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genome scale metabolic modeling

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https://www.readbyqxmd.com/read/28911330/extensive-transcriptomic-and-epigenomic-remodelling-occurs-during-arabidopsis-thaliana-germination
#1
Reena Narsai, Quentin Gouil, David Secco, Akanksha Srivastava, Yuliya V Karpievitch, Lim Chee Liew, Ryan Lister, Mathew G Lewsey, James Whelan
BACKGROUND: Seed germination involves progression from complete metabolic dormancy to a highly active, growing seedling. Many factors regulate germination and these interact extensively, forming a complex network of inputs that control the seed-to-seedling transition. Our understanding of the direct regulation of gene expression and the dynamic changes in the epigenome and small RNAs during germination is limited. The interactions between genome, transcriptome and epigenome must be revealed in order to identify the regulatory mechanisms that control seed germination...
September 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28903046/genome-scale-architecture-of-small-molecule-regulatory-networks-and-the-fundamental-trade-off-between-regulation-and-enzymatic-activity
#2
Ed Reznik, Dimitris Christodoulou, Joshua E Goldford, Emma Briars, Uwe Sauer, Daniel Segrè, Elad Noor
Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets...
September 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/28900755/quantitative-physiology-and-elemental-composition-of-kluyveromyces-lactis-cbs-2359-during-growth-on-glucose-at-different-specific-growth-rates
#3
Oscar Dias, Thiago O Basso, Isabel Rocha, Eugénio C Ferreira, Andreas K Gombert
The yeast Kluyveromyces lactis has received attention both from academia and industry due to some important features, such as its capacity to grow in lactose-based media, its safe status, its suitability for large-scale cultivation and for heterologous protein synthesis. It has also been considered as a model organism for genomics and metabolic regulation. Despite this, very few studies were carried out hitherto under strictly controlled conditions, such as those found in a chemostat. Here we report a set of quantitative physiological data generated during chemostat cultivations with the K...
September 12, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28899034/genome-scale-modeling-of-yeast-chronology-applications-and-critical-perspectives
#4
Helder Lopes, Isabel Rocha
Over the last 15 years, several genome-scale metabolic models (GSMMs) were developed for different yeast species, aiding both the elucidation of new biological processes and the shift toward a bio-based economy, through the design of in silico inspired cell factories. Here, an historical perspective of the GSMMs built over time for several yeast species is presented and the main inheritance patterns among the metabolic reconstructions are highlighted. We additionally provide a critical perspective on the overall genome-scale modeling procedure, underlining incomplete model validation and evaluation approaches and the quest for the integration of regulatory and kinetic information into yeast GSMMs...
August 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28886026/population-fba-predicts-metabolic-phenotypes-in-yeast
#5
Piyush Labhsetwar, Marcelo C R Melo, John A Cole, Zaida Luthey-Schulten
Using protein counts sampled from single cell proteomics distributions to constrain fluxes through a genome-scale model of metabolism, Population flux balance analysis (Population FBA) successfully described metabolic heterogeneity in a population of independent Escherichia coli cells growing in a defined medium. We extend the methodology to account for correlations in protein expression arising from the co-regulation of genes and apply it to study the growth of independent Saccharomyces cerevisiae cells in two different growth media...
September 8, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28884171/model-guided-identification-of-novel-gene-amplification-targets-for-improving-succinate-production-in-escherichia-coli-nzn111
#6
Xingxing Jian, Ningchuan Li, Qian Chen, Qiang Hua
Reconstruction and application of genome-scale metabolic models (GEMs) have facilitated metabolic engineering by providing a platform on which systematic computational analysis of metabolic networks can be performed. In this study, a GEM of Escherichia coli NZN111 was employed by the analysis of production and growth coupling (APGC) algorithm to identify genetic strategies for the overproduction of succinate. Through in silico simulation and reaction expression analysis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), triosephosphate isomerase (TPI), and phosphoenolpyruvate carboxylase (PPC), encoded by gapA, pgk, tpiA, and ppc, respectively, were selected for experimental overexpression...
September 8, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28878200/a-protocol-for-generating-and-exchanging-genome-scale-metabolic-resource-allocation-models
#7
Alexandra-M Reimers, Henning Lindhorst, Steffen Waldherr
In this article, we present a protocol for generating a complete (genome-scale) metabolic resource allocation model, as well as a proposal for how to represent such models in the systems biology markup language (SBML). Such models are used to investigate enzyme levels and achievable growth rates in large-scale metabolic networks. Although the idea of metabolic resource allocation studies has been present in the field of systems biology for some years, no guidelines for generating such a model have been published up to now...
September 6, 2017: Metabolites
https://www.readbyqxmd.com/read/28860532/revealing-the-mystery-of-metabolic-adaptations-using-a-genome-scale-model-of-leishmania-infantum
#8
Abhishek Subramanian, Ram Rup Sarkar
Human macrophage phagolysosome and sandfly midgut provide antagonistic ecological niches for Leishmania parasites to survive and proliferate. Parasites optimize their metabolism to utilize the available inadequate resources by adapting to those environments. Lately, a number of metabolomics studies have revived the interest to understand metabolic strategies utilized by the Leishmania parasite for optimal survival within its hosts. For the first time, we propose a reconstructed genome-scale metabolic model for Leishmania infantum JPCM5, the analyses of which not only captures observations reported by metabolomics studies in other Leishmania species but also divulges novel features of the L...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28845460/integration-of-metabolomics-and-transcriptomics-reveals-a-complex-diet-of-mycobacterium-tuberculosis-during-early-macrophage-infection
#9
Michael Zimmermann, Maria Kogadeeva, Martin Gengenbacher, Gayle McEwen, Hans-Joachim Mollenkopf, Nicola Zamboni, Stefan Hugo Ernst Kaufmann, Uwe Sauer
Nutrient acquisition from the host environment is crucial for the survival of intracellular pathogens, but conceptual and technical challenges limit our knowledge of pathogen diets. To overcome some of these technical roadblocks, we exploited an experimentally accessible model for early infection of human macrophages by Mycobacterium tuberculosis, the etiological agent of tuberculosis, to study host-pathogen interactions with a multi-omics approach. We collected metabolomics and complete transcriptome RNA sequencing (dual RNA-seq) data of the infected macrophages, integrated them in a genome-wide reaction pair network, and identified metabolic subnetworks in host cells and M...
July 2017: MSystems
https://www.readbyqxmd.com/read/28842544/probing-the-genome-scale-metabolic-landscape-of-bordetella-pertussis-the-causative-agent-of-whooping-cough
#10
Filipe Branco Dos Santos, Brett G Olivier, Joost Boele, Vincent Smessaert, Philippe De Rop, Petra Krumpochova, Gunnar W Klau, Martin Giera, Philippe Dehottay, Bas Teusink, Philippe Goffin
Whooping cough is a highly-contagious respiratory disease caused by Bordetella pertussis. Despite vaccination, its incidence has been rising alarmingly, and yet, the physiology of B. pertussis remains poorly understood. We combined genome-scale metabolic reconstruction, a novel optimization algorithm and experimental data to probe the full metabolic potential of this pathogen, using strain Tohama I as a reference. Experimental validation showed that B. pertussis secretes a significant proportion of nitrogen as arginine and purine nucleosides, which may contribute to modulation of the host response...
August 25, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28838953/bioenergetics-of-monoterpenoid-essential-oil-biosynthesis-in-non-photosynthetic-glandular-trichomes
#11
Sean R Johnson, Iris Lange, Narayanan Srividya, Bernd Markus Lange
The commercially important essential oils of peppermint (Mentha x piperita L.) and its relatives in the mint family (Lamiaceae) are accumulated in specialized anatomical structures called glandular trichomes (GTs). A genome-scale stoichiometric model of secretory phase metabolism in peppermint GTs was constructed based on current biochemical and physiological knowledge. Fluxes through the network were predicted based on metabolomic and transcriptomic data. Using simulated reaction deletions, this model predicted that two processes, the regeneration of ATP and ferredoxin (in its reduced form), exert substantial control over flux toward monoterpenes...
August 24, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28836369/wide-scale-comparative-analysis-of-longevity-genes-and-interventions
#12
Hagai Yanai, Arie Budovsky, Thomer Barzilay, Robi Tacutu, Vadim E Fraifeld
Hundreds of genes, when manipulated, affect the lifespan of model organisms (yeast, worm, fruit fly, and mouse) and thus can be defined as longevity-associated genes (LAGs). A major challenge is to determine whether these LAGs are model-specific or may play a universal role as longevity regulators across diverse taxa. A wide-scale comparative analysis of the 1805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially overrepresented, from bacteria to mammals, compared to the entire genomes or interactomes, and this was especially noted for essential LAGs; (ii) the effects on lifespan, when manipulating orthologous LAGs in different model organisms, were mostly concordant, despite a high evolutionary distance between them; (iii) LAGs that have orthologs across a high number of phyla were enriched in translational processes, energy metabolism, and DNA repair genes; (iv) LAGs that have no orthologs out of the taxa in which they were discovered were enriched in autophagy (Ascomycota/Fungi), G proteins (Nematodes), and neuroactive ligand-receptor interactions (Chordata)...
August 24, 2017: Aging Cell
https://www.readbyqxmd.com/read/28822134/genome-scale-modeling-of-photorespiratory-pathway-manipulation
#13
Anika Küken, Zoran Nikoloski
Quantifying the redistribution of metabolic reaction fluxes under experimental scenarios that affect the photorespiratory pathway can provide insights about the coupling of this pathway with other parts of metabolism. However, differential flux profiling on a genome-scale level remains the biggest challenge in modern systems biology. Here we present a protocol for applying a constraint-based approach, termed iReMet-Flux, that integrates data about relative metabolite levels in a stoichiometric metabolic model to predict differential fluxes at a genome-scale level under mild modeling assumptions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28818916/a-pathology-atlas-of-the-human-cancer-transcriptome
#14
Mathias Uhlen, Cheng Zhang, Sunjae Lee, Evelina Sjöstedt, Linn Fagerberg, Gholamreza Bidkhori, Rui Benfeitas, Muhammad Arif, Zhengtao Liu, Fredrik Edfors, Kemal Sanli, Kalle von Feilitzen, Per Oksvold, Emma Lundberg, Sophia Hober, Peter Nilsson, Johanna Mattsson, Jochen M Schwenk, Hans Brunnström, Bengt Glimelius, Tobias Sjöblom, Per-Henrik Edqvist, Dijana Djureinovic, Patrick Micke, Cecilia Lindskog, Adil Mardinoglu, Fredrik Ponten
Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation...
August 18, 2017: Science
https://www.readbyqxmd.com/read/28814793/resolving-the-central-metabolism-of-arabidopsis-guard-cells
#15
Semidán Robaina-Estévez, Danilo M Daloso, Youjun Zhang, Alisdair R Fernie, Zoran Nikoloski
Photosynthesis and water use efficiency, key factors affecting plant growth, are directly controlled by microscopic and adjustable pores in the leaf-the stomata. The size of the pores is modulated by the guard cells, which rely on molecular mechanisms to sense and respond to environmental changes. It has been shown that the physiology of mesophyll and guard cells differs substantially. However, the implications of these differences to metabolism at a genome-scale level remain unclear. Here, we used constraint-based modeling to predict the differences in metabolic fluxes between the mesophyll and guard cells of Arabidopsis thaliana by exploring the space of fluxes that are most concordant to cell-type-specific transcript profiles...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806958/responses-of-synechocystis-sp-pcc-6803-to-heterologous-biosynthetic-pathways
#16
Konstantinos Vavitsas, Emil Østergaard Rue, Lára Kristín Stefánsdóttir, Thiyagarajan Gnanasekaran, Andreas Blennow, Christoph Crocoll, Steinn Gudmundsson, Poul Erik Jensen
BACKGROUND: There are an increasing number of studies regarding genetic manipulation of cyanobacteria to produce commercially interesting compounds. The majority of these works study the expression and optimization of a selected heterologous pathway, largely ignoring the wholeness and complexity of cellular metabolism. Regulation and response mechanisms are largely unknown, and even the metabolic pathways themselves are not fully elucidated. This poses a clear limitation in exploiting the rich biosynthetic potential of cyanobacteria...
August 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28806583/plant-genome-scale-reconstruction-from-single-cell-to-multi-tissue-modelling-and-omics-analyses
#17
REVIEW
Cristiana Gomes de Oliveira Dal'Molin, Lars Keld Nielsen
In this review, we present the latest developments in plant systems biology with particular emphasis on plant genome-scale reconstructions and multi-omics analyses. Understanding multicellular metabolism is far from trivial and 'omics' data are difficult to interpret in the absence of a systems framework. 'Omics' data appropriately integrated with genome-scale reconstructions and modelling facilitates our understanding of how individual components interact and influence overall cell, tissue or organisms function...
August 11, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28805729/systems-biology-approach-to-bioremediation-of-nitroaromatics-constraint-based-analysis-of-2-4-6-trinitrotoluene-biotransformation-by-escherichia-coli
#18
Maryam Iman, Tabassom Sobati, Yunes Panahi, Meysam Mobasheri
Microbial remediation of nitroaromatic compounds (NACs) is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli) has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT). Efforts to develop E. coli as an efficient TNT degrading biocatalyst will benefit from holistic flux-level description of interactions between multiple TNT transforming pathways operating in the strain. To gain such an insight, we extended the genome-scale constraint-based model of E...
August 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28801647/reconstruction-of-a-genome-scale-metabolic-network-of-komagataeibacter-nataicola-rzs01-for-cellulose-production
#19
Heng Zhang, Chao Ye, Nan Xu, Chuntao Chen, Xiao Chen, Fanshu Yuan, Yunhua Xu, Jiazhi Yang, Dongping Sun
Bacterial cellulose (BC) is widely used in industries owing to its high purity and strength. Although Komagataeibacter nataicola is a representative species for BC production, its intracellular metabolism leading to BC secretion is unclear. In the present study, a genome-scale metabolic network of cellulose-producing K. nataicola strain RZS01 was reconstructed to understand its metabolic behavior. This model iHZ771 comprised 771 genes, 2035 metabolites, and 2014 reactions. Constraint-based analysis was used to characterize and evaluate the critical intracellular pathways...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797224/the-adaptive-landscape-of-wildtype-and-glycosylation-deficient-populations-of-the-industrial-yeast-pichia-pastoris
#20
Josef W Moser, Iain B H Wilson, Martin Dragosits
BACKGROUND: The effects of long-term environmental adaptation and the implications of major cellular malfunctions are still poorly understood for non-model but biotechnologically relevant species. In this study we performed a large-scale laboratory evolution experiment with 48 populations of the yeast Pichia pastoris in order to establish a general adaptive landscape upon long-term selection in several glucose-based growth environments. As a model for a cellular malfunction the implications of OCH1 mannosyltransferase knockout-mediated glycosylation-deficiency were analyzed...
August 10, 2017: BMC Genomics
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