scholarly journals Insights into triterpene synthesis and unsaturated fatty-acid accumulation provided by chromosomal-level genome analysis of Akebia trifoliata subsp. australis

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Hui Huang ◽  
Juan Liang ◽  
Qi Tan ◽  
Linfeng Ou ◽  
Xiaolin Li ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Developmental Stages ◽  
De Novo ◽  
Acyl Carrier Protein ◽  
Repetitive Sequences ◽  
Gene Families ◽  
Terpene Synthase ◽  
Comparative Genomic

AbstractAkebia trifoliata subsp. australis is a well-known medicinal and potential woody oil plant in China. The limited genetic information available for A. trifoliata subsp. australis has hindered its exploitation. Here, a high-quality chromosome-level genome sequence of A. trifoliata subsp. australis is reported. The de novo genome assembly of 682.14 Mb was generated with a scaffold N50 of 43.11 Mb. The genome includes 25,598 protein-coding genes, and 71.18% (485.55 Mb) of the assembled sequences were identified as repetitive sequences. An ongoing massive burst of long terminal repeat (LTR) insertions, which occurred ~1.0 million years ago, has contributed a large proportion of LTRs in the genome of A. trifoliata subsp. australis. Phylogenetic analysis shows that A. trifoliata subsp. australis is closely related to Aquilegia coerulea and forms a clade with Papaver somniferum and Nelumbo nucifera, which supports the well-established hypothesis of a close relationship between basal eudicot species. The expansion of UDP-glucoronosyl and UDP-glucosyl transferase gene families and β-amyrin synthase-like genes and the exclusive contraction of terpene synthase gene families may be responsible for the abundant oleanane-type triterpenoids in A. trifoliata subsp. australis. Furthermore, the acyl-ACP desaturase gene family, including 12 stearoyl-acyl-carrier protein desaturase (SAD) genes, has expanded exclusively. A combined transcriptome and fatty-acid analysis of seeds at five developmental stages revealed that homologs of SADs, acyl-lipid desaturase omega fatty acid desaturases (FADs), and oleosins were highly expressed, consistent with the rapid increase in the content of fatty acids, especially unsaturated fatty acids. The genomic sequences of A. trifoliata subsp. australis will be a valuable resource for comparative genomic analyses and molecular breeding.

EXTH-27. MOLECULAR CHARACTERIZATION AND PRECLINICAL DEVELOPMENT OF NOVEL SMALL MOLECULE INHIBITOR SPECIFIC FOR WILD-TYPE IDH1 FOR FERROPTOSIS INDUCTION IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi169-vi169
Author(s):  
Kevin Murnan ◽  
Serena Tommasini-Ghelfi ◽  
Lisa Hurley ◽  
Corey Dussold ◽  
Daniel Wahl ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Plasma Membrane ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Therapeutic Modality ◽  
Wild Type ◽  
Genetic Ablation

Abstract Increased de novo synthesis, mobilization and uptake of fatty acids are required to provide sufficient lipids for membrane biogenesis in support of rapid tumor cell division and growth. In addition to their structural roles as components of the plasma membrane, fatty acid-derived lipids regulate ferroptotic cell death, a type of programmed cell death, when oxidized by iron-dependent lipoxygenase enzymes. De novo lipogenesis and the defense against oxidative lipid damage require large amounts of cytosolic NADPH. Our group has recently found that HGG up-regulate wild-type Isocitrate dehydrogenase 1 (referred to hereafter as ‘wt-IDH1high HGG’) to generate large quantities of cytosolic NADPH. RNAi-mediated knockdown of wt-IDH1, alone and in combination with radiation therapy (RT), slows the growth of patient-derived HGG xenografts, while overexpression of wt-IDH1 promotes intracranial HGG growth. Isotope tracer and liquid chromatography-based lipidomic studies indicated that wt-IDH1 supports the de novo biosynthesis of mono-unsaturated fatty acids (MUFAs) and promotes the incorporation of monounsaturated phospholipids into the plasma membrane, while displacing polyunsaturated fatty acid (PUFA) phospholipids. In addition, enhanced NADPH production in wt-IDH1high HGG increases glutathione (GSH) level, reduces reactive oxygen species (ROS), activates the phospholipid peroxidase glutathione peroxidase 4 (GPX4)-driven lipid repair pathway, and dampens the accumulation of PUFA-containing lipid peroxides, known executioners of ferroptosis. To pharmacologically target wt-IDH1,we have used and characterized wt-IDH1i-13, a first-in-class competitive α,β-unsaturated enone (AbbVie). wt-IDH1i-13 potently inhibits wt-IDH1 enzymatic activity, by covalently binding to the NADP+ binding pocket. Our data indicate that wt-IDH1i-13 promotes ferroptosis, which can be rescued by pre-treatment of cells with the peroxyl scavenger and ferroptosis inhibitor ferrostatin. wt-IDH1i-13 is brain-penetrant, and similar to genetic ablation, reduces progression and extends the survival of wt-IDH1high HGG bearing mice, alone and in combination with RT. These studies credential to wt-IDH1i-13 as a novel therapeutic modality for the treatment of wt-IDH1 gliomas.

Regulation Of The Fatty Acid Composition Of Platelet Phospholipids

1981 ◽  
Author(s):  
M L McKean ◽  
J B Smith ◽  
M J Silver
Keyword(s):  
Fatty Acids ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Membrane Phospholipids ◽  
De Novo Biosynthesis ◽  
Coa Transferase

The fatty acid composition of cell membrane phospholipids does not remain constant after de novo biosynthesis, but undergoes continual remodelling. One of the major routes for remodelling probably includes the deacylation-reacylation steps of the Lands Pathway. This has been shown to be important for the incorporation of long chain, polyunsaturated fatty acids into phospholipids by liver and brain. An understanding of the mechanisms involved in these processes in platelets is especially important in light of the large stores of arachidonic acid (AA) in platelet phospholipids and the role of AA in hemostasis and thrombosis. Previous results from this laboratory have shown that the turnover of radioactive AA, 8,11,14-eicosatrienoic and 5,8,11,14,17-eicosapentaenoic acids in the phospholipids of resting platelets is more rapid than the turnover of radioactive C16 and C18 saturated and unsaturated fatty acids. However, little is known about how fatty acids, especially AA and its homologues, are incorporated into platelet phospholipids during de novo biosynthesis or how they are exchanged during remodelling.At least three enzymes are involved in the deacylation- reacylation of phospholipids: phospholipase A2; acyl CoA synthetase; and acyl CoA transferase. We have studied acyl CoA transferase and have found considerable activity in human platelet membranes. Experiments are in progress to determine the substrate specificity and other properties of this enzyme.

scholarly journals Differentiation of Symphytum Species Using RAPD and Seed Fatty Acid Patterns

2010 ◽  
Vol 5 (4) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Tamer Özcan
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Developmental Stages ◽  
Fatty Acid Profiles ◽  
Morphological Descriptors ◽  
Rapd Primer ◽  
Fatty Acid Patterns ◽  
Genotypic Characteristics ◽  
Selection Of

RAPD and fatty acid profiles, and α-tocoferol contents of the seeds of some Symphytum species were analyzed for their differentiation. Discriminative patterns were found in the examined species. Genotypic characteristics of three Symphytum species were experienced using 20 decamer RAPD primers. The majority of band positions varied between species. The total amplified products of 20 RAPD primers was 247 (average of 12.35 bands per primer), of which 189 bands were polymorphic, corresponding to nearly 76.1% genetic diversity. The number of bands for each RAPD primer varied from 8 (UBC320) to 18 (OPA7). The percent of polymorphic bands ranged from 45.4% (OPJ20) to 93.3% (OPA16). Major unsaturated fatty acids in the seeds were linoleic, γ-linolenic and oleic acids; α-linolenic and eicosenoic acids exhibited lower levels. Variations in quantities and total ratios of fatty acid groups, and α-tocopherol contents were also observed between the species, and the developmental stages of the seeds. Significant differences were found for the whole series of fatty acids between species, in addition to the calculated ratios ( p < 0.05). Differences were also significant for fatty acid traits between two developmental stages of the seeds of endemic S. pseudobulbosum ( p < 0.05). In some morphological descriptors of the seeds, difference was found at a significant level ( p < 0.05). Obtained data based on genetic and biochemical variations seem to be useful for molecular delimitation of Symphytum, in addition to selection of the genotypes expressing a high amount of GLA.

Synthesis of Unsaturated Fatty Acids in Chick Embryo Liver

1971 ◽  
Vol 49 (5) ◽  
pp. 563-567 ◽  
Author(s):  
W. E. Donaldson ◽  
Nancy S. Mueller
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Saturated Fatty Acids ◽  
Acid Synthesis ◽  
Chick Embryos ◽  
Embryo Liver ◽  
Liver Homogenates ◽  
Cyclopropene Fatty Acids

Oxidation, synthesis, and desaturation of fatty acids were assessed in chick embryos and embryonic liver. No differences in the oxidation of palmitate-1-14C and oleate-1-14C by intact embryos and embryo-liver homogenates were found. De novo fatty acid synthesis and microsomal elongation of fatty acids were detected in embryo-liver homogenates, but the activities were low as compared with chick liver. The specific activities of the mitochondrial system of fatty acid elongation were similar in embryo and chick liver. Stimulation of the desaturation of stearic acid was achieved by the substitution of glucose for fatty acids in the culture medium and abolished by the addition of cyclopropene fatty acids to the medium. The hypothesis is advanced that in chick embryos, the rate of desaturation of fatty acids synthesized de novo is less than that of postembryonic liver, and that as a consequence, the liver of embryos cannot maintain the proportion of unsaturated to saturated fatty acids found in yolk.

Fatty acid composition and primer specificity of de novo fatty acid synthetase in Bacillus globispores, Bacillus insolitus, and Bacillus psychrophilus

1983 ◽  
Vol 29 (12) ◽  
pp. 1634-1641 ◽  
Author(s):  
Toshi Kaneda ◽  
Eleanor J. Smith ◽  
Devarray N. Naik
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Fatty Acid Synthetase ◽  
Gas Liquid Chromatography ◽  
Straight Chain ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Chain Fatty Acids

The fatty acid compositions of three psychrophilic species of Bacillus were determined by gas–liquid chromatography. The proportions of straight-chain fatty acids, branched-chain fatty acids, and unsaturated fatty acids were found to be 13.3, 86.7, and 26.1 % of the total cellular fatty acids for Bacillus globispores, 36.6, 63.4, and 25.1 % for Bacillus insolitus, and 6.9, 93.1, and 18.4% for Bacillus psychrophilus, respectively. In all three organisms the de novo fatty acid synthetase specificity towards acyl-CoA primers was butyryl-CoA > propionyl-CoA [Formula: see text] acetyl-CoA. This shows that B. insolitus, which has an unusually large proportion of straight-chain fatty acids for Bacillus, does not possess a different de novo fatty acid synthetase than the other two organisms. Therefore, the greater proportion of straight-chain fatty acids in B. insolitus may be explained by a large supply of straight-chain primer.

scholarly journals Targeted mutagenesis of ∆5 and ∆6 fatty acyl desaturases induce dysregulation of lipid metabolism in Atlantic salmon (Salmo salar)

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Jin ◽  
Alex K. Datsomor ◽  
Rolf E. Olsen ◽  
Jon Olav Vik ◽  
Jacob S. Torgersen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Target Genes ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Fatty Acyl ◽  
Targeted Mutagenesis ◽  
Plant Oil ◽  
Farmed Salmon

Abstract Background With declining wild fish populations, farmed salmon has gained popularity as a source for healthy long-chain highly unsaturated fatty acids (LC-HUFA). However, the introduction of plant oil in farmed salmon feeds has reduced the content of these beneficial LC-HUFA. The synthetic capability for LC-HUFAs depends upon the dietary precursor fatty acids and the genetic potential, thus there is a need for in-depth understanding of LC-HUFA synthetic genes and their interactions with other genes involved in lipid metabolism. Several key genes of LC-HUFA synthesis in salmon belong to the fatty acid desaturases 2 (fads2) family. The present study applied whole transcriptome analysis on two CRISPR-mutated salmon strains (crispants), 1) Δ6abc/5Mt with mutations in Δ5fads2, Δ6fads2-a, Δ6fads2-b and Δ6fads2-c genes, and 2) Δ6bcMt with mutations in Δ6fads2-b and Δ6fads2-c genes. Our purpose is to evaluate the genetic effect fads2 mutations have on other lipid metabolism pathways in fish, as well as to investigate mosaicism in a commercial species with a very long embryonal period. Results Both Δ6abc/5Mt and Δ6bcMt crispants demonstrated high percentage of indels within all intended target genes, though different indel types and percentage were observed between individuals. The Δ6abc/5Mt fish displayed several disruptive indels which resulted in over 100 differentially expressed genes (DEGs) enriched in lipid metabolism pathways in liver. This includes up-regulation of srebp1 genes which are known key transcription regulators of lipid metabolism as well as a number of down-stream genes involved in fatty acid de-novo synthesis, fatty acid β-oxidation and lipogenesis. Both elovl5 and elovl2 genes were not changed, suggesting that the genes were not targeted by Srebp1. The mutation of Δ6bcMt surprisingly resulted in over 3000 DEGs which were enriched in factors encoding genes involved in mRNA regulation and stability. Conclusions CRISPR-Cas9 can efficiently mutate multiple fads2 genes simultaneously in salmon. The results of the present study have provided new information on the transcriptional regulations of lipid metabolism genes after reduction of LC-HUFA synthesis pathways in salmon.

The influence of changes in dietary oil content on the fatty acid profile of backfat in pigs

1992 ◽  
Vol 1992 ◽  
pp. 185-185
Author(s):  
J. Wiseman ◽  
J.A. Agunbiade ◽  
D.J.A. Cole
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Profile ◽  
Dietary Fat ◽  
Unsaturated Fatty Acids ◽  
De Novo ◽  
Rate Of Change ◽  
Finishing Pigs ◽  
Relative Contribution ◽  
Dietary Oil

The fatty add profile of pig fat has profound effects upon both the eating and keeping quality of pig meat. Fatty adds within carcass fat may arise from two discrete sources, being de novo synthesis and direct deposition from fatty acids present In the diet. The relative contribution of these two routes, together with the fatty acid profile of dietary fat, will Influence the chemical composition of carcass fat. It is well established that diets containing high levels of unsaturated fatty acids will result in softer and oilier carcass fat and It Is often considered inappropriate to feed such diets during the finishing phase of pig growth. However the speed with which carcass fat reflects a change in dietary fat has not been quantified. The objective of the current trial was to measure the rate of change in fatty acid profile of carcass fat of finishing pigs following major changes in dietary fat.

scholarly journals Engineering of Fatty Acid Synthases (FASs) to Boost the Production of Medium-Chain Fatty Acids (MCFAs) in Mucor circinelloides

2019 ◽  
Vol 20 (3) ◽  
pp. 786 ◽  
Author(s):  
Syed Hussain ◽  
Ahsan Hameed ◽  
Md. Khan ◽  
Yao Zhang ◽  
Huaiyuan Zhang ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Acyl Carrier Protein ◽  
Fold Increase ◽  
Mucor Circinelloides ◽  
Palm Tree ◽  
Medium Chain ◽  
Health Related ◽  
Fatty Acid Synthases

Increasing energy demands and health-related concerns worldwide have motivated researchers to adopt diverse strategies to improve medium-chain fatty acid (MCFA) biosynthesis for use in the functional food and aviation industries. The abundance of naturally produced MCFAs from botanical sources (i.e., coconut fruit/seeds and palm tree) has been observed to be insufficient compared with the various microorganisms used to cope with industrial demands. Mucor circinelloides is one of many promising microorganisms; it exhibits diverse biotechnological importance ranging from the production of functional lipids to applications in the manufacture of bio-fuel. Thus, research was conducted to acquire the desired elevated amounts of MCFAs (i.e., C8–C12) from metabolically engineered strains of M. circinelloides M65. To achieve this goal, four different acyl-acyl carrier protein (ACP) thioesterase (TE)-encoding genes exhibiting a substrate preference for medium-chain acyl-ACP molecules were expressed in M. circinelloides M65, resulting in the generation of C8–C12 fatty acids. Among all the engineered strains, M65-TE-03 and M65-TE-04 demonstrated the highest production of non-native C8–C10 and C12 fatty acids, respectively, in comparison to the control. These recombinant strains biosynthesized MCFAs de novo within the range from 28 to 46% (i.e., 1.14 to 2.77 g/L) of total cell lipids. Moreover, the reduction in chain length eventually resulted in a 1.5–1.75-fold increase in total lipid productivity in the engineered strains. The MCFAs were also found to be integrated into all lipid classes. This work illustrates how the integration of heterologous enzymes in M. circinelloides can offer a novel opportunity to edit the fatty acid synthases (FAS) complex, resulting in increased production of microbial MFCAs.

scholarly journals The fractionation of the fatty acid synthetase activities of avocado mesocarp plastids

1975 ◽  
Vol 146 (2) ◽  
pp. 439-445 ◽  
Author(s):  
P J Weaire ◽  
R G O Kekwick
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
De Novo ◽  
Acyl Carrier Protein ◽  
Fatty Acid Synthetase ◽  
Carrier Protein ◽  
Acetyl Coa ◽  
Principal Product ◽  
Absolute Requirement ◽  
Malonyl Coa

1. The range of fatty acids formed by preparations of ultrasonically ruptured avocado mesocarp plastids was dependent on the substrate. Whereas [1-14C]palmitate and [14C]oleate were the major products obtained from [-14C]acetate and [1-14C]acetyl-CoA, the principal product from [2-14C]malonyl-CoA was [14-C]stearate. 2. Ultracentrifugation of the ruptured plastids at 105000g gave a supernatant that formed mainly stearate from [2-14C]malonyl-CoA and to a lesser extent from [1-14C]acetate. The incorporation of [1-14C]acetate into stearate by this fraction was inhibited by avidin. 3. The 105000g precipitate of the disrupted plastids incorporated [1-14C]acetate into a mixture of fatty acids that contained largely [14C]plamitate and [14C]oleate. The formation of [14C]palmitate and [14C]oleate by disrupted plastids was unaffected by avidin. 4. The soluble fatty acid synthetase was precipitated from the 105000g supernatant in the 35-65%-saturated-(NH4)2SO4 fraction and showed an absolute requirement for acyl-carrier protein. 5. Both fractions synthesized fatty acids de novo.

Lipid level and total fatty acid composition for selected developmental stages of Entomophthora egressa

1981 ◽  
Vol 27 (7) ◽  
pp. 670-674 ◽  
Author(s):  
Gary B. Dunphy ◽  
K. M. W. Keough ◽  
Richard A. Nolan
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Total Fatty Acid ◽  
Unsaturated Fatty Acids ◽  
Developmental Stages ◽  
Lipid Level ◽  
Total Fatty Acid Composition ◽  
Fatty Acid Unsaturation ◽  
Initial Stage ◽  
Hyphal Body

The major fatty acids (> 10%) of Entomophthora egressa were C16:0 and C18:1. Minor fatty acids, which varied with the stage of fungal development, included C11:0, C12:0, C13:0, C14:0, C15:0, C16:1, C17:0, C18:0, C18:2, C18:3, C20:1, C20:2, C20:3, C20:4, C20:5, and two unidentified unsaturated fatty acids. Differences were observed between the total fatty acid levels of C12:0, C14:0, C17:0, C18:0, and C20:5 and the degree of unsaturation of the fatty acids of 37-h protoplasts grown in modified Grace's medium and a simplified growth medium (SGM). The levels of C12:0, C14:0, C18:1, C20:4, and C20:5 decreased and the levels of C18:0 and C20:2 increased with the formation of spherical hyphal body (shb) initials. With the production of mature shb increased levels of C12:0, C14:0, C15:0, C18:1, C20:4, and C20:5 were detected. During the germination of the shb the levels of C14:0, C16:1, C18:1, and C20:4 increased, whereas C15:0 and C20:5 levels declined. The fatty acid levels, except for Cl2:0, C13:0, and C20:2, remained constant during the mycelial stage. The degree of fatty acid unsaturation decreased during early stages of development (protoplasts through shb initials). In SGM the degree of fatty acid unsaturation was lowest during the shb initial stage and highest during the shb stage. The total lipid level increased during shb maturation and declined during shb germination.

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