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Biosynthesis

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https://www.readbyqxmd.com/read/28346939/a-b12-dependent-radical-sam-enzyme-involved-in-oxetanocin-a-biosynthesis
#1
Jennifer Bridwell-Rabb, Aoshu Zhong, He G Sun, Catherine L Drennan, Hung-Wen Liu
Oxetanocin A (OXT-A) is a potent antitumour, antiviral and antibacterial compound. Biosynthesis of OXT-A has been linked to a plasmid-borne Bacillus megaterium gene cluster that contains four genes: oxsA, oxsB, oxrA and oxrB. Here we show that both the oxsA and oxsB genes are required for the production of OXT-A. Biochemical analysis of the encoded proteins, a cobalamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohydrolase, OxsA, reveals that OXT-A is derived from a 2'-deoxyadenosine phosphate in an OxsB-catalysed ring contraction reaction initiated by hydrogen atom abstraction from C2'...
March 27, 2017: Nature
https://www.readbyqxmd.com/read/28346741/small-molecules-targeting-human-n-acetylmannosamine-kinase
#2
Stephan Hinderlich, Martin Neuenschwander, Paul-Robin Wratil, Andreas Oder, Michael Lisurek, Long D Nguyen, Jens Peter von Kries, Christian Hackenberger
N-Acetylmannosamine kinase (MNK) plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. For the search of effective inhibitors of MNK we applied high-throughput screening of drug-like small molecules. Applying different orthogonal assays for their validation we identified four potential MNK-specific inhibitors with IC50 values in the low micromolar range...
March 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28346710/the-arabidopsis-thiamin-deficient-mutant-pale-green1-lacks-thiamin-monophosphate-phosphatase-of-the-vitamin-b1-biosynthesis-pathway
#3
Wei-Yu Hsieh, Jo-Chien Liao, Hsin-Tzu Wang, Tzu-Huan Hung, Ching-Chih Tseng, Tsui-Yun Chung, Ming-Hsiun Hsieh
Thiamin diphosphate (TPP, vitamin B1) is an essential coenzyme present in all organisms. Animals obtain TPP from their diets, but plants synthesize TPP de novo. We isolated and characterized an Arabidopsis pale green1 (pale1) mutant that contained higher concentrations of thiamin monophosphate (TMP) and less thiamin and TPP than the wild type. Supplementation with thiamin, but not the thiazole and pyrimidine precursors, rescued the mutant phenotype, indicating that the pale1 mutant is a thiamin-deficient mutant...
March 27, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28346368/pathophysiological-significance-of-dermatan-sulfate-proteoglycans-revealed-by-human-genetic-disorders
#4
REVIEW
Shuji Mizumoto, Tomoki Kosho, Shuhei Yamada, Kazuyuki Sugahara
The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs) have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity...
March 27, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28346364/new-benzimidazole-1-2-4-triazole-hybrid-compounds-synthesis-anticandidal-activity-and-cytotoxicity-evaluation
#5
Hülya Karaca Gençer, Ulviye Acar Çevik, Serkan Levent, Begüm Nurpelin Sağlık, Büşra Korkut, Yusuf Özkay, Sinem Ilgın, Yusuf Öztürk
Owing to the growing need for antifungal agents, we synthesized a new series 2-((5-(4-(5-substituted-1H-benzimidazol-2-yl)phenyl)-4-substituted-4H-1,2,4-triazol-3-yl)thio)-1-(substitutedphenyl)ethan-1-one derivatives, which were tested against Candida species. The synthesized compounds were characterized and elucidated by FT-IR, ¹H-NMR, (13)C-NMR and HR-MS spectroscopies. The synthesized compounds were screened in vitro anticandidal activity against Candida species by broth microdiluation methods. In vitro cytotoxic effects of the final compounds were determined by MTT assay...
March 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28346351/in-vitro-and-in-vivo-studies-on-the-structural-organization-of-chs3-from-saccharomyces-cerevisiae
#6
Simon Gohlke, Subbaratnam Muthukrishnan, Hans Merzendorfer
Chitin biosynthesis in yeast is accomplished by three chitin synthases (Chs) termed Chs1, Chs2 and Chs3, of which the latter accounts for most of the chitin deposited within the cell wall. While the overall structures of Chs1 and Chs2 are similar to those of other chitin synthases from fungi and arthropods, Chs3 lacks some of the C-terminal transmembrane helices raising questions regarding its structure and topology. To fill this gap of knowledge, we performed bioinformatic analyses and protease protection assays that revealed significant information about the catalytic domain, the chitin-translocating channel and the interfacial helices in between...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346347/biosynthesis-of-%C3%AE-glucosidase-inhibitors-by-a-newly-isolated-bacterium-paenibacillus-sp-tku042-and-its-effect-on-reducing-plasma-glucose-in-a-mouse-model
#7
Van Bon Nguyen, Anh Dzung Nguyen, Yao-Haur Kuo, San-Lang Wang
Paenibacillus sp. TKU042, a bacterium isolated from Taiwanese soil, produced α-glucosidase inhibitors (aGIs) in the culture supernatant when commercial nutrient broth (NB) was used as the medium for fermentation. The supernatant of fermented NB (FNB) showed stronger inhibitory activities than acarbose, a commercial anti-diabetic drug. The IC50 and maximum α-glucosidase inhibitory activities (aGIA) of FNB and acarbose against α-glucosidase were 81 μg/mL, 92% and 1395 μg/mL, 63%, respectively. FNB was found to be strongly thermostable, retaining 95% of its relative activity, even after heating at 100 °C for 30 min...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#8
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346093/a-label-free-continuous-fluorescence-based-assay-for-monitoring-ornithine-decarboxylase-activity-with-a-synthetic-putrescine-receptor
#9
Mohamed Nilam, Philip Gribbon, Jeanette Reinshagen, Kathrin Cordts, Edzard Schwedhelm, Werner M Nau, Andreas Hennig
Polyamines play an important role in cell growth, differentiation, and cancer development, and the biosynthetic pathway of polyamines is established as a drug target for the treatment of parasitic diseases, neoplasia, and cancer chemoprevention. The key enzyme in polyamine biosynthesis is ornithine decarboxylase (ODC). We report herein an analytical method for the continuous fluorescence monitoring of ODC activity based on the supramolecular receptor cucurbit[6]uril (CB6) and the fluorescent dye trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide (DSMI)...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345864/triple-stage-mass-spectrometry-unravels-the-heterogeneity-of-an-endogenous-protein-complex
#10
Gili Ben-Nissan, Mikhail E Belov, David Morgenstern, Yishai Levin, Orly Dym, Galina Arkind, Carni Lipson, Alexander A Makarov, Michal Sharon
The way we perceive protein complexes is changing. What were once thought to be uniform entities may actually represent an ensemble of different assemblies with distinct functions and regulation. This increased complexity is enabled by the variety of protein diversification mechanisms that exist at every step of the protein biosynthesis pathway, such as alternative splicing and post transcriptional and translational modifications. The resulting variation in subunits can generate compositionally distinct protein assemblies...
March 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28345675/a-myb-transcription-factor-dcmyb6-is-involved-in-regulating-anthocyanin-biosynthesis-in-purple-carrot-taproots
#11
Zhi-Sheng Xu, Kai Feng, Feng Que, Feng Wang, Ai-Sheng Xiong
Carrots are widely grown and enjoyed around the world. Purple carrots accumulate rich anthocyanins in the taproots, while orange, yellow, and red carrots accumulate rich carotenoids in the taproots. Our previous studies indicated that variation in the activity of regulatory genes may be responsible for variations in anthocyanin production among various carrot cultivars. In this study, an R2R3-type MYB gene, designated as DcMYB6, was isolated from a purple carrot cultivar. In a phylogenetic analysis, DcMYB6 was grouped into an anthocyanin biosynthesis-related MYB clade...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345581/potential-of-biosynthesized-silver-nanoparticles-using-stenotrophomonas-sp-bhu-s7-mtcc-5978-for-management-of-soil-borne-and-foliar-phytopathogens
#12
Sandhya Mishra, Braj Raj Singh, Alim H Naqvi, H B Singh
Stenotrophomonas sp. is emerging as a popular microbe of global concern with various potential ecological roles. Biosynthesis of gold and silver nanoparticles (AgNPs) using this bacterial strain has shown promising applications in life sciences. However, there is no report on efficient agricultural applications of biosynthesized AgNPs using Stenotrophomonas sp. In this regard, successful biosynthesis of AgNPs using Stenotrophomonas sp. BHU-S7 (MTCC 5978) was monitored by Uv-visible spectrum showing surface plasmon resonance (SPR) peak at 440 nm...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345051/aflatoxin-free-transgenic-maize-using-host-induced-gene-silencing
#13
Dhiraj Thakare, Jianwei Zhang, Rod A Wing, Peter J Cotty, Monica A Schmidt
Aflatoxins, toxic secondary metabolites produced by some Aspergillus species, are a universal agricultural economic problem and a critical health issue. Despite decades of control efforts, aflatoxin contamination is responsible for a global loss of millions of tons of crops each year. We show that host-induced gene silencing is an effective method for eliminating this toxin in transgenic maize. We transformed maize plants with a kernel-specific RNA interference (RNAi) gene cassette targeting the aflC gene, which encodes an enzyme in the Aspergillus aflatoxin biosynthetic pathway...
March 2017: Science Advances
https://www.readbyqxmd.com/read/28344649/overexpression-of-a-domain-of-unknown-function-266-containing-protein-results-in-high-cellulose-content-reduced-recalcitrance-and-enhanced-plant-growth-in-the-bioenergy-crop-populus
#14
Yongil Yang, Chang Geun Yoo, Hao-Bo Guo, William Rottmann, Kimberly A Winkeler, Cassandra M Collins, Lee E Gunter, Sara S Jawdy, Xiaohan Yang, Hong Guo, Yunqiao Pu, Arthur J Ragauskas, Gerald A Tuskan, Jin-Gui Chen
BACKGROUND: Domain of Unknown Function 266 (DUF266) is a plant-specific domain. DUF266-containing proteins (DUF266 proteins) have been categorized as 'not classified glycosyltransferases (GTnc)' due to amino acid similarity with GTs. However, little is known about the function of DUF266 proteins. RESULTS: Phylogenetic analysis revealed that DUF266 proteins are only present in the land plants including moss and lycophyte. We report the functional characterization of one member of DUF266 proteins in Populus, PdDUF266A...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28344589/characterization-of-genes-encoding-key-enzymes-involved-in-anthocyanin-metabolism-of-kiwifruit-during-storage-period
#15
Boqiang Li, Yongxiu Xia, Yuying Wang, Guozheng Qin, Shiping Tian
'Hongyang' is a red fleshed kiwifruit with high anthocyanin content. In this study, we mainly investigated effects of different temperatures (25 and 0°C) on anthocyanin biosynthesis in harvested kiwifruit, and characterized the genes encoding key enzymes involved in anthocyanin metabolism, as well as evaluated the mode of the action, by which low temperature regulates anthocyanin accumulation in 'Hongyang' kiwifruit during storage period. The results showed that low temperature could effectively enhance the anthocyanin accumulation of kiwifruit in the end of storage period (90 days), which related to the increase in mRNA levels of ANS1, ANS2, DRF1, DRF2, and UGFT2...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28344586/comparative-transcriptome-reveals-benzenoid-biosynthesis-regulation-as-inducer-of-floral-scent-in-the-woody-plant-prunus-mume
#16
Kai Zhao, Weiru Yang, Yuzhen Zhou, Jie Zhang, Yushu Li, Sagheer Ahmad, Qixiang Zhang
Mei (Prunus mume) is a peculiar woody ornamental plant famous for its inviting fragrance in winter. However, in this valuable plant, the mechanism behind floral volatile development remains poorly defined. Therefore, to explore the floral scent formation, a comparative transcriptome was conducted in order to identify the global transcripts specifying flower buds and blooming flowers of P. mume. Differentially expressed genes were identified between the two different stages showing great discrepancy in floral volatile production...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28344584/lanthanum-affects-bell-pepper-seedling-quality-depending-on-the-genotype-and-time-of-exposure-by-differentially-modifying-plant-height-stem-diameter-and-concentrations-of-chlorophylls-sugars-amino-acids-and-proteins
#17
Atonaltzin García-Jiménez, Fernando C Gómez-Merino, Olga Tejeda-Sartorius, Libia I Trejo-Téllez
Lanthanum (La) is considered a beneficial element, capable of inducing hormesis. Hormesis is a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition. Herein we tested the effect of 0 and 10 μM La on growth and biomolecule concentrations of seedlings of four sweet bell pepper (Capsicum annuum L.) varieties, namely Sven, Sympathy, Yolo Wonder, and Zidenka. Seedling evaluations were performed 15 and 30 days after treatment applications (dat) under hydroponic greenhouse conditions...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28344500/plant-growth-and-diosgenin-enhancement-effect-of-silver-nanoparticles-in-fenugreek-trigonella-foenum-graecum-l
#18
B Jasim, Roshmi Thomas, Jyothis Mathew, E K Radhakrishnan
Various methods have been used to enhance production of chemically diverse phytochemicals especially medicinal natural products. With the advancement in nanotechnology, nanoparticles have been reported to have varying impact in plant growth and inducibility of phytochemical composition. Major objective of the study was to study the secondary metabolite modulatory effect of silver nanoparticles. In the current study, treatment of fenugreek seedlings with biosynthesized silver nanoparticles (Ag-NPs) was found to have significant impact on its growth parameters such as leaf number, root length, shoot length and wet weight...
March 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28344327/mevalonate-cascade-inhibition-by-simvastatin-induces-the-intrinsic-apoptosis-pathway-via-depletion-of-isoprenoids-in-tumor-cells
#19
Javad Alizadeh, Amir A Zeki, Nima Mirzaei, Sandipan Tewary, Adel Rezaei Moghadam, Aleksandra Glogowska, Pandian Nagakannan, Eftekhar Eftekharpour, Emilia Wiechec, Joseph W Gordon, Fred Y Xu, Jared T Field, Ken Y Yoneda, Nicholas J Kenyon, Mohammad Hashemi, Grant M Hatch, Sabine Hombach-Klonisch, Thomas Klonisch, Saeid Ghavami
The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344109/phylogenomic-proximity-and-metabolic-discrepancy-of-methanosarcina-mazei-go1-across-methanosarcinal-genomes
#20
M Bharathi, P Chellapandi
Methanosarcina mazei Go1 is a heterotrophic methanogenic archaean contributing a significant role in global methane cycling and biomethanation process. Phylogenomic relatedness and metabolic discrepancy of this genome were described herein by comparing its whole genome sequence, intergenomic distance, genome function, synteny homologs and origin of replication, and marker genes with very closely related genomes, Methanosarcina acetivorans and Methanosarcina barkeri. Phylogenomic analysis of this study revealed that genome functional feature and metabolic core of M...
March 23, 2017: Bio Systems
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