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https://www.readbyqxmd.com/read/28088640/bioethanol-production-from-cellulosic-hydrolysates-by-engineered-industrial-saccharomyces-cerevisiae
#1
Ye-Gi Lee, Yong-Su Jin, Young-Lok Cha, Jin-Ho Seo
Even though industrial yeast strains exhibit numerous advantageous traits for the production of bioethanol, their genetic manipulation has been limited. This study demonstrates that an industrial polyploidy Saccharomyces cerevisiae JHS200 can be engineered through Cas9 (CRISPR associated protein 9)-based genome editing. Specifically, we generated auxotrophic mutants and introduced a xylose metabolic pathway into the auxotrophic mutants. As expected, the engineered strain (JX123) enhanced ethanol production from cellulosic hydrolysates as compared to other engineered haploid strains...
December 18, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/28087410/repair-of-8-oxog-a-mismatches-by-the-mutyh-glycosylase-mechanism-metals-medicine
#2
REVIEW
Douglas M Banda, Nicole N Nuñez, Michael A Burnside, Katie M Bradshaw, Sheila S David
Reactive oxygen and nitrogen species (RONS) may infringe on the passing of pristine genetic information by inducing DNA inter- and intra-strand crosslinks, protein-DNA crosslinks, and chemical alterations to the sugar or base moieties of DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most prevalent DNA lesions formed by RONS and is repaired through the base excision repair (BER) pathway involving the DNA repair glycosylases OGG1 and MUTYH in eukaryotes. MUTYH removes adenine (A) from 8-oxoG:A mispairs, thus mitigating the potential of G:C to T:A transversion mutations from occurring in the genome...
January 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28087279/alpha-2-macroglobulin-and-heparin-cofactor-ii-and-the-vulnerability-of-carotid-atherosclerotic-plaques-an-itraq-based-analysis
#3
Jinmao Li, Xi Liu, Ying Xiang, Xueying Ding, Teng Wang, Ying Liu, Maojia Yin, Changhong Tan, Fen Deng, Lifen Chen
Rupture of carotid atherosclerotic plaque may cause stroke, while few biomarker in clinic can evaluate carotid plaque vulnerability. In this study, we divided the recruited participants into no plaque, stable plaque, and vulnerable plaque group according to carotid ultrasonography, and screened the differentially expressed proteins in plasma of these participants using isobaric tags for relative and absolute quantitation labeling coupled with liquid chromatography-tandem mass spectrometry. 28 proteins were identified differentially expressed, among which alpha-2-macroglobulin (α2M) and heparin cofactor II (HCII) were found to be at hub position in the interactions of these proteins by STRING analysis and were selected for enzyme-linked immunosorbent assay measurement to assess their relevance with carotid plaques vulnerability and diagnostic efficiency...
January 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28087247/activity-of-von-willebrand-factor-and-levels-of-vwf-cleaving-protease-adamts13-in-preterm-and-full-term-neonates
#4
T Strauss, N Elisha, B Ravid, N Rosenberg, A Lubetsky, S Levy-Mendelovich, I Morag, U Nowak Göttl, G Kenet
Von Willebrand Factor (VWF) has a central role in primary hemostasis. Its biological activity is related to the size of VWF multimers, spontaneously binding to platelets and inducing circulating microthrombi formation. This process is down-regulated by the VWF cleaving protease ADAMTS13 (A Disintegrin and Metalloprotease with ThromboSpondin motif). To date, information regarding the levels of ADAMTS13 in neonates and preterm infants is scarce. Our aim was to study ADAMTS13, VWF antigen (Ag) and Ristocetin cofactor (RiCof) activity in neonates and evaluate potential correlations with perinatal complications...
December 29, 2016: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28080030/chemoselective-enzymatic-c-h-bond-amination-catalyzed-by-a-cytochrome-p450-containing-an-ir-me-pix-cofactor
#5
Pawel Dydio, Hanna M Key, Hiroki Hayashi, Douglas S Clark, John F Hartwig
Cytochrome P450 enzymes have been engineered to catalyze abiological C-H bond amination reactions, but this abiological process is limited by the low chemoselectivity for the amination of C-H bonds over competing reduction of the substrate to a sulfonamide. Here we report that P450s derived from a thermophilic organism and containing an iridium porphyrin cofactor (Ir(Me)-PIX) in place of the heme catalyze C-H bond amination reactions with high chemoselectivity for intramolecular insertion of the resulting nitrenes into C-H bonds over reduction of the azide to the sulfonamide and with broader substrate scope than that of enzymes containing iron porphyrins...
January 12, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28079218/zinc-ion-induced-conformational-changes-in-new-delphi-metallo-%C3%AE-lactamase-1-probed-by-molecular-dynamics-simulations-and-umbrella-sampling
#6
Jianzhong Chen, Jinan Wang, Weiliang Zhu
The hydrolysis of a β-lactam core ring caused by new Delphi metallo-β-lactamase 1 (NDM-1) with the help of two zinc cofactors induces significant resistance toward β-lactam antibiotics. Molecular dynamics (MD) simulations and the umbrella sampling method are integrated to study the conformational change mechanism of NDM-1 mediated by zinc ion binding. The statistical analyses of interaction contacts of the antibiotic ampicillin (AMP) with residues based on MD trajectories suggest that two Zn ions are essential for maintaining the binding of AMP with NDM-1...
January 12, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28079055/intestinal-microbiota-as-a-tetrahydrobiopterin-exogenous-source-in-hph-1-mice
#7
Jaques Belik, Yulia Shifrin, Erland Arning, Teodoro Bottiglieri, Jingyi Pan, Michelle C Daigneault, Emma Allen-Vercoe
Tetrahydrobiopterin (BH4) is a cofactor of a number of regulatory enzymes. Although there are no known BH4 exogenous sources, the tissue content of this biopterin increases with age in GTP cyclohydrolase 1-deficient hyperphenylalaninemia-1 (hph-1) mice. Since certain bacteria are known to generate BH4, we hypothesize that generation of this biopterin by the intestinal microbiota contributes to its tissue increase in hph-1 adult mice. The goal of this study was to comparatively evaluate hph-1 mice and wild-type C57Bl/6 controls for the presence of intestinal BH4-producing bacteria...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078904/malonyl-coa-pathway-a-promising-route-for-3-hydroxypropionate-biosynthesis
#8
Changshui Liu, Yamei Ding, Mo Xian, Min Liu, Huizhou Liu, Qingjun Ma, Guang Zhao
3-Hydroxypropionate (3HP) is an attractive platform chemical, serving as a precursor to a variety of commodity chemicals like acrylate and acrylamide, as well as a monomer of a biodegradable plastic. To establish a sustainable way to produce these commercially important chemicals and materials, fermentative production of 3HP is widely investigated in recent years. It is reported that 3HP can be produced from several intermediates, such as glycerol, malonyl-CoA, and β-alanine. Among all these biosynthetic routes, the malonyl-CoA pathway has some distinct advantages, including a broad feedstock spectrum, thermodynamic feasibility, and redox neutrality...
January 12, 2017: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/28078823/hippo-vs-crab-tissue-specific-functions-of-the-mammalian-hippo-pathway
#9
REVIEW
Miki Nishio, Tomohiko Maehama, Hiroki Goto, Keisuke Nakatani, Wakako Kato, Hirofumi Omori, Yosuke Miyachi, Hideru Togashi, Yohei Shimono, Akira Suzuki
The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28077763/a-simplified-mathematical-model-of-directional-dna-site-specific-recombination-by-serine-integrases
#10
Alexandra Pokhilko, Jia Zhao, W Marshall Stark, Sean D Colloms, Oliver Ebenhöh
Serine integrases catalyse site-specific recombination to integrate and excise bacteriophage genomes into and out of their host's genome. These enzymes exhibit remarkable directionality; in the presence of the integrase alone, recombination between attP and attB DNA sites is efficient and irreversible, giving attL and attR products which do not recombine further. However, in the presence of the bacteriophage-encoded recombination directionality factor (RDF), integrase efficiently promotes recombination between attL and attR to re-form attP and attB The DNA substrates and products of both reactions are approximately isoenergetic, and no cofactors (such as adenosine triphosphate) are required for recombination...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28077290/hidden-symmetries-of-dna-molecule
#11
Alexander A Tulub, Vassily E Stefanov
Despite the fact that DNA molecule is studied up and down, we know very little about the role of DNA triplets in coding amino acids and stop-codons. The paper aims to fill this gap through attracting spintronic ideas and carrying out QM/MM computations on a full-turn DNA fragment. The computations reveal two hidden symmetries: the spin splitting (the Rashba effect), confined within each triplet, and the quantum "phase" link between the triplet nature (in total, 64 triplets) and the corresponding amino acid and three stop-codons...
January 7, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28076815/fluorescent-labeling-preserving-ocp-photoactivity-reveals-its-reorganization-during-the-photocycle
#12
Eugene G Maksimov, Nikolai N Sluchanko, Kirill S Mironov, Evgeny A Shirshin, Konstantin E Klementiev, Georgy V Tsoraev, Marcus Moldenhauer, Thomas Friedrich, Dmitry A Los, Suleyman I Allakhverdiev, Vladimir Z Paschenko, Andrei B Rubin
Orange carotenoid protein (OCP), responsible for the photoprotection of the cyanobacterial photosynthetic apparatus under excessive light conditions, undergoes significant rearrangements upon photoconversion and transits from the stable orange to the signaling red state. This is thought to involve a 12-Å translocation of the carotenoid cofactor and separation of the N- and C-terminal protein domains. Despite clear recent progress, the detailed mechanism of the OCP photoconversion and associated photoprotection remains elusive...
January 10, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28076781/crtc1-nuclear-translocation-following-learning-modulates-memory-strength-via-exchange-of-chromatin-remodeling-complexes-on-the-fgf1-gene
#13
Shusaku Uchida, Brett J W Teubner, Charles Hevi, Kumiko Hara, Ayumi Kobayashi, Rutu M Dave, Tatsushi Shintaku, Pattaporn Jaikhan, Hirotaka Yamagata, Takayoshi Suzuki, Yoshifumi Watanabe, Stanislav S Zakharenko, Gleb P Shumyatsky
Memory is formed by synapse-to-nucleus communication that leads to regulation of gene transcription, but the identity and organizational logic of signaling pathways involved in this communication remain unclear. Here we find that the transcription cofactor CRTC1 is a critical determinant of sustained gene transcription and memory strength in the hippocampus. Following associative learning, synaptically localized CRTC1 is translocated to the nucleus and regulates Fgf1b transcription in an activity-dependent manner...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076332/lysosomal-acid-phosphatase-2-is-an-unfavorable-prognostic-factor-but-is-associated-with-better-survival-in-stage-ii-colorectal-cancer-patients-receiving-chemotherapy
#14
Yu-Chieh Lee, Chia-Yu Su, Yuan-Feng Lin, Chun-Mao Lin, Chih-Yeu Fang, Yen-Kuang Lin, Michael Hsiao, Chi-Long Chen
Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression (p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28075562/evidence-for-a-di-%C3%A2%C2%B5-oxo-diamond-core-in-the-mn-iv-fe-iv-activation-intermediate-of-ribonucleotide-reductase-from-chlamydia-trachomatis
#15
Ryan J Martinie, Elizabeth J Blaesi, Carsten Krebs, J Martin Bollinger, Alexey Silakov, Christopher J Pollock
High-valent iron and manganese complexes effect some of the most challenging biochemical reactions known, including hydrocarbon and water oxidations associated with the global carbon cycle and oxygenic photosynthesis, respectively. Their extreme reactivity presents an impediment to structural characterization, but their biological importance and potential chemical utility have, nevertheless, motivated extensive efforts toward that end. Several such intermediates accumulate during activation of class I ribonucleotide reductase (RNR) β subunits, which self-assemble dimetal cofactors with stable one-electron oxidants that serve to initiate the enzyme's free-radical mechanism...
January 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28074650/revisiting-the-val-ile-mutation-in-mammalian-and-bacterial-no-synthases-a-spectroscopic-and-kinetic-study
#16
Marine Weisslocker-Schaetzel, Mehdi Lembrouk, Jerome Santolini, Pierre Dorlet
Nitric oxide (NO) is produced in mammals by the nitric oxide synthase (NOS) isoforms at a catalytic site comprising a heme associated with a biopterin cofactor. Through genome sequencing, proteins with high homology to the oxygenase domain of NOSs have been identified, in particular in bacteria. The active site is highly conserved except for a valine residue in the distal pocket that is replaced by an isoleucine in bacteria. This switch was previously reported to influence the kinetics of the reaction. We have used the V346I mutant of the mouse inducible NOS (iNOS) as well as the I224V mutant of the NOS from Bacillus subtilis (bsNOS) to study their spectroscopic signatures in solution and look for potential structural differences compared to their respective wild types...
January 11, 2017: Biochemistry
https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#17
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28073635/pcna-dependent-cellular-activities-tolerate-dramatic-perturbations-in-pcna-client-interactions
#18
Rosemary H C Wilson, Antonio J Biasutto, Lihao Wang, Roman Fischer, Emma L Baple, Andrew H Crosby, Erika J Mancini, Catherine M Green
Proliferating cell nuclear antigen (PCNA) is an essential cofactor for DNA replication and repair, recruiting multiple proteins to their sites of action. We examined the effects of the PCNA(S228I) mutation that causes PCNA-associated DNA repair disorder (PARD). Cells from individuals affected by PARD are sensitive to the PCNA inhibitors T3 and T2AA, showing that the S228I mutation has consequences for undamaged cells. Analysis of the binding between PCNA and PCNA-interacting proteins (PIPs) shows that the S228I change dramatically impairs the majority of these interactions, including that of Cdt1, DNMT1, PolD3(p66) and PolD4(p12)...
December 31, 2016: DNA Repair
https://www.readbyqxmd.com/read/28071903/revisiting-the-m%C3%A3-ssbauer-isomer-shifts-of-the-femoco-cluster-of-nitrogenase-and-the-cofactor-charge
#19
Ragnar Bjornsson, Frank Neese, Serena DeBeer
Despite decades of research, the structure-activity relationship of nitrogenase is still not understood. Only recently was the full molecular structure of the FeMo cofactor (FeMoco) revealed, but the charge and metal oxidation states of FeMoco have been controversial. With the recent identification of the interstitial atom as a carbide and the more recent revised oxidation-state assignment of the molybdenum atom as Mo(III), here we revisit the Mössbauer properties of FeMoco. By a detailed error analysis of density functional theory-computed isomer shifts and computing isomer shifts relative to the P-cluster, we find that only the charge of [MoFe7S9C](1-) fits the experimental data...
January 10, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28070721/enhanced-xylose-fermentation-by-engineered-yeast-expressing-nadh-oxidase-through-high-cell-density-inoculums
#20
Guo-Chang Zhang, Timothy L Turner, Yong-Su Jin
Accumulation of reduced byproducts such as glycerol and xylitol during xylose fermentation by engineered Saccharomyces cerevisiae hampers the economic production of biofuels and chemicals from cellulosic hydrolysates. In particular, engineered S. cerevisiae expressing NADPH-linked xylose reductase (XR) and NAD(+)-linked xylitol dehydrogenase (XDH) produces substantial amounts of the reduced byproducts under anaerobic conditions due to the cofactor difference of XR and XDH. While the additional expression of a water-forming NADH oxidase (NoxE) from Lactococcus lactis in engineered S...
January 9, 2017: Journal of Industrial Microbiology & Biotechnology
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