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https://www.readbyqxmd.com/read/28092657/lipid-production-in-yarrowia-lipolytica-is-maximized-by-engineering-cytosolic-redox-metabolism
#1
Kangjian Qiao, Thomas M Wasylenko, Kang Zhou, Peng Xu, Gregory Stephanopoulos
Microbial factories have been engineered to produce lipids from carbohydrate feedstocks for production of biofuels and oleochemicals. However, even the best yields obtained to date are insufficient for commercial lipid production. To maximize the capture of electrons generated from substrate catabolism and thus increase substrate-to-product yields, we engineered 13 strains of Yarrowia lipolytica with synthetic pathways converting glycolytic NADH into the lipid biosynthetic precursors NADPH or acetyl-CoA. A quantitative model was established and identified the yield of the lipid pathway as a crucial determinant of overall process yield...
January 16, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28091959/genetic-variation-in-mitochondrial-genes-of-the-tick-haemaphysalis-flava-collected-from-wild-hedgehogs-in-china
#2
Zhong-Bo Li, Tian-Yin Cheng, Xing-Li Xu, Lu-Lin Song, Guo-Hua Liu
The tick Haemaphysalis flava (Acari: Ixodidae) is an important ectoparasite, which causes direct damage to their hosts and also acts as a vector of various infectious disease agents in China. Despite its significance, the epidemiology, genetics and biology of H. flava has not been studied in detail. In the present study, the genetic variation in three mitochondrial (mt) DNA regions, namely cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 1 and 4 (nad1 and nad4), was examined in H. flava ticks collected from wild hedgehogs in China...
January 16, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28088640/bioethanol-production-from-cellulosic-hydrolysates-by-engineered-industrial-saccharomyces-cerevisiae
#3
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/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#4
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28087734/increased-mitophagy-in-the-skeletal-muscle-of-spinal-and-bulbar-muscular-atrophy-patients
#5
Doriana Borgia, Adriana Malena, Marco Spinazzi, Maria Andrea Desbats, Leonardo Salviati, Aaron P Russell, Giovanni Miotto, Laura Tosatto, Elena Pegoraro, Gianni Sorarù, Maria Pennuto, Lodovica Vergani
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and patients suffering from amyotrophic lateral sclerosis (ALS) and neurogenic atrophy. We detected atrophic fibers in the muscle of SBMA, ALS and neurogenic atrophy patients...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#6
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28086860/nicotiana-attenuata-data-hub-nadh-an-integrative-platform-for-exploring-genomic-transcriptomic-and-metabolomic-data-in-wild-tobacco
#7
Thomas Brockmöller, Zhihao Ling, Dapeng Li, Emmanuel Gaquerel, Ian T Baldwin, Shuqing Xu
BACKGROUND: Nicotiana attenuata (coyote tobacco) is an ecological model for studying plant-environment interactions and plant gene function under real-world conditions. During the last decade, large amounts of genomic, transcriptomic and metabolomic data have been generated with this plant which has provided new insights into how native plants interact with herbivores, pollinators and microbes. However, an integrative and open access platform that allows for the efficient mining of these -omics data remained unavailable until now...
January 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28072529/correlation-between-the-structure-and-catalytic-activity-of-cp-rh-substituted-bipyridine-complexes-for-nadh-regeneration
#8
Vinothkumar Ganesan, Dharmalingam Sivanesan, Sungho Yoon
A series of water-soluble half-sandwich [Cp*Rh(III)(N^N)Cl](+) (Cp* = pentamethylcyclopentadiene, N^N-substituted 2,2'-bipyridine) complexes containing electron-donating substituents around the 2,2'-bipyridyl ligand were synthesized and fully characterized for the regioselective reduction of nicotinamide coenzyme (NAD(+)). The influence of the positional effect of the substituents on the structural, electrochemical, and catalytic properties of the catalyst was systematically studied in detail. The catalytic efficiency of the substituted bipyridine Cp*Rh(III) complexes are inversely correlated with their redox potentials...
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
#9
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
https://www.readbyqxmd.com/read/28070695/barth-syndrome-connecting-cardiolipin-to-cardiomyopathy
#10
REVIEW
Nikita Ikon, Robert O Ryan
The Barth syndrome (BTHS) is caused by an inborn error of metabolism that manifests characteristic phenotypic features including altered mitochondrial membrane phospholipids, lactic acidosis, organic acid-uria, skeletal muscle weakness and cardiomyopathy. The underlying cause of BTHS has been definitively traced to mutations in the tafazzin (TAZ) gene locus on chromosome X. TAZ encodes a phospholipid transacylase that promotes cardiolipin acyl chain remodeling. Absence of tafazzin activity results in cardiolipin molecular species heterogeneity, increased levels of monolysocardiolipin and lower cardiolipin abundance...
January 9, 2017: Lipids
https://www.readbyqxmd.com/read/28070565/activation-of-respiratory-complex-i-from-escherichia-coli-studied-by-fluorescent-probes
#11
Nikolai Belevich, Galina Belevich, Zhiyong Chen, Subhash C Sinha, Marina Verkhovskaya
Respiratory Complex I from E. coli may exist in two interconverting forms: resting (R) and active (A). The R/A transition of purified, solubilized Complex I occurring upon turnover was studied employing two different fluorescent probes, Annine 6+, and NDB-acetogenin. NADH-induced fluorescent changes of both dyes bound to solubilized Complex I from E. coli were characterized as a function of the protein:dye ratio, temperature, ubiquinone redox state and the enzyme activity. Analysis of this data combined with time-resolved optical measurements of Complex I activity and spectral changes indicated two ubiquinone-binding sites; a possibility of reduction of the tightly-bound quinone in the resting state and reduction of the loosely-bound quinone in the active state is discussed...
January 2017: Heliyon
https://www.readbyqxmd.com/read/28068639/effects-of-argan-oil-on-the-mitochondrial-function-antioxidant-system-and-the-activity-of-nadph-generating-enzymes-in-acrylamide-treated-rat-brain
#12
Birsen Aydın
Argan oil (AO) is rich in minor compounds such as polyphenols and tocopherols which are powerful antioxidants. Acrylamide (ACR) has been classified as a neurotoxic agent in animals and humans. Mitochondrial oxidative stress and dysfunction is one of the most probable molecular mechanisms of neurodegenerative diseases. Female Sprague Dawley rats were exposed to ACR (50mg/kg i.p. three times a week), AO (6ml/kg,o.p, per day) or together for 30days. The activities of cytosolic enzymes such as xanthine oxidase (XO), glucose 6-phosphate dehydrogenase (G6PDH), glutathione-S-transferase (GST), mitochondrial oxidative stress, oxidative phosphorylation (OXPHOS) and tricarboxylic acid cycle (TCA) enzymes, mitochondrial metabolic function, adenosine triphosphate (ATP) level and acetylcholinesterase (AChE) activity were assessed in rat brain...
January 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28067952/plastomes-on-the-edge-the-evolutionary-breakdown-of-mycoheterotroph-plastid-genomes
#13
REVIEW
Sean W Graham, Vivienne K Y Lam, Vincent S F T Merckx
I. II. III. References SUMMARY: We examine recent evidence for ratchet-like genome degradation in mycoheterotrophs, plants that obtain nutrition from fungi. Initial loss of the NADH dehydrogenase-like (NDH) complex may often set off an irreversible evolutionary cascade of photosynthetic gene losses. Genes for plastid-encoded subunits of RNA polymerase and photosynthetic enzymes with secondary functions (Rubisco and ATP synthase) can persist initially, with nonsynchronous and quite broad windows in the relative timing of their loss...
January 9, 2017: New Phytologist
https://www.readbyqxmd.com/read/28067272/the-mechanism-of-catalysis-by-type-ii-nadh-quinone-oxidoreductases
#14
James N Blaza, Hannah R Bridges, David Aragão, Elyse A Dunn, Adam Heikal, Gregory M Cook, Yoshio Nakatani, Judy Hirst
Type II NADH:quinone oxidoreductase (NDH-2) is central to the respiratory chains of many organisms. It is not present in mammals so may be exploited as an antimicrobial drug target or used as a substitute for dysfunctional respiratory complex I in neuromuscular disorders. NDH-2 is a single-subunit monotopic membrane protein with just a flavin cofactor, yet no consensus exists on its mechanism. Here, we use steady-state and pre-steady-state kinetics combined with mutagenesis and structural studies to determine the mechanism of NDH-2 from Caldalkalibacillus thermarum...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063846/systematic-expression-analysis-of-mitochondrial-complex-i-identifies-ndufs1-as-a-biomarker-in-clear-cell-renal-cell-carcinoma
#15
Jörg Ellinger, Mirjam Poss, Maria Brüggemann, Arabella Gromes, Doris Schmidt, Nadja Ellinger, Yuri Tolkach, Dimo Dietrich, Glen Kristiansen, Stefan C Müller
INTRODUCTION: Mitochondrial dysfunction is common in cancer, and the mitochondrial electron transport chain is often affected in carcinogenesis. So far, little is known about the expression of the mitochondrial complex I (NADH:ubiquinone oxidoreductase) subunits in clear-cell renal-cell carcinoma (ccRCC). MATERIALS AND METHODS: An expression profile of the mitochondrial complex I subunits was determined using the NextBio database. Subsequently, the expression of selected subunits was experimentally validated on mRNA (quantitative real-time polymerase chain reaction) and protein (Western blot analysis, immunohistochemistry) level...
December 1, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28062838/enzymes-as-modular-catalysts-for-redox-half-reactions-in-h2-powered-chemical-synthesis-from-biology-to-technology
#16
REVIEW
Holly A Reeve, Philip A Ash, HyunSeo Park, Ailun Huang, Michalis Posidias, Chloe Tomlinson, Oliver Lenz, Kylie A Vincent
The present study considers the ways in which redox enzyme modules are coupled in living cells for linking reductive and oxidative half-reactions, and then reviews examples in which this concept can be exploited technologically in applications of coupled enzyme pairs. We discuss many examples in which enzymes are interfaced with electronically conductive particles to build up heterogeneous catalytic systems in an approach which could be termed synthetic biochemistry We focus on reactions involving the H(+)/H2 redox couple catalysed by NiFe hydrogenase moieties in conjunction with other biocatalysed reactions to assemble systems directed towards synthesis of specialised chemicals, chemical building blocks or bio-derived fuel molecules...
January 15, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28062235/new-approach-to-biosensing-of-co-enzyme-nicotinamide-adenine-dinucleotide-nadh-by-incorporation-of-neutral-red-in-aluminum-doped-nanostructured-zno-thin-films
#17
V T Fidal, T S Chandra
Biosensing of NADH on bare electrodes has drawbacks such as high over-potential and poisoning during the oxidation reaction. To overcome this challenge a different approach has been undertaken by incorporating neutral red (NR) in Al doped ZnO (AZO) thin films using one-pot chemical bath deposition (CBD). The surface morphology of the films was hexagonal nanorods along the c-axis, perpendicular to the substrate. The thickness of the thin films were ranging from 400 to 3000nm varying dependent on time of deposition (30 to 150min)...
January 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28061419/simultaneous-microbial-reduction-of-vanadium-v-and-chromium-vi-by-shewanella-loihica-pv-4
#18
Guangyu Wang, Baogang Zhang, Shuang Li, Meng Yang, Changcheng Yin
Toxic vanadium (V) and chromium (VI) often co-exist in wastewater from vanadium ore smelting and their reductions by bacterial strain Shewanella loihica PV-4 is realized simultaneously. After 27-d operation, 71.3% of V(V) and 91.2% of Cr(VI) were removed respectively, with citrate as organic carbon source. Enhancement of Cr(VI) bioreduction was observed with the suppressed V(V) reduction. V(IV) and Cr(III), the main reduction products, precipitated inside the organisms and attached on cell surfaces. Both membrane components containing cytochrome c and cytoplasmic fractions containing soluble proteins as well as NADH may contribute to these microbial reductions...
March 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28053088/identification-of-the-catalytic-ubiquinone-binding-site-of-vibrio-cholerae-sodium-dependent-nadh-dehydrogenase-a-novel-ubiquinone-binding-motif
#19
Karina Tuz, Chen Li, Xuan Fang, Daniel A Raba, Pingdong Liang, David D L Minh, Oscar Juarez
The sodium-dependent NADH dehydrogenase (Na+-NQR) is a key component of the respiratory chain of diverse prokaryotic species, including pathogenic bacteria. Na+-NQR uses the energy released by electron transfer between NADH and ubiquinone (UQ) to pump sodium, producing a gradient that sustains many essential homeostatic processes, as well as virulence factor secretion, and the elimination of drugs. The location of the UQ binding site has been controversial, with two main hypotheses that suggest that this site could be located in the cytosolic subunit A or in the membrane-bound subunit B...
January 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28052817/spectrophotometric-assay-for-sensitive-detection-of-glycerol-dehydratase-activity-using-aldehyde-dehydrogenase
#20
Eul-Soo Park, Sunghoon Park, Jong-Shik Shin
Glycerol dehydratase (GDHt) is a pivotal enzyme for fermentative utilization of glycerol by catalyzing radical-mediated conversion of glycerol into 3-hydroxypropionaldehyde (3-HPA). Precise and sensitive monitoring of cellular GDHt activity during the fermentation process is a prerequisite for reliable metabolic analysis to afford efficient cellular engineering and process optimization. Here we report a new spectrophotometric assay for the sensitive measurement of the GDHt activity with a sub-nanomolar limit of detection (LOD)...
January 2, 2017: Journal of Bioscience and Bioengineering
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