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Squalene synthase

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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
#1
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 3, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28360334/a-genomic-dna-reporter-screen-identifies-squalene-synthase-inhibitors-which-act-cooperatively-with-statins-to-upregulate-the-low-density-lipoprotein-receptor
#2
Alastair G Kerr, Lawrence C S Tam, Ashley B Hale, Milena Cioroch, Gillian Douglas, Sarina Agkatsev, Olivia Hibbit, Joseph Mason, James Holt-Martyn, Carole J R Bataille, Graham M Wynne, Keith M Channon, Angela J Russell, Richard Wade-Martins
Hypercholesterolaemia remains one of the leading risk factors for the development of cardiovascular disease. Many large double-blind studies have demonstrated that lowering LDL-cholesterol using a statin can reduce the risk of having a cardiovascular event by ~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 heterozygous familial hypercholesterolaemia (heFH) patients 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...
March 30, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28353148/molecular-and-biochemical-characterization-of-squalene-synthase-from-siraitia-grosvenorii
#3
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
#4
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...
March 27, 2017: Planta
https://www.readbyqxmd.com/read/28336949/induction-of-apoptosis-and-ganoderic-acid-biosynthesis-by-camp-signaling-in-ganoderma-lucidum
#5
Bang-Jau You, Ni Tien, Miin-Huey Lee, Bo-Ying Bao, Yih-Shyuan Wu, Tsung-Chi Hu, Hong-Zin Lee
Apoptosis is an essential physiological process that controls many important biological functions. However, apoptosis signaling in relation to secondary metabolite biosynthesis in plants and fungi remains a mystery. The fungus Ganoderma lucidum is a popular herbal medicine worldwide, but the biosynthetic regulation of its active ingredients (ganoderic acids, GAs) is poorly understood. We investigated the role of 3',5'-cyclic adenosine monophosphate (cAMP) signaling in fungal apoptosis and GA biosynthesis in G...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322148/effects-of-exogenous-salicylic-acid-on-ganoderic-acid-biosynthesis-and-the-expression-of-key-genes-in-the-ganoderic-acid-biosynthesis-pathway-in-the-lingzhi-or-reishi-medicinal-mushroom-ganoderma-lucidum-agaricomycetes
#6
Peng-Fei Cao, Chen-Gao Wu, Zhi-Hao Dang, Liang Shi, Ai-Liang Jiang, Ang Ren, Ming-Wen Zhao
We demonstrate herein that salicylic acid (SA) can enhance ganoderic acid (GA) accumulation in the lingzhi or reishi medicinal mushroom Ganoderma lucidum. Following treatment with different concentrations of SA, the GA content was increased 22.72% to 43.04% compared with the control group. When the fungi were treated with 200 μmol/L SA at different times, the GA content was improved 10.21% to 35.24% compared with the control group. By choosing the optimum point based on response surface methodology, the GA content could be increased up to 229...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/28303229/cloning-and-characterization-of-squalene-synthase-and-cycloartenol-synthase-from-siraitia-grosvenorii
#7
Huan Zhao, Qi Tang, Changming Mo, Longhua Bai, Dongping Tu, Xiaojun Ma
Mogrosides and steroid saponins are tetracyclic triterpenoids found in Siraitia grosvenorii. Squalene synthase (SQS) and cycloartenol synthase (CAS) are key enzymes in triterpenoid and steroid biosynthesis. In this study, full-length cDNAs of SgSQS and SgCAS were cloned by a rapid amplification of cDNA-ends with polymerase chain reaction (RACE-PCR) approach. The SgSQS cDNA has a 1254 bp open reading frame (ORF) encoding 417 amino acids, and the SgCAS cDNA contains a 2298 bp ORF encoding 765 amino acids. Bioinformatic analysis showed that the deduced SgSQS protein has two transmembrane regions in the C-terminal...
March 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28294269/%C3%AE-amyrin-biosynthesis-catalytic-mechanism-and-substrate-recognition
#8
REVIEW
Tsutomu Hoshino
The enzymatic polycyclization reactions catalyzed by oxidosqualene (OXSQ) cyclases (OSCs) proceed with complete regio- and stereospecificity, leading to the formation of new C-C bonds and chiral centers and to the generation of diverse polycyclic sterols and triterpenoids. The diverse structural array is remarkable, and approximately 150 different carbon frameworks have been found. Detailed investigations on squalene-hopene cyclase (SHC) and lanosterol synthase (LaS) have been reported, but progress in the study of β-amyrin synthase, which is ubiquitously found in plants, has lagged in comparison...
March 15, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28157221/microbial-modulation-of-bacoside-a-biosynthetic-pathway-and-systemic-defense-mechanism-in-bacopa-monnieri-under-meloidogyne-incognita-stress
#9
Rupali Gupta, Akanksha Singh, Madhumita Srivastava, Vivek Singh, M M Gupta, Rakesh Pandey
Plant-associated beneficial microbes have been explored to fulfill the imperative function for plant health. However, their impact on the host secondary metabolite production and nematode disease management remains elusive. Our present work has shown that chitinolytic microbes viz., Chitiniphilus sp. MTN22 and Streptomyces sp. MTN14 singly as well as in combination modulated the biosynthetic pathway of bacoside A and systemic defense mechanism against Meloidogyne incognita in Bacopa monnieri. Interestingly, expression of bacoside biosynthetic pathway genes (3-Hydroxy-3-methylglutaryl coenzyme A reductase, mevalonate diphosphate decarboxylase, and squalene synthase) were upregulated in plants treated with the microbial combination in the presence as well as in absence of M...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092952/total-synthesis-of-zaragozic-acid-c-implementation-of-photochemical-c-sp-3-h-acylation
#10
Takahiro Kawamata, Masanori Nagatomo, Masayuki Inoue
Zaragozic acid C (1) was isolated as a potent squalene synthase inhibitor. The 2,8-dioxabicyclo[3.2.1]octane core of 1 is decorated with the three hydroxycarbonyl (C3,4,5), two hydroxy (C4,7), one acyloxy (C6), and one alkyl (C1) groups. Installation of the contiguous C4- and C5-fully substituted carbons presents a formidable synthetic challenge. Our approach to address this problem used a two-step photochemical C(sp(3))-H acylation. Persilylated d-gluconolactone 4 was derivatized into 3 with the 1,2-diketone moiety at the C5-tetrasubstituted center...
January 25, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27939849/a-squalene-synthase-protein-degradation-method-for-improved-sesquiterpene-production-in-saccharomyces-cerevisiae
#11
Bingyin Peng, Manuel R Plan, Panagiotis Chrysanthopoulos, Mark P Hodson, Lars K Nielsen, Claudia E Vickers
Sesquiterpenes are C15 isoprenoids with utility as fragrances, flavours, pharmaceuticals, and potential biofuels. Microbial fermentation is being examined as a competitive approach for bulk production of these compounds. Competition for carbon allocation between synthesis of endogenous sterols and production of the introduced sesquiterpene limits yields. Achieving balance between endogenous sterols and heterologous sesquiterpenes is therefore required to achieve economical yields. In the current study, the yeast Saccharomyces cerevisiae was used to produce the acyclic sesquiterpene alcohol, trans-nerolidol...
January 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/27894599/overexpression-of-the-homologous-lanosterol-synthase-gene-in-ganoderic-acid-biosynthesis-in-ganoderma-lingzhi
#12
De-Huai Zhang, Na Li, Xuya Yu, Peng Zhao, Tao Li, Jun-Wei Xu
Ganoderic acids (GAs) in Ganoderma lingzhi exhibit anticancer and antimetastatic activities. GA yields can be potentially improved by manipulating G. lingzhi through genetic engineering. In this study, a putative lanosterol synthase (LS) gene was cloned and overexpressed in G. lingzhi. Results showed that its overexpression (OE) increased the ganoderic acid (GA) content and the accumulation of lanosterol and ergosterol in a submerged G. lingzhi culture. The maximum contents of GA-O, GA-Mk, GA-T, GA-S, GA-Mf, and GA-Me in transgenic strains were 46...
February 2017: Phytochemistry
https://www.readbyqxmd.com/read/27886451/activity-of-fluorine-containing-analogues-of-wc-9-and-structurally-related-analogues-against-two-intracellular-parasites-trypanosoma-cruzi-and-toxoplasma-gondii
#13
María N Chao, Catherine Li, Melissa Storey, Bruno N Falcone, Sergio H Szajnman, Sergio M Bonesi, Roberto Docampo, Silvia N J Moreno, Juan B Rodriguez
Two obligate intracellular parasites, Trypanosoma cruzi, the agent of Chagas disease, and Toxoplasma gondii, an agent of toxoplasmosis, upregulate the mevalonate pathway of their host cells upon infection, which suggests that this host pathway could be a potential drug target. In this work, a number of compounds structurally related to WC-9 (4-phenoxyphenoxyethyl thiocyanate), a known squalene synthase inhibitor, were designed, synthesized, and evaluated for their effect on T. cruzi and T. gondii growth in tissue culture cells...
December 16, 2016: ChemMedChem
https://www.readbyqxmd.com/read/27884675/molecular-cloning-and-functional-analysis-of-squalene-synthase-ss-in-panax-notoginseng
#14
Dan Jiang, Qixian Rong, Yijun Chen, Qingjun Yuan, Ye Shen, Juan Guo, Yirui Yang, Liangping Zha, Huixiao Wu, Luqi Huang, Chunsheng Liu
Panax notoginseng (Burk.) F. H. Chen, which is a used traditional Chinese medicine known as Sanqi or Tianqi in China, is widely studied for its ability to accumulate the triterpene saponins. Squalene synthase (SS: EC 2.5.1.21) catalyzes the first enzymatic step from the central isoprenoid pathway toward sterol and triterpenoid biosynthesis. In this study, SS from P. notoginseng was cloned and investigated followed by its recombinant expression and preliminary enzyme activity. The nucleotide sequence of the ORF contains 1 248 nucleotides and encodes 415 amino acid residues with molecular weight of 47...
February 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27833811/phytogeographic-and-genetic-variation-in-sorbus-a-traditional-antidiabetic-medicine-adaptation-in-action-in-both-a-plant-and-a-discipline
#15
Anna Bailie, Sebastien Renaut, Eliane Ubalijoro, José A Guerrero-Analco, Ammar Saleem, Pierre Haddad, John T Arnason, Timothy Johns, Alain Cuerrier
Mountain ash (Sorbus decora and S. americana) is used by the Cree Nation of the James Bay region of Quebec (Eeyou Istchee) as traditional medicine. Its potential as an antidiabetic medicine is thought to vary across its geographical range, yet little is known about the factors that affect its antioxidant capacity. Here, we examined metabolite gene expression in relation to antioxidant activity, linking phytochemistry and medicinal potential. Samples of leaf and bark from S. decora and S. americana were collected from 20 populations at four different latitudes...
2016: PeerJ
https://www.readbyqxmd.com/read/27821754/the-biosynthetic-pathway-of-the-nonsugar-high-intensity-sweetener-mogroside-v-from-siraitia-grosvenorii
#16
Maxim Itkin, Rachel Davidovich-Rikanati, Shahar Cohen, Vitaly Portnoy, Adi Doron-Faigenboim, Elad Oren, Shiri Freilich, Galil Tzuri, Nadine Baranes, Shmuel Shen, Marina Petreikov, Rotem Sertchook, Shifra Ben-Dor, Hugo Gottlieb, Alvaro Hernandez, David R Nelson, Harry S Paris, Yaakov Tadmor, Yosef Burger, Efraim Lewinsohn, Nurit Katzir, Arthur Schaffer
The consumption of sweeteners, natural as well as synthetic sugars, is implicated in an array of modern-day health problems. Therefore, natural nonsugar sweeteners are of increasing interest. We identify here the biosynthetic pathway of the sweet triterpenoid glycoside mogroside V, which has a sweetening strength of 250 times that of sucrose and is derived from mature fruit of luo-han-guo (Siraitia grosvenorii, monk fruit). A whole-genome sequencing of Siraitia, leading to a preliminary draft of the genome, was combined with an extensive transcriptomic analysis of developing fruit...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27811076/pglox6-encoding-a-lipoxygenase-contributes-to-jasmonic-acid-biosynthesis-and-ginsenoside-production-in-panax-ginseng
#17
Shadi Rahimi, Yu-Jin Kim, Johan Sukweenadhi, Dabing Zhang, Deok-Chun Yang
Ginsenosides, the valuable pharmaceutical compounds in Panax ginseng, are triterpene saponins that occur mainly in ginseng plants. It was shown that in vitro treatment with the phytohormone jasmonic acid (JA) is able to increase ginsenoside production in ginseng plants. To understand the molecular link between JA biosynthesis and ginsenoside biosynthesis, we identified a JA biosynthetic 13-lipoxygenase gene (PgLOX6) in P. ginseng that promotes ginsenoside production. The expression of PgLOX6 was high in vascular bundles, which corresponds with expression of ginsenoside biosynthetic genes...
November 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/27771819/ethylene-promotes-mycelial-growth-and-ganoderic-acid-biosynthesis-in-ganoderma-lucidum
#18
Guang Zhang, Ang Ren, Fengli Wu, Hanshou Yu, Liang Shi, Mingwen Zhao
OBJECTIVE: To investigate the effects of ethylene, in the form of ethephon (2-chloroethylphosphonic acid), on mycelial growth and ganoderic acid (GA) accumulation in the higher basidiomycete Ganoderma lucidum. RESULTS: Treatment with both 10 and 15 mM ethephon enhanced the growth of G. lucidum on solid CYM plates and in CYM liquid medium. After optimization using response surface methodology, GA reached 33 mg/g dry cell weight (DW), an increase of 90 %, compared with the control...
February 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/27746309/fungal-elicitors-enhance-ginsenosides-biosynthesis-expression-of-functional-genes-as-well-as-signal-molecules-accumulation-in-adventitious-roots-of-panax-ginseng-c-a-mey
#19
Jinxin Li, Shujie Liu, Juan Wang, Jing Li, Dahui Liu, Jianli Li, Wenyuan Gao
In this work, we selected three fungi strains (Aspergillus niger, Aspergillus flavus and Aspergillus oryzae) as elicitors prepared from mycelium or fermentation broth to improve ginsenosides production in adventitious roots culture. The results showed that ginsenosides production (29.90±4.67mgg(-1)) was significantly enhanced upon elicitation with 200mgL(-1)A. niger elicitor prepared from mycelium, which was 3.52-fold of untreated group. HPLC-ESI-MS(n) analysis was performed, showing that ginsenoside Rb3 was present after treatment with the A...
December 10, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27725246/cdna-isolation-and-functional-characterization-of-squalene-synthase-gene-from-ornithogalum-caudatum
#20
Ming Liu, Li-Na Li, Yi-Ting Pan, Jian-Qiang Kong
As the first step of ongoing efforts to investigate the genes responsible for the biosynthesis of steroidal saponins in the medicinal plant Ornithogalum caudatum, this investigation reported the cDNA isolation, prokaryotic expression and functional characterization of squalene synthase (SQS) gene from O. caudatum for the first time. Specifically, two unigenes showing high sequence identity to SQS were retrieved from RNA-Taq data, and then a full-length OcSQS1 corresponding to the two unigenes was isolated from O...
October 7, 2016: Protein Expression and Purification
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