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Squalene synthase

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https://www.readbyqxmd.com/read/28921701/an-exception-among-diatoms-unique-organization-of-genes-involved-in-isoprenoid-biosynthesis-in-rhizosolenia-setigera-ccmp-1694
#1
Victor Marco Emmanuel N Ferriols, Ryoko Yaginuma-Suzuki, Kazunari Fukunaga, Takashi Kadono, Masao Adachi, Shigeki Matsunaga, Shigeru Okada
The marine diatom Rhizosolenia setigera is unique among this group of microalgae given that it is one of only a handful of diatom species that can produce highly branched isoprenoid (HBI) hydrocarbons. In our efforts to determine distinguishing molecular characteristics in R. setigera CCMP 1694 that could help elucidate the underlying mechanisms for its ability to biosynthesize HBIs, we discovered the occurrence of independent genes encoding for two isopentenyl diphosphate isomerases (RsIDI1 and RsIDI2) and one squalene synthase (RsSQS), enzymes that catalyze non-consecutive steps in isoprenoid biosynthesis...
September 15, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28901277/repositioning-of-tak-475-in-mevalonate-kinase-disease-translating-theory-into-practice
#2
Annalisa Marcuzzi, Claudia Loganes, Claudio Celeghini, Giulio Kleiner
Mevalonate Kinase Deficiency (MKD, OMIM #610377) is a rare autosomal recessive metabolic and inflammatory disease. In MKD, defective function of the enzyme mevalonate kinase (MK), due to a mutation in the MVK gene, leads to the shortage of mevalonate-derived intermediates, which results in unbalanced prenylation of proteins and altered metabolism of sterols. These defects lead to a complex multisystem inflammatory and metabolic syndrome. Although biologic therapies aimed at blocking the inflammatory cytokine interleukin-1 (IL-1) can significantly reduce inflammation, they cannot completely control the clinical symptoms that affects the nervous system...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28888597/mechanisms-linking-metabolic-stress-with-innate-immunity-in-the-endometrium
#3
I Martin Sheldon, James G Cronin, Mateusz Pospiech, Matthew L Turner
Bacterial infections of the uterus after parturition are ubiquitous in dairy cattle and often cause uterine disease, such as metritis or endometritis. However, the metabolic stress associated with milk production increases the risk of developing disease. Resolution of bacterial infections requires rapid and robust innate immune responses, which depend on host cell receptors recognizing pathogen-associated molecular patterns, such as lipopolysaccharide (LPS) from gram-negative bacteria. Here, we argue that metabolic stress impairs the inflammatory response to pathogens...
September 6, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28881416/improved-fruit-%C3%AE-tocopherol-carotenoid-squalene-and-phytosterol-content-through-manipulation-of-brassica-juncea-3-hydroxy-3-methylglutaryl-coa-synthase1-in-transgenic-tomato
#4
Pan Liao, Xinjian Chen, Mingfu Wang, Thomas J Bach, Mee-Len Chye
3-Hydroxy-3-methylglutaryl-coenzyme A synthase (HMGS) in the mevalonate (MVA) pathway generates isoprenoids including phytosterols. Dietary phytosterols are important because they can lower blood cholesterol levels. Previously, the overexpression of Brassica juncea wild-type (wt) and mutant (S359A) BjHMGS1 in Arabidopsis up-regulated several genes in sterol biosynthesis and increased sterol content. Recombinant S359A had earlier displayed a 10-fold higher in vitro enzyme activity. Furthermore, tobacco HMGS-overexpressors (OEs) exhibited improved sterol content, plant growth and seed yield...
September 7, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28881085/analysis-of-the-catalytic-mechanism-of-bifunctional-triterpene-sesquarterpene-cyclase-tyr167-functions-to-terminate-cyclization-of-squalene-at-the-bicyclic-step
#5
Liudmila Tenkovskaia, Mizuki Murakami, Kotone Okuno, Daijiro Ueda, Tsutomu Sato
Onoceroids are a group of triterpenes biosynthesized from squalene or dioxidosqualene by cyclization from both termini. We previously identified a bifunctional triterpene/sesquarterpene cyclase (TC) that constructs a tetracyclic scaffold from tetraprenyl-β-curcumene (C35 ) but a bicyclic scaffold from squalene (C30 ) in the first reaction. TC also accepts the bicyclic intermediate as a substrate and generates tetracyclic and pentacyclic onoceroids in the second reaction. In this study, we analyzed the catalytic mechanism of an onoceroid synthase by using mutated enzymes...
September 7, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28822179/-research-of-genes-expression-related-to-ginsenosides-biosynthesis-by-methyl-jasmonic-acid-in-ginseng-hair-roots
#6
Kang-Yu Wang, Li-Li Yu, Mei-Ping Zhang, Rui Yin, Yan-Ping Lin, Ming-Zhu Zhao, Chun-Yu Sun, Yi Wang
In order to obtain the expression of ginsenoside biosynthetic pathway related enzyme gene in ginseng hairy root under the control of elicitors, methyl jasmonate (MeJA) was added exogenously as elicitors. Ginseng hairy root clones induced by 4-year-old ginseng root was used as material, total saponin content in ginseng hairy root before and after MeJA treatment was determined by vanillin-sulfuric acid colorimetry, Meanwhile, relative expression of squalene synthase genes, squalene epoxidase genes, oxidized squalene cyclase genes, dammarenediol synthase genes, β-amyrin synthase genes, cycloartenol synthase genes before and after MeJA treatment were determined by Real-time PCR...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28813599/tetraterpene-synthase-substrate-and-product-specificity-in-the-green-microalga-botryococcus-braunii-race-l
#7
Hem R Thapa, Su Tang, James C Sacchettini, Timothy P Devarenne
Recently, the biosynthetic pathway for lycopadiene, a C40 tetraterpenoid hydrocarbon, was deciphered from the L race of Botryococcus braunii, an alga that produces hydrocarbon oils capable of being converted into combustible fuels. The lycopadiene pathway is initiated by the squalene synthase (SS)-like enzyme lycopaoctaene synthase (LOS), which catalyzes the head-to-head condensation of two C20 geranylgeranyl diphosphate (GGPP) molecules to produce C40 lycopaoctaene. LOS shows unusual substrate promiscuity for SS or SS-like enzymes by utilizing C15 farnesyl diphosphate (FPP) and C20 phytyl diphosphate in addition to GGPP as substrates...
August 25, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28728107/developing-potential-agents-against-atherosclerosis-design-synthesis-and-pharmacological-evaluation-of-novel-dual-inhibitors-of-oxidative-stress-and-squalene-synthase-activity
#8
Maria G Katselou, Alexios N Matralis, Angeliki P Kourounakis
For the treatment of multifactorial and complex diseases, it has become increasingly apparent that compounds acting at multiple targets often deliver superior efficacy compared to compounds with high specificity for only a single target. Based on previous studies demonstrating the important antioxidant and anti-hyperlipidemic effect of morpholine and 1,4-benzo(x/thi)azine derivatives (A-E), we hereby present the design, synthesis and pharmacological evaluation of novel dual-acting molecules as a therapeutic approach for atherosclerosis...
June 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28714761/gamma-irradiation-of-medicinally-important-plants-and-the-enhancement-of-secondary-metabolite-production
#9
P Vivek Vardhan, Lata I Shukla
PURPOSE: The profitable production of some important plant-based secondary metabolites (ginsenosides, saponins, camptothecin, shikonins etc.) in vitro by gamma irradiation is a current area of interest. We reviewed different types of secondary metabolites, their mode of synthesis and effect of γ-radiation on their yield for different plants, organs and in vitro cultures (callus, suspension, hairy root). Special effort has been made to review the biochemical mechanisms underlying the increase in secondary metabolites...
July 17, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/28710558/pathway-engineering-for-the-production-of-%C3%AE-amyrin-and-cycloartenol-in-escherichia-coli-a-method-to-biosynthesize-plant-derived-triterpene-skeletons-in-e-coli
#10
Miho Takemura, Rie Tanaka, Norihiko Misawa
Cycloartenol is biosynthetically the first sterol skeleton, which is metabolized to phytosterols such as β-sitosterol and stigmasterol. β-Amyrin is the most commonly occurring aglycone skeleton for oleanane-type saponins such as glycyrrhizin and saikosaponins. It has been regarded that these cyclic triterpenes are unable to be produced in Escherichia coli, while no reports are available on their production with E. coli. Here, we describe a method to synthesize triterpene skeletons from higher plants, including cycloartenol and β-amyrin...
July 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28674547/integrated-transcriptomic-and-metabolomic-analysis-of-five-panax-ginseng-cultivars-reveals-the-dynamics-of-ginsenoside-biosynthesis
#11
Yun Sun Lee, Hyun-Seung Park, Dong-Kyu Lee, Murukarthick Jayakodi, Nam-Hoon Kim, Hyun Jo Koo, Sang-Choon Lee, Yeon Jeong Kim, Sung Won Kwon, Tae-Jin Yang
Panax ginseng C.A. Meyer is a traditional medicinal herb that produces bioactive compounds such as ginsenosides. Here, we investigated the diversity of ginsenosides and related genes among five genetically fixed inbred ginseng cultivars (Chunpoong [CP], Cheongsun [CS], Gopoong [GO], Sunhyang [SH], and Sunun [SU]). To focus on the genetic diversity related to ginsenoside biosynthesis, we utilized in vitro cultured adventitious roots from the five cultivars grown under controlled environmental conditions. PCA loading plots based on secondary metabolite composition classified the five cultivars into three groups...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28667762/enhanced-isoprenoid-production-from-xylose-by-engineered-saccharomyces-cerevisiae
#12
Suryang Kwak, Soo Rin Kim, Haiqing Xu, Guo-Chang Zhang, Stephan Lane, Heejin Kim, Yong-Su Jin
Saccharomyces cerevisiae has limited capabilities for producing fuels and chemicals derived from acetyl-CoA, such as isoprenoids, due to a rigid flux partition toward ethanol during glucose metabolism. Despite numerous efforts, xylose fermentation by engineered yeast harboring heterologous xylose metabolic pathways was not as efficient as glucose fermentation for producing ethanol. Therefore, we hypothesized that xylose metabolism by engineered yeast might be a better fit for producing non-ethanol metabolites...
July 1, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28649699/a-wrky-transcription-factor-from-withania-somnifera-regulates-triterpenoid-withanolide-accumulation-and-biotic-stress-tolerance-through-modulation-of-phytosterol-and-defense-pathways
#13
Anup Kumar Singh, Sarma Rajeev Kumar, Varun Dwivedi, Avanish Rai, Shaifali Pal, Ajit K Shasany, Dinesh A Nagegowda
Withania somnifera produces pharmacologically important triterpenoid withanolides that are derived via phytosterol pathway; however, their biosynthesis and regulation remain to be elucidated. A jasmonate- and salicin-inducible WRKY transcription factor from W. somnifera (WsWRKY1) exhibiting correlation with withaferin A accumulation was functionally characterized employing virus-induced gene silencing and overexpression studies combined with transcript and metabolite analyses, and chromatin immunoprecipitation assay...
June 26, 2017: New Phytologist
https://www.readbyqxmd.com/read/28530827/overexpression-of-the-squalene-epoxidase-gene-alone-and-in-combination-with-the-3-hydroxy-3-methylglutaryl-coenzyme-a-gene-increases-ganoderic-acid-production-in-ganoderma-lingzhi
#14
De-Huai Zhang, Lu-Xi Jiang, Na Li, Xuya Yu, Peng Zhao, Tao Li, Jun-Wei Xu
The squalene epoxidase (SE) gene from the biosynthetic pathway of ganoderic acid (GA) was cloned and overexpressed in Ganoderma lingzhi. The strain that overexpressed the SE produced approximately 2 times more GA molecules than the wild-type (WT) strain. Moreover, SE overexpression upregulated lanosterol synthase gene expression in the biosynthetic pathway. These results indicated that SE stimulates GA accumulation. Then, the SE and 3-hydroxy-3-methylglutaryl coenzyme A (HMGR) genes were simultaneously overexpressed in G...
June 14, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28484475/de-novo-sequencing-and-transcriptome-analysis-reveal-key-genes-regulating-steroid-metabolism-in-leaves-roots-adventitious-roots-and-calli-of-periploca-sepium-bunge
#15
Jian Zhang, Xinglin Li, Fuping Lu, Shanying Wang, Yunhe An, Xiaoxing Su, Xiankuan Li, Lin Ma, Guangjian Han
Periploca sepium Bunge is a traditional medicinal plant, whose root bark is important for Chinese herbal medicine. Its major bioactive compounds are C21 steroids and periplocin, a kind of cardiac glycoside, which are derived from the steroid synthesis pathway. However, research on P. sepium genome or transcriptomes and their related genes has been lacking for a long time. In this study we estimated this species nuclear genome size at 170 Mb (using flow cytometry). Then, RNA sequencing of four different tissue samples of P...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28476317/evolution-structure-and-membrane-association-of-ndufaf6-an-assembly-factor-for-nadh-ubiquinone-oxidoreductase-complex-i
#16
Bernard D Lemire
The NADH:ubiquinone oxidoreductase (complex I) is the largest member of the mitochondrial respiratory chain. Its FMN cofactor accepts two electrons from NADH and transfers them to ubiquinone via a chain of iron-sulphur centers. A central core of 14 highly conserved subunits can couple electron transfer to proton translocation. The mammalian enzyme has an additional ~30 accessory subunits. Complex I has important bioenergetic and metabolic functions and is a known source of reactive oxygen species; these functions link it to a number of hereditary and degenerative diseases...
July 2017: Mitochondrion
https://www.readbyqxmd.com/read/28365988/improvement-of-squalene-production-from-co2-in-synechococcus-elongatus-pcc-7942-by-metabolic-engineering-and-scalable-production-in-a-photobioreactor
#17
Sun Young Choi, Jin-Young Wang, Ho Seok Kwak, Sun-Mi Lee, Youngsoon Um, Yunje Kim, Sang Jun Sim, Jong-Il Choi, Han Min Woo
The push-and-pull strategy for metabolic engineering was successfully demonstrated in Synechococcus elongatus PCC 7942, a model photosynthetic bacterium, to produce squalene from CO2. Squalene synthase (SQS) was fused to either a key enzyme (farnesyl diphosphate synthase) of the methylerythritol phosphate pathway or the β-subunit of phycocyanin (CpcB1). Engineered cyanobacteria with expression of a fusion CpcB1-SQS protein showed a squalene production level (7.16 ± 0.05 mg/L/OD730) that was increased by 1...
April 4, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28360334/a-genomic-dna-reporter-screen-identifies-squalene-synthase-inhibitors-that-act-cooperatively-with-statins-to-upregulate-the-low-density-lipoprotein-receptor
#18
Alastair G Kerr, Lawrence C S Tam, Ashley B Hale, Milena Cioroch, Gillian Douglas, Sarina Agkatsev, Olivia Hibbitt, Joseph Mason, James Holt-Martyn, Carole J R Bataille, Graham M Wynne, Keith M Channon, Angela J Russell, Richard Wade-Martins
Hypercholesterolemia remains one of the leading risk factors for the development of cardiovascular disease. Many large double-blind studies have demonstrated that lowering low-density lipoprotein (LDL) cholesterol using a statin can reduce the risk of having a cardiovascular event by approximately 30%. However, despite the success of statins, some patient populations are unable to lower their LDL cholesterol to meet the targeted lipid levels, due to compliance or potency issues. This is especially true for patients with heterozygous familial hypercholesterolemia who may require additional upregulation of the low-density lipoprotein receptor (LDLR) to reduce LDL cholesterol levels below those achievable with maximal dosing of statins...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28353148/molecular-and-biochemical-characterization-of-squalene-synthase-from-siraitia-grosvenorii
#19
Heling Su, Yongming Liu, Yalun Xiao, Yanlian Tan, Yunyan Gu, Bin Liang, Hongli Huang, Yaosheng Wu
OBJECTIVES: To clone and characterize the squalene synthase from Siraitia grosvenorii (SgSQS). RESULTS: The gene encoding SgSQS was cloned. SgSQS has 417 amino acid residues with an pI of 7.3. There are 32 phosphorylation sites in its sequence: S(48) as well as S(196) play important roles in regulation of enzyme activity. The enzyme is a monomeric protein with a cave-like active center formed by α helixes and has two transmembrane domains at its C-terminus. SgSQS mRNA expression in stem and root were about twice as much as that in leaf and peel...
March 28, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28349256/virus-induced-gene-silencing-of-the-two-squalene-synthase-isoforms-of-apple-tree-malus%C3%A2-%C3%A3-%C3%A2-domestica-l-negatively-impacts-phytosterol-biosynthesis-plastid-pigmentation-and-leaf-growth
#20
Sandra M Navarro Gallón, Carolina Elejalde-Palmett, Dimitri Daudu, Franziska Liesecke, Frédéric Jullien, Nicolas Papon, Thomas Dugé de Bernonville, Vincent Courdavault, Arnaud Lanoue, Audrey Oudin, Gaëlle Glévarec, Olivier Pichon, Marc Clastre, Benoit St-Pierre, Lucia Atehortùa, Nobuyuki Yoshikawa, Nathalie Giglioli-Guivarc'h, Sébastien Besseau
The use of a VIGS approach to silence the newly characterized apple tree SQS isoforms points out the biological function of phytosterols in plastid pigmentation and leaf development. Triterpenoids are beneficial health compounds highly accumulated in apple; however, their metabolic regulation is poorly understood. Squalene synthase (SQS) is a key branch point enzyme involved in both phytosterol and triterpene biosynthesis. In this study, two SQS isoforms were identified in apple tree genome. Both isoforms are located at the endoplasmic reticulum surface and were demonstrated to be functional SQS enzymes using an in vitro activity assay...
July 2017: Planta
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