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Flux balance analysis

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https://www.readbyqxmd.com/read/28606738/engineering-high-level-production-of-fatty-alcohols-by-saccharomyces-cerevisiae-from-lignocellulosic-feedstocks
#1
Leo d'Espaux, Amit Ghosh, Weerawat Runguphan, Maren Wehrs, Feng Xu, Oliver Konzock, Ishaan Dev, Melissa Nhan, Jennifer Gin, Amanda Reider Apel, Christopher J Petzold, Seema Singh, Blake A Simmons, Aindrila Mukhopadhyay, Héctor García Martín, Jay D Keasling
Fatty alcohols in the C12-C18 range are used in personal care products, lubricants, and potentially biofuels. These compounds can be produced from the fatty acid pathway by a fatty acid reductase (FAR), yet yields from the preferred industrial host Saccharomyces cerevisiae remain under 2% of the theoretical maximum from glucose. Here we improved titer and yield of fatty alcohols using an approach involving quantitative analysis of protein levels and metabolic flux, engineering enzyme level and localization, pull-push-block engineering of carbon flux, and cofactor balancing...
June 10, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28606124/remodeling-adipose-tissue-through-in-silico-modulation-of-fat-storage-for-the-prevention-of-type-2-diabetes
#2
Thierry Chénard, Frédéric Guénard, Marie-Claude Vohl, André Carpentier, André Tchernof, Rafael J Najmanovich
BACKGROUND: Type 2 diabetes is one of the leading non-infectious diseases worldwide and closely relates to excess adipose tissue accumulation as seen in obesity. Specifically, hypertrophic expansion of adipose tissues is related to increased cardiometabolic risk leading to type 2 diabetes. Studying mechanisms underlying adipocyte hypertrophy could lead to the identification of potential targets for the treatment of these conditions. RESULTS: We present iTC1390adip, a highly curated metabolic network of the human adipocyte presenting various improvements over the previously published iAdipocytes1809...
June 12, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28600876/rerouting-of-carbon-flux-in-a-glycogen-mutant-of-cyanobacteria-assessed-via-isotopically-non-stationary-13-c-metabolic-flux-analysis
#3
John I Hendry, Charulata Prasannan, Fangfang Ma, K Benedikt Möllers, Damini Jaiswal, Madhuri Digmurti, Doug K Allen, Niels-Ulrik Frigaard, Santanu Dasgupta, Pramod P Wangikar
Cyanobacteria, which constitute a quantitatively dominant phylum, have attracted attention in biofuel applications due to favorable physiological characteristics, high photosynthetic efficiency and amenability to genetic manipulations. However, quantitative aspects of cyanobacterial metabolism have received limited attention. In the present study, we have performed isotopically non-stationary (13) C metabolic flux analysis (INST-(13) C-MFA) to analyze rerouting of carbon in a glycogen synthase deficient mutant strain (glgA-I glgA-II) of the model cyanobacterium Synechococcus sp...
June 10, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28573283/the-effect-of-global-transcriptional-regulators-on-the-anaerobic-fermentative-metabolism-of-escherichia-coli
#4
Manika Kargeti, K V Venkatesh
Global transcription factors are known to regulate the anaerobic growth of Escherichia coli on glucose. These transcription factors help the organism to sense oxygen and accordingly regulate the synthesis of mixed acid producing enzymes. Five global transcription factors, namely ArcA, Fnr, IhfA-B, Crp and Fis, are known to play an important role in the growth phenotype of the organism in the transition from anaerobic to aerobic conditions. The effect of deletion of most of these global transcription factors on the growth phenotype has not been characterized under strict anaerobic fermentation conditions...
June 2, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28571567/clostridium-butyricum-maximizes-growth-while-minimizing-enzyme-usage-and-atp-production-metabolic-flux-distribution-of-a-strain-cultured-in-glycerol
#5
Luis Miguel Serrano-Bermúdez, Andrés Fernando González Barrios, Costas D Maranas, Dolly Montoya
BACKGROUND: The increase in glycerol obtained as a byproduct of biodiesel has encouraged the production of new industrial products, such as 1,3-propanediol (PDO), using biotechnological transformation via bacteria like Clostridium butyricum. However, despite the increasing role of Clostridium butyricum as a bio-production platform, its metabolism remains poorly modeled. RESULTS: We reconstructed iCbu641, the first genome-scale metabolic (GSM) model of a PDO producer Clostridium strain, which included 641 genes, 365 enzymes, 891 reactions, and 701 metabolites...
June 1, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28570967/meta-analysis-of-radiocesium-contamination-data-in-japanese-forest-trees-over-the-period-2011-2013
#6
REVIEW
M-A Gonze, P Calmon
The fate and dispersion of radiocesium in forests affected by the Fukushima atmospheric fallouts have been efficiently characterized by Japanese scientists thanks to monitoring surveys of radioactive contents in contaminated soil, water, and vegetation samples at numerous sites. In this paper, we carry out a meta-analysis of the field surveys conducted over the period 2011-2013 in evergreen coniferous and deciduous broadleaf forests of Fukushima or neighboring prefectures. The review focuses on contamination data acquired in tree vegetation - about 1500 spatio-temporal measurements of concentrations, inventories and depuration fluxes - with a particular interest for organs that were directly exposed to the atmospheric fallouts and subjected to depuration mechanisms (foliage, branches and outer bark)...
May 29, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28542252/metabolic-flux-analysis-of-heterotrophic-growth-in-chlamydomonas-reinhardtii
#7
Nanette R Boyle, Neelanjan Sengupta, John A Morgan
Despite the wealth of knowledge available for C. reinhardtii, the central metabolic fluxes of growth on acetate have not yet been determined. In this study, 13C-metabolic flux analysis (13C-MFA) was used to determine and quantify the metabolic pathways of primary metabolism in C. reinhardtii cells grown under heterotrophic conditions with acetate as the sole carbon source. Isotopic labeling patterns of compartment specific biomass derived metabolites were used to calculate the fluxes. It was found that acetate is ligated with coenzyme A in the three subcellular compartments (cytosol, mitochondria and plastid) included in the model...
2017: PloS One
https://www.readbyqxmd.com/read/28542187/elucidation-of-new-condition-dependent-roles-for-fructose-1-6-bisphosphatase-linked-to-cofactor-balances
#8
Du Toit W P Schabort, Stephanus G Kilian, James C du Preez
The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus...
2017: PloS One
https://www.readbyqxmd.com/read/28531184/bacarena-individual-based-metabolic-modeling-of-heterogeneous-microbes-in-complex-communities
#9
Eugen Bauer, Johannes Zimmermann, Federico Baldini, Ines Thiele, Christoph Kaleta
Recent advances focusing on the metabolic interactions within and between cellular populations have emphasized the importance of microbial communities for human health. Constraint-based modeling, with flux balance analysis in particular, has been established as a key approach for studying microbial metabolism, whereas individual-based modeling has been commonly used to study complex dynamics between interacting organisms. In this study, we combine both techniques into the R package BacArena (https://cran.r-project...
May 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28511646/emergence-of-microbial-diversity-due-to-cross-feeding-interactions-in-a-spatial-model-of-gut-microbial-metabolism
#10
Milan J A van Hoek, Roeland M H Merks
BACKGROUND: The human gut contains approximately 10(14) bacteria, belonging to hundreds of different species. Together, these microbial species form a complex food web that can break down nutrient sources that our own digestive enzymes cannot handle, including complex polysaccharides, producing short chain fatty acids and additional metabolites, e.g., vitamin K. Microbial diversity is important for colonic health: Changes in the composition of the microbiota have been associated with inflammatory bowel disease, diabetes, obesity and Crohn's disease, and make the microbiota more vulnerable to infestation by harmful species, e...
May 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28499817/use-of-cellnetanalyzer-in-biotechnology-and-metabolic-engineering
#11
Axel von Kamp, Sven Thiele, Oliver Hädicke, Steffen Klamt
Mathematical models of the cellular metabolism have become an essential tool for the optimization of biotechnological processes. They help to obtain a systemic understanding of the metabolic processes in the used microorganisms and to find suitable genetic modifications maximizing the production performance. In particular, methods of stoichiometric and constraint-based modeling are frequently used in the context of metabolic and bioprocess engineering. Since metabolic networks can be complex and comprise hundreds or even thousands of metabolites and reactions, dedicated software tools are required for an efficient analysis...
May 10, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28453682/distributedfba-jl-high-level-high-performance-flux-balance-analysis-in-julia
#12
Laurent Heirendt, Ines Thiele, Ronan M T Fleming
Motivation: Flux balance analysis and its variants are widely used methods for predicting steady-state reaction rates in biochemical reaction networks. The exploration of high dimensional networks with such methods is currently hampered by software performance limitations. Results: DistributedFBA.jl is a high-level, high-performance, open-source implementation of flux balance analysis in Julia. It is tailored to solve multiple flux balance analyses on a subset or all the reactions of large and huge-scale networks, on any number of threads or nodes...
May 1, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28444480/model-based-biotechnological-potential-analysis-of-kluyveromyces-marxianus-central-metabolism
#13
A Pentjuss, E Stalidzans, J Liepins, A Kokina, J Martynova, P Zikmanis, I Mozga, R Scherbaka, H Hartman, M G Poolman, D A Fell, A Vigants
The non-conventional yeast Kluyveromyces marxianus is an emerging industrial producer for many biotechnological processes. Here, we show the application of a biomass-linked stoichiometric model of central metabolism that is experimentally validated, and mass and charge balanced for assessing the carbon conversion efficiency of wild type and modified K. marxianus. Pairs of substrates (lactose, glucose, inulin, xylose) and products (ethanol, acetate, lactate, glycerol, ethyl acetate, succinate, glutamate, phenylethanol and phenylalanine) are examined by various modelling and optimisation methods...
April 25, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28444347/fluxomics-links-cellular-functional-analyses-to-whole-plant-phenotyping
#14
Christophe Salon, Jean-Christophe Avice, Sophie Colombié, Martine Dieuaide-Noubhani, Karine Gallardo, Christian Jeudy, Alain Ourry, Marion Prudent, Anne-Sophie Voisin, Dominique Rolin
Fluxes through metabolic pathways reflect the integration of genetic and metabolic regulations. While it is attractive to measure all the mRNAs (transcriptome), all the proteins (proteome), and a large number of the metabolites (metabolome) in a given cellular system, linking and integrating this information remains difficult. Measurement of metabolome-wide fluxes (termed the fluxome) provides an integrated functional output of the cell machinery and a better tool to link functional analyses to plant phenotyping...
April 1, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28432256/global-sensitivity-analysis-of-onguard-models-identifies-key-hubs-for-transport-interaction-in-stomatal-dynamics
#15
Silvere Vialet-Chabrand, Adrian Hills, Yizhou Wang, Howard Griffiths, Virgilio L Lew, Tracy Lawson, Michael R Blatt, Simon Rogers
The physical requirement for charge to balance across biological membranes means that the transmembrane transport of each ionic species is interrelated, and manipulating solute flux through any one transporter will affect other transporters at the same membrane, often with unforeseen consequences. The OnGuard systems modeling platform has helped to resolve the mechanics of stomatal movements, uncovering previously unexpected behaviors of stomata. To date, however, the manual approach to exploring model parameter space has captured little formal information about the emergent connections between parameters that define the most interesting properties of the system as a whole...
June 2017: Plant Physiology
https://www.readbyqxmd.com/read/28429787/heat-temperature-and-clausius-inequality-in-a-model-for-active-brownian-particles
#16
Umberto Marini Bettolo Marconi, Andrea Puglisi, Claudio Maggi
Methods of stochastic thermodynamics and hydrodynamics are applied to a recently introduced model of active particles. The model consists of an overdamped particle subject to Gaussian coloured noise. Inspired by stochastic thermodynamics, we derive from the system's Fokker-Planck equation the average exchanges of heat and work with the active bath and the associated entropy production. We show that a Clausius inequality holds, with the local (non-uniform) temperature of the active bath replacing the uniform temperature usually encountered in equilibrium systems...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28420402/sser-species-specific-essential-reactions-database
#17
Abraham A Labena, Yuan-Nong Ye, Chuan Dong, Fa-Z Zhang, Feng-Biao Guo
BACKGROUND: Essential reactions are vital components of cellular networks. They are the foundations of synthetic biology and are potential candidate targets for antimetabolic drug design. Especially if a single reaction is catalyzed by multiple enzymes, then inhibiting the reaction would be a better option than targeting the enzymes or the corresponding enzyme-encoding gene. The existing databases such as BRENDA, BiGG, KEGG, Bio-models, Biosilico, and many others offer useful and comprehensive information on biochemical reactions...
April 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28419089/erroneous-energy-generating-cycles-in-published-genome-scale-metabolic-networks-identification-and-removal
#18
Claus Jonathan Fritzemeier, Daniel Hartleb, Balázs Szappanos, Balázs Papp, Martin J Lercher
Energy metabolism is central to cellular biology. Thus, genome-scale models of heterotrophic unicellular species must account appropriately for the utilization of external nutrients to synthesize energy metabolites such as ATP. However, metabolic models designed for flux-balance analysis (FBA) may contain thermodynamically impossible energy-generating cycles: without nutrient consumption, these models are still capable of charging energy metabolites (such as ADP→ATP or NADP+→NADPH). Here, we show that energy-generating cycles occur in over 85% of metabolic models without extensive manual curation, such as those contained in the ModelSEED and MetaNetX databases; in contrast, such cycles are rare in the manually curated models of the BiGG database...
April 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28413845/carbon-uptake-by-mature-amazon-forests-has-mitigated-amazon-nations-carbon-emissions
#19
Oliver L Phillips, Roel J W Brienen
BACKGROUND: Several independent lines of evidence suggest that Amazon forests have provided a significant carbon sink service, and also that the Amazon carbon sink in intact, mature forests may now be threatened as a result of different processes. There has however been no work done to quantify non-land-use-change forest carbon fluxes on a national basis within Amazonia, or to place these national fluxes and their possible changes in the context of the major anthropogenic carbon fluxes in the region...
December 2017: Carbon Balance and Management
https://www.readbyqxmd.com/read/28412970/membrane-potential-independent-transport-of-nh3-in-the-absence-of-ammonium-permeases-in-saccharomyces-cerevisiae
#20
Hugo F Cueto-Rojas, Nicholas Milne, Ward van Helmond, Mervin M Pieterse, Antonius J A van Maris, Jean-Marc Daran, S Aljoscha Wahl
BACKGROUND: Microbial production of nitrogen containing compounds requires a high uptake flux and assimilation of the N-source (commonly ammonium), which is generally coupled with ATP consumption and negatively influences the product yield. In the industrial workhorse Saccharomyces cerevisiae, ammonium (NH4(+)) uptake is facilitated by ammonium permeases (Mep1, Mep2 and Mep3), which transport the NH4(+) ion, resulting in ATP expenditure to maintain the intracellular charge balance and pH by proton export using the plasma membrane-bound H(+)-ATPase...
April 17, 2017: BMC Systems Biology
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