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Squalene synthase

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https://www.readbyqxmd.com/read/29775232/mannosylinositol-phosphorylceramides-and-ergosterol-coodinately-maintain-cell-wall-integrity-in-the-yeast-saccharomyces-cerevisiae
#1
Seiya Tanaka, Motohiro Tani
In the yeast Saccharomyces cerevisiae, complex sphingolipids have three types of polar head group, and breakdown of the normal composition causes several cellular dysfunctions. Previously we found that loss of biosynthesis of mannosylinositol phosphorylceramide (MIPC) causes a defect in cell wall integrity. In this study, we screened for multicopy suppressor genes that rescue the defect in cell wall integrity in cells lacking MIPC synthases (Sur1 and Csh1), and found that the defect is partly suppressed by upregulation of ergosterol biosynthesis...
May 18, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29732977/rational-discovery-of-novel-squalene-synthase-inhibitors-through-pharmacophore-modelling
#2
Avani B Chokshi, Mahesh T Chhabria, Pritesh R Desai
INTRODUCTION: In the present research work, a pharmacophore based virtual screening was performed using Discovery Studio 2.1 for the discovery of some novel molecules as inhibitors of Squalene Synthase Enzyme, a key enzyme in cholesterol biosynthetic pathway. Methos: A quantitative pharmacophore HypoGen was generated and the best HypoGen, had two ring aromatic and one hydrogen bond acceptor lipid features. The best HypoGen showed a very good correlation coefficient (r = 0.901) with satisfactory cost analysis...
May 7, 2018: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/29710800/discovery-of-potential-inhibitors-of-squalene-synthase-from-traditional-chinese-medicine-based-on-virtual-screening-and-in-vitro-evaluation-of-lipid-lowering-effect
#3
Yankun Chen, Xi Chen, Ganggang Luo, Xu Zhang, Fang Lu, Liansheng Qiao, Wenjing He, Gongyu Li, Yanling Zhang
Squalene synthase (SQS), a key downstream enzyme involved in the cholesterol biosynthetic pathway, plays an important role in treating hyperlipidemia. Compared to statins, SQS inhibitors have shown a very significant lipid-lowering effect and do not cause myotoxicity. Thus, the paper aims to discover potential SQS inhibitors from Traditional Chinese Medicine (TCM) by the combination of molecular modeling methods and biological assays. In this study, cynarin was selected as a potential SQS inhibitor candidate compound based on its pharmacophoric properties, molecular docking studies and molecular dynamics (MD) simulations...
April 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29680944/effect-of-terbinafine-on-the-biosynthetic-pathway-of-isoprenoid-compounds-in-carrot-suspension-cultured-cells
#4
Begoña Miras-Moreno, Lorena Almagro, María Angeles Pedreño, Ana Belén Sabater-Jara
Terbinafine induced a significant increase of squalene production. Terbinafine increased the expression levels of squalene synthase. Cyclodextrins did not work as elicitors due to the gene expression levels obtained. Plant sterols are essential components of membrane lipids, which contributing to their fluidity and permeability. Besides their cholesterol-lowering properties, they also have anti-inflammatory, antidiabetic and anticancer activities. Squalene, which is phytosterol precursor, is widely used in medicine, foods and cosmetics due to its anti-tumor, antioxidant and anti-aging activities...
April 21, 2018: Plant Cell Reports
https://www.readbyqxmd.com/read/29642531/a-possible-trifunctional-%C3%AE-carotene-synthase-gene-identified-in-the-draft-genome-of-aurantiochytrium-sp-strain-kh105
#5
Hiroaki Iwasaka, Ryo Koyanagi, Ryota Satoh, Akiko Nagano, Kenshi Watanabe, Kanako Hisata, Noriyuki Satoh, Tsunehiro Aki
Labyrinthulomycetes have been regarded as a promising industrial source of xanthophylls, including astaxanthin and canthaxanthin, polyunsaturated fatty acids such as docosahexaenoic acid and docosapentaenoic acid, ω-3 oils, and terpenic hydrocarbons, such as sterols and squalene. A Thraustochytrid, Aurantiochytrium sp. KH105 produces carotenoids, including astaxanthin, with strong antioxidant activity. To gain genomic insights into this capacity, we decoded its 97-Mbp genome and characterized genes for enzymes involved in carotenoid biosynthesis...
April 9, 2018: Genes
https://www.readbyqxmd.com/read/29552653/engineering-of-yarrowia-lipolytica-for-production-of-astaxanthin
#6
Kanchana Rueksomtawin Kildegaard, Belén Adiego-Pérez, David Doménech Belda, Jaspreet Kaur Khangura, Carina Holkenbrink, Irina Borodina
Astaxanthin is a red-colored carotenoid, used as food and feed additive. Astaxanthin is mainly produced by chemical synthesis, however, the process is expensive and synthetic astaxanthin is not approved for human consumption. In this study, we engineered the oleaginous yeast Yarrowia lipolytica for de novo production of astaxanthin by fermentation. First, we screened 12 different Y. lipolytica isolates for β-carotene production by introducing two genes for β-carotene biosynthesis: bi-functional phytoene synthase/lycopene cyclase ( crtYB ) and phytoene desaturase ( crtI ) from the red yeast Xanthophyllomyces dendrorhous ...
December 2017: Synthetic and Systems Biotechnology
https://www.readbyqxmd.com/read/29526355/enhancing-oleanolic-acid-production-in-engineered-saccharomyces-cerevisiae
#7
Yujia Zhao, Jingjing Fan, Chen Wang, Xudong Feng, Chun Li
Oleanolic acid is a plant-derived pentacyclic triterpenoid compound with various biological activities. Recently, biosynthesis of oleanolic acid in microbes has been demonstrated as a promising and green way, but the production is too low for industrialization. To improve oleanolic acid production, this study constructed a novel pathway for biosynthesis of oleanolic acid in Saccharomyces cerevisiae by improving the pairing efficiency between cytochrome P450 monooxygenase and reductase. Furthermore, to improve the transcriptional efficiency of heterologous genes, the cellular galactose regulatory network was reconstructed by knocking out galactose metabolic genes GAL80 and GAL1...
February 23, 2018: Bioresource Technology
https://www.readbyqxmd.com/read/29396745/high-level-recombinant-production-of-squalene-using-selected-saccharomyces-cerevisiae-strains
#8
Jong Yun Han, Sung Hwa Seo, Jae Myeong Song, Hongweon Lee, Eui-Sung Choi
For recombinant production of squalene, which is a triterpenoid compound with increasing industrial applications, in microorganisms generally recognized as safe, we screened Saccharomyces cerevisiae strains to determine their suitability. A strong strain dependence was observed in squalene productivity among Saccharomyces cerevisiae strains upon overexpression of genes important for isoprenoid biosynthesis. In particular, a high level of squalene production (400 ± 45 mg/L) was obtained in shake flasks with the Y2805 strain overexpressing genes encoding a bacterial farnesyl diphosphate synthase (ispA) and a truncated form of hydroxyl-3-methylglutaryl-CoA reductase (tHMG1)...
April 2018: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/29382150/cloning-expression-analysis-and-functional-characterization-of-squalene-synthase-sqs-from-tripterygium-wilfordii
#9
Bin Zhang, Yan Liu, Mengmeng Chen, Juntao Feng, Zhiqing Ma, Xing Zhang, Chuanshu Zhu
Celastrol is an active triterpenoid compound derived from Tripterygium wilfordii which is well-known as a traditional Chinese medicinal plant. Squalene synthase has a vital role in condensing two molecules of farnesyl diphosphate to form squalene, a key precursor of triterpenoid biosynthesis. In the present study, T. wilfordii squalene synthase (TwSQS) was cloned followed by prokaryotic expression and functional verification. The open reading frame cDNA of TwSQS was 1242 bp encoding 413 amino acids. Bioinformatic and phylogenetic analysis showed that TwSQS had high homology with other plant SQSs...
January 29, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29362090/nerolidol-production-in-agroinfiltrated-tobacco-impact-of-protein-stability-and-membrane-targeting-of-strawberry-fragraria-ananassa-nerolidol-synthase1
#10
Paola Andrade, David Manzano, Karla Ramirez-Estrada, Daniel Caudepon, Montserrat Arro, Albert Ferrer, Michael A Phillips
The sesquiterpene alcohol nerolidol, synthesized from farnesyl diphosphate (FDP), mediates plant-insect interactions across multiple trophic levels with major implications for pest management in agriculture. We compared nerolidol engineering strategies in tobacco using agroinfiltration to transiently express strawberry (Fragraria ananassa) linalool/nerolidol synthase (FaNES1) either at the endoplasmic reticulum (ER) or in the cytosol as a soluble protein. Using solid phase microextraction and gas chromatography-mass spectrometry (SPME-GCMS), we have determined that FaNES1 directed to the ER via fusion to the transmembrane domain of squalene synthase or hydroxymethylglutaryl - CoA reductase displayed significant improvements in terms of transcript levels, protein accumulation, and volatile production when compared to its cytosolic form...
February 2018: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/29355536/a-mathematical-model-of-the-mevalonate-cholesterol-biosynthesis-pathway
#11
Frances Pool, Richard Currie, Peter K Sweby, José Domingo Salazar, Marcus J Tindall
We formulate, parameterise and analyse a mathematical model of the mevalonate pathway, a key pathway in the synthesis of cholesterol. Of high clinical importance, the pathway incorporates rate limiting enzymatic reactions with multiple negative feedbacks. In this work we investigate the pathway dynamics and demonstrate that rate limiting steps and negative feedbacks within it act in concert to tightly regulate intracellular cholesterol levels. Formulated using the theory of nonlinear ordinary differential equations and parameterised in the context of a hepatocyte, the governing equations are analysed numerically and analytically...
April 14, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29340843/phytoene-production-utilizing-the-isoprenoid-biosynthesis-capacity-of-thermococcus-kodakarensis
#12
Tsubasa Fuke, Takaaki Sato, Savyasachee Jha, Myra L Tansengco, Haruyuki Atomi
Phytoene (C40H64) is an isoprenoid and a precursor of various carotenoids which are of industrial value. Archaea can be considered to exhibit a relatively large capacity to produce isoprenoids, as they are components of their membrane lipids. Here, we aimed to produce isoprenoids such as phytoene in the hyperthermophilic archaeon Thermococcus kodakarensis. T. kodakarensis harbors a prenyltransferase gene involved in the biosynthesis of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are precursors of squalene and phytoene, respectively...
January 16, 2018: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/29235288/-prokaryotic-expression-functional-identification-of-squalene-synthase-in-alisma-orientale-and-its-immunoassay-study
#13
Qing-Zhi Liu, Wei Gu, Qi-Nan Wu, Jian-Guo Chao, Xiao-Hua Sang, Qi Liu, Xiao-Hao Wang
Squalene synthase of Alisma orientale catalyzes farnesyl diphosphate (FPP) to form squalene, which is the key regulatory enzyme of the carbon source flow to protostane triterpenes biosynthesis. For further research on the function and expression of AoSS gene, the open reading frame (ORF) of squalene synthase gene (accession no. JX866770) from A. orientale was subcloned into a prokaryotic expression vector pCzn1 and induced the expression of AoSS gene in Escherichia coli BL21(Roseta). The fusion protein was mainly in the form of inclusion bodies and purified to obtain high purity protein...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29204767/heterologous-biosynthesis-of-triterpenoid-ambrein-in-engineered-escherichia-coli
#14
Di Ke, Qinggele Caiyin, Fanglong Zhao, Ting Liu, Wenyu Lu
OBJECTIVES: To genetically engineer Escherichia coli for the heterologous biosynthesis of triterpenoid, ambrein, the main bioactive component of ambergris, by constituting a novel squalene-derived ambrein biosynthetic pathway in E. coli. RESULTS: The ScERG9 gene encoding the squalene synthase (SS) was integrated into the E. coli genome to generate a squalene-producing strain that supplied the central precursor squalene for the formation of cyclic triterpenoids. The mutated squalene-hopene synthase (D377C SHC) and the tetraprenyl-β-curcumene cyclase (BmeTC) were co-expressed with SS to construct a novel ambrein biosynthetic pathway in E...
February 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29203557/a-single-oxidosqualene-cyclase-produces-the-seco-triterpenoid-%C3%AE-onocerin
#15
Aldo Almeida, Lemeng Dong, Bekzod Khakimov, Jean-Etienne Bassard, Tessa Moses, Frederic Lota, Alain Goossens, Giovanni Appendino, Søren Bak
8,14- seco -Triterpenoids are characterized by their unusual open C-ring. Their distribution in nature is rare and scattered in taxonomically unrelated plants. The 8,14- seco -triterpenoid α-onocerin is only known from the evolutionarily distant clubmoss genus Lycopodium and the leguminous genus Ononis , which makes the biosynthesis of this seco -triterpenoid intriguing from an evolutionary standpoint. In our experiments with Ononis spinosa, α-onocerin was detected only in the roots. Through transcriptome analysis of the roots, an oxidosqualene cyclase, OsONS1, was identified that produces α-onocerin from squalene-2,3;22,23-dioxide when transiently expressed in Nicotiana bethamiana In contrast, in Lycopodium clavatum , two sequential cyclases, LcLCC and LcLCD, are required to produce α-onocerin in the N...
February 2018: Plant Physiology
https://www.readbyqxmd.com/read/29142407/molecular-docking-analysis-of-phytic-acid-and-4-hydroxyisoleucine-as-cyclooxygenase-2-microsomal-prostaglandin-e-synthase-2-tyrosinase-human-neutrophil-elastase-matrix-metalloproteinase-2-and-9-xanthine-oxidase-squalene-synthase-nitric-oxide-synthase-human
#16
Radhakrishnan Narayanaswamy, Lam Kok Wai, Norhaizan Mohd Esa
Background: The phytoconstituents phytic acid and 4-hydroxyisoleucine have been reported to posses various biological properties. Objective: This prompted us to carry out the docking study on these two ligands (phytic acid & 4-hydroxyisoleucine) against eleven targeted enzymes. Materials and Methods: Phytic acid & 4-hydroxyisoleucine were evaluated on the docking behaviour of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-2 (mPGES-2), tyrosinase, human neutrophil elastase (HNE), matrix metalloproteinase (MMP 2 and 9), xanthine oxidase (XO), squalene synthase (SQS), nitric oxide synthase (NOS), human aldose reductase (HAR) and lipoxygenase (LOX) using Discovery Studio Version 3...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29122174/differential-gene-expression-profiling-analysis-in-pleurotus-ostreatus-during-interspecific-antagonistic-interactions-with-dichomitus-squalens-and-trametes-versicolor
#17
Zixuan Zhong, Liu Li, Peng Chang, Haiying Xie, Huiting Zhang, Yasuo Igarashi, Nannan Li, Feng Luo
This study provided analysis of differentially expressed genes (DEGs) in Pleurotus ostreatus under the interaction with Dichomitus squalens and Trametes versicolor, which is valuable for exploration on the fungal defence system against stressful condition caused by interspecific antagonistic interaction. Our result showed significant upregulation of abundant defence-related genes encoding laccase, manganese peroxidase, aldo-keto reductase, and glutathione S-transferase, which all play important roles in oxidative stress-resistant response...
December 2017: Fungal Biology
https://www.readbyqxmd.com/read/29107437/selenium-containing-analogues-of-wc-9-are-extremely-potent-inhibitors-of-trypanosoma-cruzi-proliferation
#18
María N Chao, Melissa Storey, Catherine Li, Maricel G Rodríguez, Florencia Di Salvo, Sergio H Szajnman, Silvia N J Moreno, Roberto Docampo, Juan B Rodriguez
The obligate intracellular parasite, Trypanosoma cruzi is the etiologic agent of Chagas disease or American trypanosomiasis, which is the most prevalent parasitic disease in the Americas. The present chemotherapy to control this illness is still deficient particularly in the chronic stage of the disease. The ergosterol biosynthesis pathway has received much attention as a molecular target for the development of new drugs for Chagas disease. Especially, inhibitors of the enzymatic activity of squalene synthase were shown to be effective compounds on T...
December 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29066794/enantiospecific-total-synthesis-of-the-squalene-synthase-inhibitors-cj-13-982-and-its-enantiomer-from-a-common-intermediate
#19
Dayna Sturgess, Zongjia Chen, Jonathan M White, Mark A Rizzacasa
The total syntheses of both the natural and unnatural enantiomers of the alkyl citrate natural product CJ-13,982 (1) from the common d-ribose-derived acid 6 are described.
February 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29056891/-polygala-tenuifolia-extract-inhibits-lipid-accumulation-in-3t3-l1-adipocytes-and-high-fat-diet-induced-obese-mouse-model-and-affects-hepatic-transcriptome-and-gut-microbiota-profiles
#20
Chun-Chung Wang, Jui-Hung Yen, Yi-Cheng Cheng, Chia-Yu Lin, Cheng-Ta Hsieh, Rung-Jiun Gau, Shu-Jiau Chiou, Hwan-You Chang
Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the effects of PTE on lipid accumulation...
2017: Food & Nutrition Research
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