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https://www.readbyqxmd.com/read/27913830/genome-scale-modeling-of-thermophilic-microorganisms
#1
Sanjeev Dahal, Suresh Poudel, R Adam Thompson
Thermophilic microorganisms are of increasing interest for many industries as their enzymes and metabolisms are highly efficient at elevated temperatures. However, their metabolic processes are often largely different from their mesophilic counterparts. These differences can lead to metabolic engineering strategies that are doomed to fail. Genome-scale metabolic modeling is an effective and highly utilized way to investigate cellular phenotypes and to test metabolic engineering strategies. In this review we chronicle a number of thermophilic organisms that have recently been studied with genome-scale models...
December 3, 2016: Advances in Biochemical Engineering/biotechnology
https://www.readbyqxmd.com/read/27911809/unique-attributes-of-cyanobacterial-metabolism-revealed-by-improved-genome-scale-metabolic-modeling-and-essential-gene-analysis
#2
Jared T Broddrick, Benjamin E Rubin, David G Welkie, Niu Du, Nathan Mih, Spencer Diamond, Jenny J Lee, Susan S Golden, Bernhard O Palsson
The model cyanobacterium, Synechococcus elongatus PCC 7942, is a genetically tractable obligate phototroph that is being developed for the bioproduction of high-value chemicals. Genome-scale models (GEMs) have been successfully used to assess and engineer cellular metabolism; however, GEMs of phototrophic metabolism have been limited by the lack of experimental datasets for model validation and the challenges of incorporating photon uptake. Here, we develop a GEM of metabolism in S. elongatus using random barcode transposon site sequencing (RB-TnSeq) essential gene and physiological data specific to photoautotrophic metabolism...
December 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27909940/enhancement-of-rapamycin-production-by-metabolic-engineering-in-streptomyces-hygroscopicus-based-on-genome-scale-metabolic-model
#3
Lanqing Dang, Jiao Liu, Cheng Wang, Huanhuan Liu, Jianping Wen
Rapamycin, as a macrocyclic polyketide with immunosuppressive, antifungal, and anti-tumor activity produced by Streptomyces hygroscopicus, is receiving considerable attention for its significant contribution in medical field. However, the production capacity of the wild strain is very low. Hereby, a computational guided engineering approach was proposed to improve the capability of rapamycin production. First, a genome-scale metabolic model of Streptomyces hygroscopicus ATCC 29253 was constructed based on its annotated genome and biochemical information...
December 1, 2016: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27909649/in-silico-profiling-of-cell-growth-and-succinate-production-in-escherichia-coli-nzn111
#4
Xingxing Jian, Ningchuan Li, Cheng Zhang, Qiang Hua
BACKGROUND: Succinic acid is a valuable product due to its wide-ranging utilities. To improve succinate production and reduce by-products formation, Escherichia coli NZN111 was constructed by insertional inactivation of lactate dehydrogenase (LDH) and pyruvate formate lyase (PFL) encoded by the genes ldhA and pflB, respectively. However, this double-deletion mutant is incapable of anaerobically growing on glucose in rich or minimal medium even with acetate supplementation. A widespread hold view is that the inactivation of NADH-dependent LDH limits the regeneration of NAD(+) and consequently disables proper growth under anaerobic conditions...
2016: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/27899536/a-comprehensively-curated-genome-scale-two-cell-model-for-the-cyanobacterium-anabaena-sp-pcc-7120
#5
David Malatinszky, Ralf Steuer, Patrik R Jones
Anabaena sp. PCC 7120 is a nitrogen-fixing filamentous cyanobacterium. Under nitrogen limiting conditions, a fraction of the vegetative cells in each filament terminally differentiate to non-growing heterocysts. Heterocysts are metabolically and structurally specialized to enable O2-sensitive nitrogen fixation. The functionality of the filament, as an association of vegetative cells and heterocysts, is postulated to depend on metabolic exchange of electrons, carbon and fixed nitrogen. In the present work, we compile and evaluate a comprehensive curated stoichiometric model of this two-cell system, with the objective function based on the growth of the filament under diazotrophic conditions...
November 29, 2016: Plant Physiology
https://www.readbyqxmd.com/read/27897000/identifying-cancer-specific-metabolic-signatures-using-constraint-based-models
#6
A Schultz, S Mehta, C W Hu, F W Hoff, T M Horton, S M Kornblau, A A Qutub
Cancer metabolism differs remarkably from the metabolism of healthy surrounding tissues, and it is extremely heterogeneous across cancer types. While these metabolic differences provide promising avenues for cancer treatments, much work remains to be done in understanding how metabolism is rewired in malignant tissues. To that end, constraint-based models provide a powerful computational tool for the study of metabolism at the genome scale. To generate meaningful predictions, however, these generalized human models must first be tailored for specific cell or tissue sub-types...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27893703/generation-of-genome-scale-metabolic-reconstructions-for-773-members-of-the-human-gut-microbiota
#7
Stefanía Magnúsdóttir, Almut Heinken, Laura Kutt, Dmitry A Ravcheev, Eugen Bauer, Alberto Noronha, Kacy Greenhalgh, Christian Jäger, Joanna Baginska, Paul Wilmes, Ronan M T Fleming, Ines Thiele
Genome-scale metabolic models derived from human gut metagenomic data can be used as a framework to elucidate how microbial communities modulate human metabolism and health. We present AGORA (assembly of gut organisms through reconstruction and analysis), a resource of genome-scale metabolic reconstructions semi-automatically generated for 773 human gut bacteria. Using this resource, we identified a defined growth medium for Bacteroides caccae ATCC 34185. We also showed that interactions among modeled species depend on both the metabolic potential of each species and the nutrients available...
November 28, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27883890/a-consensus-genome-scale-reconstruction-of-chinese-hamster-ovary-cell-metabolism
#8
Hooman Hefzi, Kok Siong Ang, Michael Hanscho, Aarash Bordbar, David Ruckerbauer, Meiyappan Lakshmanan, Camila A Orellana, Deniz Baycin-Hizal, Yingxiang Huang, Daniel Ley, Veronica S Martinez, Sarantos Kyriakopoulos, Natalia E Jiménez, Daniel C Zielinski, Lake-Ee Quek, Tune Wulff, Johnny Arnsdorf, Shangzhong Li, Jae Seong Lee, Giuseppe Paglia, Nicolas Loira, Philipp N Spahn, Lasse E Pedersen, Jahir M Gutierrez, Zachary A King, Anne Mathilde Lund, Harish Nagarajan, Alex Thomas, Alyaa M Abdel-Haleem, Juergen Zanghellini, Helene F Kildegaard, Bjørn G Voldborg, Ziomara P Gerdtzen, Michael J Betenbaugh, Bernhard O Palsson, Mikael R Andersen, Lars K Nielsen, Nicole Borth, Dong-Yup Lee, Nathan E Lewis
Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell-line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells provide the biochemical basis of growth and recombinant protein production...
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27883886/cho-cells-can-make-more-protein
#9
Sarah W Harcum, Kelvin H Lee
A new comprehensive genome-scale metabolic model of Chinese hamster ovary cells identifies pathways for improving biopharmaceutical protein production.
November 23, 2016: Cell Systems
https://www.readbyqxmd.com/read/27879333/the-genome-wide-interaction-network-of-nutrient-stress-genes-in-escherichia-coli
#10
Jean-Philippe Côté, Shawn French, Sebastian S Gehrke, Craig R MacNair, Chand S Mangat, Amrita Bharat, Eric D Brown
: Conventional efforts to describe essential genes in bacteria have typically emphasized nutrient-rich growth conditions. Of note, however, are the set of genes that become essential when bacteria are grown under nutrient stress. For example, more than 100 genes become indispensable when the model bacterium Escherichia coli is grown on nutrient-limited media, and many of these nutrient stress genes have also been shown to be important for the growth of various bacterial pathogens in vivo To better understand the genetic network that underpins nutrient stress in E...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27879330/quantitative-transcriptomics-reveals-the-growth-and-nutrient-dependent-response-of-a-streamlined-marine-methylotroph-to-methanol-and-naturally-occurring-dissolved-organic-matter
#11
Scott M Gifford, Jamie W Becker, Oscar A Sosa, Daniel J Repeta, Edward F DeLong
The members of the OM43 clade of Betaproteobacteria are abundant coastal methylotrophs with a range of carbon-utilizing capabilities. However, their underlying transcriptional and metabolic responses to shifting conditions or different carbon substrates remain poorly understood. We examined the transcriptional dynamics of OM43 isolate NB0046 subjected to various inorganic nutrient, vitamin, and carbon substrate regimes over different growth phases to (i) develop a quantitative model of its mRNA content; (ii) identify transcriptional markers of physiological activity, nutritional state, and carbon and energy utilization; and (iii) identify pathways involved in methanol or naturally occurring dissolved organic matter (DOM) metabolism...
November 22, 2016: MBio
https://www.readbyqxmd.com/read/27870845/identification-of-conserved-moieties-in-metabolic-networks-by-graph-theoretical-analysis-of-atom-transition-networks
#12
Hulda S Haraldsdóttir, Ronan M T Fleming
Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27868089/adaptive-evolution-of-phosphorus-metabolism-in-prochlorococcus
#13
John R Casey, Adil Mardinoglu, Jens Nielsen, David M Karl
Inorganic phosphorus is scarce in the eastern Mediterranean Sea, where the high-light-adapted ecotype HLI of the marine picocyanobacterium Prochlorococcus marinus thrives. Physiological and regulatory control of phosphorus acquisition and partitioning has been observed in HLI both in culture and in the field; however, the optimization of phosphorus metabolism and associated gains for its phosphorus-limited-growth (PLG) phenotype have not been studied. Here, we reconstructed a genome-scale metabolic network of the HLI axenic strain MED4 (iJC568), consisting of 568 metabolic genes in relation to 794 reactions involving 680 metabolites distributed in 6 subcellular locations...
November 2016: MSystems
https://www.readbyqxmd.com/read/27864543/long-non-coding-rnas-a-novel-paradigm-for-toxicology
#14
REVIEW
Joseph L Dempsey, Julia Yue Cui
Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and are transcribed from the mammalian genome in a tissue-specific and developmentally regulated pattern. There is growing recognition that lncRNAs are novel biomarkers and/or key regulators of toxicological responses in humans and animal models. Lacking protein-coding capacity, the numerous types of lncRNAs possess a myriad of transcriptional regulatory functions that include cis and trans gene expression, transcription factor activity, chromatin remodeling, imprinting, and enhancer up-regulation...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/27857205/principles-of-proteome-allocation-are-revealed-using-proteomic-data-and-genome-scale-models
#15
Laurence Yang, James T Yurkovich, Colton J Lloyd, Ali Ebrahim, Michael A Saunders, Bernhard O Palsson
Integrating omics data to refine or make context-specific models is an active field of constraint-based modeling. Proteomics now cover over 95% of the Escherichia coli proteome by mass. Genome-scale models of Metabolism and macromolecular Expression (ME) compute proteome allocation linked to metabolism and fitness. Using proteomics data, we formulated allocation constraints for key proteome sectors in the ME model. The resulting calibrated model effectively computed the "generalist" (wild-type) E. coli proteome and phenotype across diverse growth environments...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27842992/systematic-review-and-meta-analysis-of-genetic-association-studies-in-idiopathic-recurrent-spontaneous-abortion
#16
Nina Pereza, Saša Ostojić, Miljenko Kapović, Borut Peterlin
OBJECTIVES: 1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable...
November 11, 2016: Fertility and Sterility
https://www.readbyqxmd.com/read/27825806/genome-scale-metabolic-modeling-of-cancer
#17
Avlant Nilsson, Jens Nielsen
Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome...
November 4, 2016: Metabolic Engineering
https://www.readbyqxmd.com/read/27824148/can-microbes-compete-with-cows-for-sustainable-protein-production-a-feasibility-study-on-high-quality-protein
#18
Mike Vestergaard, Siu Hung Joshua Chan, Peter Ruhdal Jensen
An increasing population and their increased demand for high-protein diets will require dramatic changes in the food industry, as limited resources and environmental issues will make animal derived foods and proteins, gradually more unsustainable to produce. To explore alternatives to animal derived proteins, an economic model was built around the genome-scale metabolic network of E. coli to study the feasibility of recombinant protein production as a food source. Using a novel model, we predicted which microbial production strategies are optimal for economic return, by capturing the tradeoff between the market prices of substrates, product output and the efficiency of microbial production...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822554/farnesoid-x-receptor-signaling-shapes-the-gut-microbiota-and-controls-hepatic-lipid-metabolism
#19
Limin Zhang, Cen Xie, Robert G Nichols, Siu H J Chan, Changtao Jiang, Ruixin Hao, Philip B Smith, Jingwei Cai, Margaret N Simons, Emmanuel Hatzakis, Costas D Maranas, Frank J Gonzalez, Andrew D Patterson
The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism...
September 2016: MSystems
https://www.readbyqxmd.com/read/27819051/serine-one-carbon-catabolism-with-formate-overflow
#20
Johannes Meiser, Sergey Tumanov, Oliver Maddocks, Christiaan Fred Labuschagne, Dimitris Athineos, Niels Van Den Broek, Gillian M Mackay, Eyal Gottlieb, Karen Blyth, Karen Vousden, Jurre J Kamphorst, Alexei Vazquez
Serine catabolism to glycine and a one-carbon unit has been linked to the anabolic requirements of proliferating mammalian cells. However, genome-scale modeling predicts a catabolic role with one-carbon release as formate. We experimentally prove that in cultured cancer cells and nontransformed fibroblasts, most of the serine-derived one-carbon units are released from cells as formate, and that formate release is dependent on mitochondrial reverse 10-CHO-THF synthetase activity. We also show that in cancer cells, formate release is coupled to mitochondrial complex I activity, whereas in nontransformed fibroblasts, it is partially insensitive to inhibition of complex I activity...
October 2016: Science Advances
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