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genome scale metabolic modeling

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https://www.readbyqxmd.com/read/28546903/comprehensive-reconstruction-and-evaluation-of-pichia-pastoris-genome-scale-metabolic-model-that-accounts-for-1243-orfs
#1
Rui Ye, Mingzhi Huang, Hongzhong Lu, Jiangchao Qian, Weilu Lin, Ju Chu, Yingping Zhuang, Siliang Zhang
BACKGROUND: Pichia pastoris is one of the most important cell factories for production of industrial enzymes and heterogenous proteins. The genome-scale metabolic model of high quality is crucial for comprehensive understanding of the P. pastoris metabolism. METHODS: In this paper, we upgraded P. pastoris genome-scale metabolic model based on the combination of latest genome annotations and literatures. Then the performance of the new model was evaluated using the Cobra Toolbox v2...
2017: Bioresources and Bioprocessing
https://www.readbyqxmd.com/read/28544881/mammalian-systems-biotechnology-reveals-global-cellular-adaptations-in-a-recombinant-cho-cell-line
#2
Faraaz Noor Khan Yusufi, Meiyappan Lakshmanan, Ying Swan Ho, Bernard Liat Wen Loo, Pramila Ariyaratne, Yuansheng Yang, Say Kong Ng, Tessa Rui Min Tan, Hock Chuan Yeo, Hsueh Lee Lim, Sze Wai Ng, Ai Ping Hiu, Chung Ping Chow, Corrine Wan, Shuwen Chen, Gavin Teo, Gao Song, Ju Xin Chin, Xiaoan Ruan, Ken Wing Kin Sung, Wei-Shou Hu, Miranda Gek Sim Yap, Muriel Bardor, Niranjan Nagarajan, Dong-Yup Lee
Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28530276/focus-a-metaheuristic-algorithm-for-computing-knockouts-from-genome-scale-models-for-strain-optimization
#3
Sarma Mutturi
Although handful tools are available for constraint-based flux analysis to generate knockout strains, most of these are either based on bilevel-MIP or its modifications. However, metaheuristic approaches that are known for their flexibility and scalability have been less studied. Moreover, in the existing tools, sectioning of search space to find optimal knocks has not been considered. Herein, a novel computational procedure, termed as FOCuS (Flower-pOllination coupled Clonal Selection algorithm), was developed to find the optimal reaction knockouts from a metabolic network to maximize the production of specific metabolites...
May 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28527885/maintenance-of-atp-homeostasis-triggers-metabolic-shifts-in-gas-fermenting-acetogens
#4
Kaspar Valgepea, Renato de Souza Pinto Lemgruber, Kieran Meaghan, Robin William Palfreyman, Tanus Abdalla, Björn Daniel Heijstra, James Bruce Behrendorff, Ryan Tappel, Michael Köpke, Séan Dennis Simpson, Lars Keld Nielsen, Esteban Marcellin
Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1...
May 24, 2017: Cell Systems
https://www.readbyqxmd.com/read/28520105/large-scale-computational-models-of-liver-metabolism-how-far-from-the-clinics
#5
REVIEW
Tanja Cvitanović, Matthias C Reichert, Miha Moškon, Miha Mraz, Frank Lammert, Damjana Rozman
Understanding the dynamics of human liver metabolism is fundamental for effective diagnosis and treatment of liver diseases in general and the metabolism of drugs in particular. This knowledge can be obtained with systems biology/medicine approaches that account for the complexity of hepatic responses and their systemic consequences in other organs. Computational modelling can reveal hidden principles of the system by classification of individual components, analysing their interactions and simulating the effects that are difficult to investigate experimentally...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28511646/emergence-of-microbial-diversity-due-to-cross-feeding-interactions-in-a-spatial-model-of-gut-microbial-metabolism
#6
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/28509388/proteomic-explorations-of-autism-spectrum-disorder
#7
Nicholas Szoko, Adam J McShane, Marvin R Natowicz
Proteomics, the large-scale study of protein expression in cells and tissues, is a powerful tool to study the biology of clinical conditions and has provided significant insights in many experimental systems. Herein, we review the basics of proteomic methodology and discuss challenges in using proteomic approaches to study autism. Unlike other experimental approaches, such as genomic approaches, there have been few large-scale studies of proteins in tissues from persons with autism. Most of the proteomic studies on autism used blood or other peripheral tissues; few studies used brain tissue...
May 16, 2017: Autism Research: Official Journal of the International Society for Autism Research
https://www.readbyqxmd.com/read/28505184/steadycom-predicting-microbial-abundances-while-ensuring-community-stability
#8
Siu Hung Joshua Chan, Margaret N Simons, Costas D Maranas
Genome-scale metabolic modeling has become widespread for analyzing microbial metabolism. Extending this established paradigm to more complex microbial communities is emerging as a promising way to unravel the interactions and biochemical repertoire of these omnipresent systems. While several modeling techniques have been developed for microbial communities, little emphasis has been placed on the need to impose a time-averaged constant growth rate across all members for a community to ensure co-existence and stability...
May 15, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28469704/development-of-a-core-clostridium-thermocellum-kinetic-metabolic-model-consistent-with-multiple-genetic-perturbations
#9
Satyakam Dash, Ali Khodayari, Jilai Zhou, Evert K Holwerda, Daniel G Olson, Lee R Lynd, Costas D Maranas
BACKGROUND: Clostridium thermocellum is a Gram-positive anaerobe with the ability to hydrolyze and metabolize cellulose into biofuels such as ethanol, making it an attractive candidate for consolidated bioprocessing (CBP). At present, metabolic engineering in C. thermocellum is hindered due to the incomplete description of its metabolic repertoire and regulation within a predictive metabolic model. Genome-scale metabolic (GSM) models augmented with kinetic models of metabolism have been shown to be effective at recapitulating perturbed metabolic phenotypes...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28468832/little-fish-big-data-zebrafish-as-a-model-for-cardiovascular-and-metabolic-disease
#10
REVIEW
Philipp Gut, Sven Reischauer, Didier Y R Stainier, Rima Arnaout
The burden of cardiovascular and metabolic diseases worldwide is staggering. The emergence of systems approaches in biology promises new therapies, faster and cheaper diagnostics, and personalized medicine. However, a profound understanding of pathogenic mechanisms at the cellular and molecular levels remains a fundamental requirement for discovery and therapeutics. Animal models of human disease are cornerstones of drug discovery as they allow identification of novel pharmacological targets by linking gene function with pathogenesis...
July 1, 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28455337/laboratory-evolution-to-alternating-substrate-environments-yields-distinct-phenotypic-and-genetic-adaptive-strategies
#11
Troy E Sandberg, Colton J Lloyd, Bernhard O Palsson, Adam M Feist
Adaptive Laboratory Evolution (ALE) experiments are often designed to maintain a static culturing environment to minimize confounding variables that could influence the adaptive process, but dynamic nutrient conditions occur frequently in both natural and bioprocessing settings. To study the nature of carbon substrate fitness tradeoffs, we evolved batch cultures of E. coli via serial propagation into tubes alternating between glucose and either xylose, glycerol, or acetate. Genome sequencing of evolved cultures revealed several genetic changes preferentially selected for under dynamic conditions, and different adaptation strategies depending on the substrates being switched between - in some environments a persistent "generalist" strain developed while in another, two "specialist" subpopulations arose that alternated dominance...
April 28, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28442386/arginine-deiminase-pathway-provides-atp-and-boosts-growth-of-the-gas-fermenting-acetogen-clostridium-autoethanogenum
#12
Kaspar Valgepea, Kim Q Loi, James B Behrendorff, Renato de S P Lemgruber, Manuel Plan, Mark P Hodson, Michael Köpke, Lars K Nielsen, Esteban Marcellin
Acetogens are attractive organisms for the production of chemicals and fuels from inexpensive and non-food feedstocks such as syngas (CO, CO2 and H2). Expanding their product spectrum beyond native compounds is dictated by energetics, particularly ATP availability. Acetogens have evolved sophisticated strategies to conserve energy from reduction potential differences between major redox couples, however, this coupling is sensitive to small changes in thermodynamic equilibria. To accelerate the development of strains for energy-intensive products from gases, we used a genome-scale metabolic model (GEM) to explore alternative ATP-generating pathways in the gas-fermenting acetogen Clostridium autoethanogenum...
April 23, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28433737/exploring-biochemical-pathways-for-mono-ethylene-glycol-meg-synthesis-from-synthesis-gas
#13
M Ahsanul Islam, Noushin Hadadi, Meric Ataman, Vassily Hatzimanikatis, Gregory Stephanopoulos
Mono-ethylene glycol (MEG) is an important petrochemical with widespread use in numerous consumer products. The current industrial MEG-production process relies on non-renewable fossil fuel-based feedstocks, such as petroleum, natural gas, and naphtha; hence, it is useful to explore alternative routes of MEG-synthesis from gases as they might provide a greener and more sustainable alternative to the current production methods. Technologies of synthetic biology and metabolic engineering of microorganisms can be deployed for the expression of new biochemical pathways for MEG-synthesis from gases, provided that such promising alternative routes are first identified...
April 19, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28433724/whole-genome-de-novo-sequencing-of-wood-rot-fungus-fomitopsis-palustris-atcc62978-with-both-a-cellulolytic-and-ligninolytic-enzyme-system
#14
Chang-Young Hong, Su-Yeon Lee, Sun-Hwa Ryu, Myungkil Kim
Fomitopsis palustris is a model brown rot fungus causing destructive wood decay based on the cellulase system. Endoglucanase secreted by F. palustris hydrolyzes cellulose in both the crystalline and amorphous form. In this study, whole-genome sequencing was conducted to identify genes related to F. palustris cellulose degradation and their functions. We determined the 43-Mb complete draft genome of F. palustris (ATCC 62978), comprising 14,592 predicted gene models. Gene annotation provided crucial information about the location and function of protein-encoding genes...
April 19, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28424673/genome-scale-reconstruction-of-the-metabolic-network-in-oenococcus-oeni-to-assess-wine-malolactic-fermentation
#15
Sebastián N Mendoza, Pablo M Cañón, Ángela Contreras, Magdalena Ribbeck, Eduardo Agosín
Oenococcus oeni is the main responsible agent for malolactic fermentation in wine, an unpredictable and erratic process in winemaking. To address this, we have constructed and exhaustively curated the first genome-scale metabolic model of Oenococcus oeni, comprising 660 reactions, 536 metabolites and 454 genes. In silico experiments revealed that nutritional requirements are predicted with an accuracy of 93%, while 14 amino acids were found to be essential for the growth of this bacterial species. When the model was applied to determine the non-growth associated maintenance, results showed that O...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28419089/erroneous-energy-generating-cycles-in-published-genome-scale-metabolic-networks-identification-and-removal
#16
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/28396843/clostridioides-difficile-630%C3%AE-erm-in-silico-and-in-vivo-quantitative-growth-and-extensive-polysaccharide-secretion
#17
Henning Dannheim, Sabine E Will, Dietmar Schomburg, Meina Neumann-Schaal
Antibiotic-associated infections with Clostridioides difficile are a severe and often lethal risk for hospitalized patients, and can also affect populations without these classical risk factors. For a rational design of therapeutical concepts, a better knowledge of the metabolism of the pathogen is crucial. Metabolic modeling can provide a simulation of quantitative growth and usage of metabolic pathways, leading to a deeper understanding of the organism. Here, we present an elaborate genome-scale metabolic model of C...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28389638/imgmd-a-platform-for-the-integration-and-standardisation-of-in-silico-microbial-genome-scale-metabolic-models
#18
Chao Ye, Nan Xu, Chuan Dong, Yuannong Ye, Xuan Zou, Xiulai Chen, Fengbiao Guo, Liming Liu
Genome-scale metabolic models (GSMMs) constitute a platform that combines genome sequences and detailed biochemical information to quantify microbial physiology at the system level. To improve the unity, integrity, correctness, and format of data in published GSMMs, a consensus IMGMD database was built in the LAMP (Linux + Apache + MySQL + PHP) system by integrating and standardizing 328 GSMMs constructed for 139 microorganisms. The IMGMD database can help microbial researchers download manually curated GSMMs, rapidly reconstruct standard GSMMs, design pathways, and identify metabolic targets for strategies on strain improvement...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385593/a-genome-scale-model-of-geobacillus-thermoglucosidasius-c56-ys93-reveals-its-biotechnological-potential-on-rice-straw-hydrolysate
#19
Ahmad Ahmad, Hassan B Hartman, S Krishnakumar, David A Fell, Mark G Poolman, Shireesh Srivastava
Rice straw is a major crop residue which is burnt in many countries, creating significant air pollution. Thus, alternative routes for disposal of rice straw are needed. Biotechnological treatment of rice straw hydrolysate has potential to convert this agriculture waste into valuable biofuel(s) and platform chemicals. Geobacillus thermoglucosidasius is a thermophile with properties specially suited for use as a biocatalyst in lignocellulosic bioprocesses, such as high optimal temperature and tolerance to high levels of ethanol...
April 4, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28385592/genome-scale-metabolic-modelling-common-cofactors-metabolism-in-microorganisms
#20
Nan Xu, Chao Ye, Xiulai Chen, Jia Liu, Liming Liu
The common cofactors ATP/ADP, NAD(P)(H), and acetyl-CoA/CoA are indispensable participants in biochemical reactions in industrial microbes. To systematically explore the effects of these cofactors on cell growth and metabolic phenotypes, the first genome-scale cofactor metabolic model, icmNX6434, including 6434 genes, 1782 metabolites, and 6877 reactions, was constructed from 14 genome-scale metabolic models of 14 industrial strains. The origin, consumption, and interactions of these common cofactors in microbial cells were elucidated by the icmNX6434 model, and they played important roles in cell growth...
April 4, 2017: Journal of Biotechnology
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