem mass spectrometry analysis enabled identification of 67 proteins differentially expressed in cells grown without and with 0.1 mm cadmium chloride. Cellular processes and pathways regulated under cadmium stress included fatty acid biosynthesis, protein biosynthesis, chemotaxis and mobility, the tricarboxylic acid cycle, protein modification, redox processes and the heat-shock response. Disulfide reductases and their substrates play many roles in cellular processes, including protection against reactive oxygen species and detoxification of xenobiotics, such as cadmium. The effects of cadmium on thioredoxin reductase and disulfide reductases using glutathione as a substrate were studied in bacterial lysates by spectrophotometry and nuclear magnetic resonance spectroscopy, respectively. The presence of 0.1 mm cadmium ions modulated the activities of both enzymes. The interactions of cadmium ions with oxidized glutathione and reduced glutathione were investigated using nuclear magnetic resonance spectroscopy. The data suggested that, unlike other organisms, C. jejuni downregulates thioredoxin reductase and upregulates other disulfide reductases involved in metal detoxification in the presence of cadmium. [source]

A combined stress response analysis of Spirulina platensis in terms of global differentially expressed proteins, and mRNA levels and stability of fatty acid biosynthesis genes

FEMS MICROBIOLOGY LETTERS, Issue 2 2008
Wattana Jeamton
Abstract Changes in gene expression play a critical role in enhancing the ability of cyanobacteria to survive under cold conditions. In the present study, Spirulina platensis cultures were grown at the optimal growth temperature, in the light, before being transferred to dark conditions at 22 °C. Two dimensional-differential gel electrophoresis was then performed to separate differentially expressed proteins that were subsequently identified by MS. Among all differentiated proteins identified, a protein involved in fatty acid biosynthesis, (3R)-hydroxymyristoyl-[acyl-carrier-protein]-dehydratase encoded by fabZ, was the most up-regulated protein. However, the fatty-acid desaturation proteins were not significantly differentiated. This raised the question of how the unsaturated fatty acid, especially ,-linolenic acid, content in the cells in the cold,dark shift remained stable compared with that of the cold shift. Thus, a study at the transcriptional level of these desaturase genes, desC, desA and desD, and also of the fabZ gene was conducted. The results indicated that in the dark, where energy is limited, mRNA stability was enhanced by exposure to low temperatures. The data demonstrate that when the cells encounter cold stress with energy limitation, they can maintain their homeoviscous adaptation ability via mRNA stability. [source]

The fatty acid compositions of predator Piocoris luridus (Heteroptera: Lygaeidae) and its host Monosteria unicostata (Heteroptera: Tingidae) reared on almond

INSECT SCIENCE, Issue 6 2007
OZLEM CAKMAK
Abstract The changes in fatty acid compositions during nutritional interaction among almond Amygdalus communis Linnaeus (Rosales: Rosaceae) (host plant), lacebug Monosteria unicostata (Mulsant and Rey) (Heteroptera: Tingidae) and its predator Piocoris luridus Fieber (Heteroptera: Lygaeidae) were determined by gas chromatography and gas chromatography-mass spectrometry analyses. The fatty acid profiles of phospholipids and triacylglycerols were substantially different. Unlike the general observations for virtually most terrestrial insects, arachidonic and eicosapentaenoic acids were detected in high proportions of phospholipid fractions in both insects, especially in P. luridus. Also the almond tissues provide very little oleic acid to the herbivore diet, yet both insect species developed high proportions of this component. Our data reveals instances of specific accumulation of fatty acid biosynthesis, elongation/desaturation, and not incorporating selected fatty acids into cellular lipids. [source]

PLASTID FATTY ACID BIOSYNTHESIS IN THE DIATOMS NITZSCHIA ALBA AND NITZSCHIA LAEVIS

Legionella pneumophila couples fatty acid flux to microbial differentiation and virulence

MOLECULAR MICROBIOLOGY, Issue 5 2009
Rachel L. Edwards
Summary During its life cycle, Legionella pneumophila alternates between at least two phenotypes: a resilient, infectious form equipped for transmission and a replicative cell type that grows in amoebae and macrophages. Considering its versatility, we postulated that multiple cues regulate L. pneumophila differentiation. Beginning with a Biolog Phenotype MicroArray screen, we demonstrate that excess short-chain fatty acids (SCFAs) trigger replicative cells to cease growth and activate their panel of transmissive traits. To co-ordinate their response to SCFAs, L. pneumophila utilizes the LetA/LetS two-component system, but not phosphotransacetylase or acetyl kinase, two enzymes that generate high-energy phosphate intermediates. Instead, the stringent response enzyme SpoT appears to monitor fatty acid biosynthesis to govern transmission trait expression, as an altered distribution of acylated acyl carrier proteins correlated with the SpoT-dependent differentiation of cells treated with either excess SCFAs or the fatty acid biosynthesis inhibitors cerulenin and 5-(tetradecyloxy)-2-furoic acid. We postulate that, by exploiting the stringent response pathway to couple cellular differentiation to its metabolic state, L. pneumophila swiftly acclimates to stresses encountered in its host or the environment, thereby enhancing its overall fitness. [source]

Identification of protein differences between two clinical isolates of Streptococcus mutans by proteomic analysis

MOLECULAR ORAL MICROBIOLOGY, Issue 2 2008
L. H. Guo
Introduction:,Streptococcus mutans is generally considered to be the principal etiological agent for dental caries. Different strains of S. mutans may display different virulence mechanisms, so the isolation of the differential proteins is illuminating. Methods:,S. mutans strains 9-1 and 9-2, which both colonized the same oral cavity, were selected after screening for the possession of suspected virulence traits. The soluble cellular proteins were extracted from steady-state planktonic cells of strains 9-1 and 9-2 and were analyzed using high-resolution two-dimensional gel electrophoresis. Then, replicate maps of proteins from the two strains were generated. Proteins expressed only in strain 9-1 or 9-2 were excised and digested with trypsin by using an in-gel protocol. Tryptic digests were analyzed using matrix-assisted laser desorption/ionization time of flight mass spectrometry, by which peptide mass fingerprints were generated, and these were used to assign putative functions according to their homology with the translated sequences in the S. mutans genomic database. Results:, There were 12 proteins only expressed in strain 9-1 and three proteins only expressed in strain 9-2. They were involved in protein biosynthesis, protein folding, cell wall biosynthesis, fatty acid biosynthesis, nucleotide biosynthesis, repair of DNA damage, carbohydrate metabolism, signal transduction, and translation. Conclusion:, The identification of proteins differentially expressed between strains 9-1 and 9-2 provides new information concerning the mechanisms of cariogenesis. [source]

Evaluation of antiprotozoal and plasmodial enoyl-ACP reductase inhibition potential of turkish medicinal plants

PHYTOTHERAPY RESEARCH, Issue 2 2005
D. Tasdemir
Abstract A total of 58 extracts of different polarity were prepared from various organs of 16 species of Turkish plants and screened for their antitrypanosomal, antileishmanial and antiplasmodial activities. No significant activity was observed against Trypanosoma cruzi, whereas many extracts showed appreciable trypanocidal potential against T. brucei rhodesiense, with the CHCl3 -soluble portion of Phlomis kurdica being the most active (IC50 2.7 µg[sol ]mL). Almost all extracts, particularly the CHCl3 phases, exhibited growth inhibition activity against Leishmania donovani amastigotes. The CHCl3 -solubles of Putoria calabrica roots (IC50 1.9 µg[sol ]mL), Wendlandia ligustroides leaves (IC50 2.1 µg[sol ]mL) and Rhododendronluteum leaves (IC50 2.3 µg[sol ]mL) displayed the highest leishmanicidal potential. The majority of the extracts also possessed antiplasmodial activity against the multi-drug resistant K1 Plasmodium falciparum strain. The most potent antiplasmodial activity was observed with the CHCl3 extracts of Phlomis kurdica (IC50 1.5 µg[sol ]mL), P. leucophracta (IC50 1.6 µg[sol ]mL), Scrophularia cryptophila (IC50 1.8 µg[sol ]mL), Morina persica (IC50 1.9 µg[sol ]mL) and the aqueous root extract of Asperula nitida subsp. subcapitellata (IC50 1.6 µg[sol ]mL). Twenty-one extracts with significant antimalarial activity (IC50 < 5 µg[sol ]mL) were also tested for their ability to inhibit the purified enoyl-ACP reductase (FabI), a crucial enzyme in the fatty acid biosynthesis of P. falciparum. The CHCl3 extract of Rhododendronungernii leaves (IC50 10 µg[sol ]mL) and the H2O-soluble portion of Rhododendronsmirnovii leaves (IC50 0.4 µg[sol ]mL) strongly inhibited the FabI enzyme. The preliminary data indicate that some (poly)phenolic compounds are responsible for the FabI inhibition potential of these extracts. The presented work reports for the first time the antiprotozoal activity of nine different genera as well as a target specific antimalarial screening for the identification of P. falciparum FabI inhibitors from medicinal plant extracts. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Crystal structure of enoyl,acyl carrier protein reductase (FabK) from Streptococcus pneumoniae reveals the binding mode of an inhibitor

PROTEIN SCIENCE, Issue 4 2008
Jun Saito
Abstract Enoyl,acyl carrier protein (ACP) reductases are critical for bacterial type II fatty acid biosynthesis and thus are attractive targets for developing novel antibiotics. We determined the crystal structure of enoyl,ACP reductase (FabK) from Streptococcus pneumoniae at 1.7 Å resolution. There was one dimer per asymmetric unit. Each subunit formed a triose phosphate isomerase (TIM) barrel structure, and flavin mononucleotide (FMN) was bound as a cofactor in the active site. The overall structure was similar to the enoyl,ACP reductase (ER) of fungal fatty acid synthase and to 2-nitropropane dioxygenase (2-ND) from Pseudomonas aeruginosa, although there were some differences among these structures. We determined the crystal structure of FabK in complex with a phenylimidazole derivative inhibitor to envision the binding site interactions. The crystal structure reveals that the inhibitor binds to a hydrophobic pocket in the active site of FabK, and this is accompanied by induced-fit movements of two loop regions. The thiazole ring and part of the ureido moiety of the inhibitor are involved in a face-to-face ,,, stacking interaction with the isoalloxazine ring of FMN. The side-chain conformation of the proposed catalytic residue, His144, changes upon complex formation. Lineweaver,Burk plots indicate that the inhibitor binds competitively with respect to NADH, and uncompetitively with respect to crotonoyl coenzyme A. We propose that the primary basis of the inhibitory activity is competition with NADH for binding to FabK, which is the first step of the two-step ping-pong catalytic mechanism. [source]

Probing mechanisms of resistance to the tuberculosis drug isoniazid: Conformational changes caused by inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis

PROTEIN SCIENCE, Issue 8 2007
Nicole A. Kruh
Abstract The frontline tuberculosis drug isoniazid (INH) inhibits InhA, the NADH-dependent fatty acid biosynthesis (FAS-II) enoyl reductase from Mycobacterium tuberculosis (MTB), via formation of a covalent adduct with NAD+ (the INH-NAD adduct). Resistance to INH can be correlated with many mutations in MTB, some of which are localized in the InhA cofactor binding site. While the InhA mutations cause a substantial decrease in the affinity of InhA for NADH, surprisingly the same mutations result in only a small impact on binding of the INH-NAD adduct. Based on the knowledge that InhA interacts in vivo with other components of the FAS-II pathway, we have initiated experiments to determine whether enzyme inhibition results in structural changes that could affect protein,protein interactions involving InhA and how these ligand-induced conformational changes are modulated in the InhA mutants. Significantly, while NADH binding to wild-type InhA is hyperbolic, the InhA mutants bind the cofactor with positive cooperativity, suggesting that the mutations permit access to a second conformational state of the protein. While cross-linking studies indicate that enzyme inhibition causes dissociation of the InhA tetramer into dimers, analytical ultracentrifugation and size exclusion chromatography reveal that ligand binding causes a conformational change in the protein that prevents cross-linking across one of the dimer,dimer interfaces in the InhA tetramer. Interestingly, a similar ligand-induced conformational change is also observed for the InhA mutants, indicating that the mutations modulate communication between the subunits without affecting the two conformational states of the protein that are present. [source]

Both antisense and sense expression of biotin carboxyl carrier protein isoform 2 inactivates the plastid acetyl-coenzyme A carboxylase in Arabidopsis thaliana

THE PLANT JOURNAL, Issue 4 2002
Jay J. Thelen
Summary To further characterize the role of biotin carboxyl carrier protein isoform 2 (BCCP2) in acetyl-coenzyme A carboxylase (ACCase) function and fatty acid biosynthesis, plants with reduced or increased expression of this protein were characterized. Analysis of 38 independent Arabidopsis lines expressing antisense BCCP2 transcript behind a constitutive promoter showed no significant phenotype, though antisense transcript was highly expressed. In developing seed, BCCP2 protein was reduced by an average of 38% resulting in a 9% average decrease in fatty acid content in mature seed. Over-expression of BCCP2 behind a seed-specific napin promoter increased the amount of holo-BCCP2 in developing seed by an average of twofold, as determined with anti-biotin antibodies. Surprisingly, the average fatty acid content of T2 seed from over-expression lines was 23% lower than wild-type seed. These plants also exhibited reduced seed setting in 18 of 20 T1 lines which was coincident with increased individual seed mass. Quantification of total BCCP2 in developing siliques using anti-BCCP2 antibodies indicated that as much as 60% of total plastidial BCCP2 was in the non-biotinylated form (apo-BCCP2). Although apo-BCCP2 was highly over-expressed in developing seed, accumulation of other ACCase subunits was unaffected. The specific activity of ACCase was up to 65% lower in developing seed of over-expression lines versus wild type. This was attributed to the assembly of biologically inactive (non-biotinylated) ACCase complexes. Consistent with ACCase exerting control over de novo fatty acid synthesis, reduced activity in developing seed resulted in lower oil content, altered fatty acid composition and reduced seed setting. [source]

Imperfect pseudo-merohedral twinning in crystals of fungal fatty acid synthase

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2009
Simon Jenni
The recent high-resolution structures of fungal fatty acid synthase (FAS) have provided new insights into the principles of fatty acid biosynthesis by large multifunctional enzymes. The crystallographic phase problem for the 2.6,MDa fungal FAS was initially solved to 5,Å resolution using two crystal forms from Thermomyces lanuginosus. Monoclinic crystals in space group P21 were obtained from orthorhombic crystals in space group P212121 by dehydration. Here, it is shown how this space-group transition induced imperfect pseudo-merohedral twinning in the monoclinic crystal, giving rise to a Moiré pattern-like interference of the two twin-related reciprocal lattices. The strategy for processing the twinned diffraction images and obtaining a quantitative analysis is presented. The twinning is also related to the packing of the molecules in the two crystal forms, which was derived from self-rotation function analysis and molecular-replacement solutions using a low-resolution electron microscopy map as a search model. [source]

Discovery and Syntheses of "Superbug Challengers",Platensimycin and Platencin

CHEMISTRY - AN ASIAN JOURNAL, Issue 4 2010
Kalanidhi Palanichamy
Abstract Bacteria have developed resistance to almost all existing antibiotics known today and this has been a major issue over the last few decades. The search for a new class of antibiotics with a new mode of action to fight these multiply-drug-resistant strains, or "superbugs", allowed a team of scientists at Merck to discover two novel antibiotics, platensimycin and platencin using advanced screening strategies, as inhibitors of bacterial fatty acid biosynthesis, which is essential for the survival of bacteria. Though both these antibiotics are structurally related, they work by slightly different mechanisms and target different enzymes conserved in the bacterial fatty acid biosynthesis. This Focus Review summarizes the synthetic and biological aspects of these natural products and their analogues and congeners. [source]

Volatile Organic Compounds from Arctic Bacteria of the Cytophaga-Flavobacterium-Bacteroides Group: A Retrobiosynthetic Approach in Chemotaxonomic Investigations

CHEMISTRY & BIODIVERSITY, Issue 3 2005
Jeroen
Volatile organic compounds emitted by different marine arctic strains of the Cytophaga-Flavobacterium-Bacteroides group were investigated by using a modified closed-loop stripping apparatus (CLSA). Seven of nine strains emitted volatiles, dominated by methyl ketones, in specific patterns. The methyl ketones were aliphatic saturated, or unsaturated, and comprised 12 to 18 C-atoms, sometimes with terminal Me branches. They were identified by GC/MS, retention-index calculations, derivatization with dimethyl disulfide for CC bond location, and GC/FTIR to elucidate their uniform (Z)-configuration. The proposed structures of all methyl ketones were subsequently confirmed by synthesis, while the absolute configuration of chiral volatiles was elucidated by stereoselective synthesis. From retrobiosynthetic considerations, it was found that strain ARK10267 uses mainly valine, and strain ARK10063 mainly isoleucine for formation of starters for the ketone biosynthesis, which is correlated to fatty acid biosynthesis. Four strains (ARK10223, ARK10044, ARK10141, and ARK10146) use leucine. These separations are supported by phylogenetic affiliations based on 16S rRNA. Strain ARK10255b, in the course of this study found to be not a member of the Cytophaga-Flavobacterium-Bacteroides phylum, did not emit aliphatic ketones of medium chain length, but methionine-derived 4-(methylsulfanyl)butan-2-one and corresponding 4-(methylsulfanyl)butan-2-ol. Most of the compounds described have not been reported previously from nature. [source]

Genetic modification of the marine-derived yeast Yarrowia lipolytica with high-protein content using a GPI-anchor-fusion expression system

BIOTECHNOLOGY PROGRESS, Issue 5 2009
Fang Wang
Abstract Yarrowia lipolytica SWJ-1b isolated from the marine fish gut was found to contain 47.6 g of crude protein per 100 g of cell dry weight and had potential use as single cell protein. When the gene encoding enhanced green fluorescent protein (EGFP) was inserted into the surface display plasmid pINA1317-YlCWP110 and expressed in uracil mutant of Y. lipolytica SWJ-1b, the corresponding protein was successfully displayed on the cell surface, and 100% of the yeast cells exhibited the anchored target proteins. We found that yeast cells displaying EGFP were similar to those of Y. lipolytica SWJ-1b. Furthermore, C18:1 and C18:3 fatty acids biosynthesis in the marine yeast cells displaying the heterologous EGFP was weakly enhanced compared with that in its wild-type. The results suggest that the marine-derived Y. lipolytica SWJ-1b can be armed with the heterologous protein by the genetic modification and further used as single cell protein. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source]