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Squalene synthase

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28336949/induction-of-apoptosis-and-ganoderic-acid-biosynthesis-by-camp-signaling-in-ganoderma-lucidum
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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