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genome scale metabolic modeling

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https://www.readbyqxmd.com/read/29792930/functional-genomics-for-the-oleaginous-yeast-yarrowia-lipolytica
#1
Kurt Patterson, James Yu, Jenny Landberg, Ivan Chang, Farbod Shavarebi, Virginia Bilanchone, Suzanne Sandmeyer
Oleaginous yeasts are valuable systems for biosustainable production of hydrocarbon-based chemicals. Yarrowia lipolytica is one of the best characterized of these yeast with respect to genome annotation and flux analysis of metabolic processes. Nonetheless, progress is hampered by a dearth of genome-wide tools enabling functional genomics. In order to remedy this deficiency, we developed a library of Y. lipolytica insertion mutants via transposon mutagenesis. The Hermes DNA transposon was expressed to achieve saturation mutagenesis of the genome...
May 21, 2018: Metabolic Engineering
https://www.readbyqxmd.com/read/29791443/traceability-reproducibility-and-wiki-exploration-for-%C3%A3-la-carte-reconstructions-of-genome-scale-metabolic-models
#2
Méziane Aite, Marie Chevallier, Clémence Frioux, Camille Trottier, Jeanne Got, María Paz Cortés, Sebastián N Mendoza, Grégory Carrier, Olivier Dameron, Nicolas Guillaudeux, Mauricio Latorre, Nicolás Loira, Gabriel V Markov, Alejandro Maass, Anne Siegel
Genome-scale metabolic models have become the tool of choice for the global analysis of microorganism metabolism, and their reconstruction has attained high standards of quality and reliability. Improvements in this area have been accompanied by the development of some major platforms and databases, and an explosion of individual bioinformatics methods. Consequently, many recent models result from "à la carte" pipelines, combining the use of platforms, individual tools and biological expertise to enhance the quality of the reconstruction...
May 23, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29787798/comprehensive-analysis-of-a-metabolic-model-for-lipid-production-in-rhodosporidium-toruloides
#3
María Teresita Castañeda, Sebastián Nuñez, Fabricio Garelli, Claudio Voget, Hernán De Battista
The yeast Rhodosporidium toruloides has been extensively studied for its application in biolipid production. The knowledge of its metabolism capabilities and the application of constraint-based flux analysis methodology provide useful information for process prediction and optimization. The accuracy of the resulting predictions is highly dependent on metabolic models. A metabolic reconstruction for R. toruloides metabolism has been recently published. On the basis of this model, we developed a curated version that unblocks the central nitrogen metabolism and, in addition, completes charge and mass balances in some reactions neglected in the former model...
May 19, 2018: Journal of Biotechnology
https://www.readbyqxmd.com/read/29783050/disruption-of-ergosterol-and-tryptophan-biosynthesis-as-well-as-cell-wall-integrity-pathway-and-the-intracellular-ph-homeostasis-lead-to-mono-2-ethylhexyl-phthalate-toxicity-in-budding-yeast
#4
Linghuo Jiang, Litong Wang, Tianshu Fang, Vassilios Papadopoulos
Endocrine disrupting chemicals (EDCs) are substances in the environment, food, and consumer products that interfere with hormone homeostasis, metabolism or reproduction in humans and animals. One such EDC, the plasticizer di-(2-ethylhexyl)-phthalate (DEHP), exerts its function through its principal bioactive metabolite, mono-(2-ethylhexyl)-phthalate (MEHP). To fully understand the effects of MEHP on cellular processes and metabolism as well as to assess the impact of genetic alteration on the susceptibility to MEHP-induced toxicity, we screened MEHP-sensitive mutations on a genome-scale in the eukaryotic model organism Saccharomyces cerevisiae...
May 15, 2018: Chemosphere
https://www.readbyqxmd.com/read/29772713/genetic-optimization-algorithm-for-metabolic-engineering-revisited
#5
Tobias B Alter, Lars M Blank, Birgitta E Ebert
To date, several independent methods and algorithms exist for exploiting constraint-based stoichiometric models to find metabolic engineering strategies that optimize microbial production performance. Optimization procedures based on metaheuristics facilitate a straightforward adaption and expansion of engineering objectives, as well as fitness functions, while being particularly suited for solving problems of high complexity. With the increasing interest in multi-scale models and a need for solving advanced engineering problems, we strive to advance genetic algorithms, which stand out due to their intuitive optimization principles and the proven usefulness in this field of research...
May 16, 2018: Metabolites
https://www.readbyqxmd.com/read/29761447/integration-of-plant-metabolomics-data-with-metabolic-networks-progresses-and-challenges
#6
Nadine Töpfer, Samuel M D Seaver, Asaph Aharoni
In the last decade, plant genome-scale modeling has developed rapidly and modeling efforts have advanced from representing metabolic behavior of plant heterotrophic cell suspensions to studying the complex interplay of cell types, tissues, and organs. A crucial driving force for such developments is the availability and integration of "omics" data (e.g., transcriptomics, proteomics, and metabolomics) which enable the reconstruction, extraction, and application of context-specific metabolic networks...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29748819/recent-advances-in-steroidal-saponins-biosynthesis-and-in-vitro-production
#7
REVIEW
Swati Upadhyay, Gajendra Singh Jeena, Shikha, Rakesh Kumar Shukla
Steroidal saponins exhibited numerous pharmacological activities due to the modification of their backbone by different cytochrome P450s (P450) and UDP glycosyltransferases (UGTs). Plant-derived steroidal saponins are not sufficient for utilizing them for commercial purpose so in vitro production of saponin by tissue culture, root culture, embryo culture, etc, is necessary for its large-scale production. Saponin glycosides are the important class of plant secondary metabolites, which consists of either steroidal or terpenoidal backbone...
May 10, 2018: Planta
https://www.readbyqxmd.com/read/29745852/transcriptomic-and-metabolic-flux-analyses-reveal-shift-of-metabolic-patterns-during-rice-grain-development
#8
Fangzhou Shen, Xueting Wu, Luoxi Shi, Hang Zhang, Yangmin Chen, Xiaoquan Qi, Zhuo Wang, Xuan Li
BACKGROUND: Rice (Oryza sativa) is one of the most important grain crops, which serves as food source for nearly half of the world population. The study of rice development process as well as related strategies for production has made significant progress. However, the comprehensive study on development of different rice tissues at both transcriptomic and metabolic flux level across different stages was lacked. RESULTS: In this study, we performed RNA-Seq and characterized the expression profiles of differentiated tissues from Oryza sativa Zhonghua 11, including leaves, sheath, stamen, pistil, lemma and palea of the booting stage, and embryo, endosperm, lemma and palea of the mature grain stage...
April 24, 2018: BMC Systems Biology
https://www.readbyqxmd.com/read/29738521/machine-learning-identifies-signatures-of-host-adaptation-in-the-bacterial-pathogen-salmonella-enterica
#9
Nicole E Wheeler, Paul P Gardner, Lars Barquist
Emerging pathogens are a major threat to public health, however understanding how pathogens adapt to new niches remains a challenge. New methods are urgently required to provide functional insights into pathogens from the massive genomic data sets now being generated from routine pathogen surveillance for epidemiological purposes. Here, we measure the burden of atypical mutations in protein coding genes across independently evolved Salmonella enterica lineages, and use these as input to train a random forest classifier to identify strains associated with extraintestinal disease...
May 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29735428/assessing-flux-distribution-associated-with-metabolic-specialization-of-glandular-trichomes
#10
REVIEW
Jordan J Zager, B Markus Lange
Many aromatic plants accumulate mixtures of secondary (or specialized) metabolites in anatomical structures called glandular trichomes (GTs). Different GT types may also synthesize different mixtures of secreted metabolites, and this contributes to the enormous chemical diversity reported to occur across species. Over the past two decades, significant progress has been made in characterizing the genes and enzymes that are responsible for the unique metabolic capabilities of GTs in different lineages of flowering plants...
May 4, 2018: Trends in Plant Science
https://www.readbyqxmd.com/read/29731977/constraint-based-modeling-of-metabolism-allows-finding-metabolic-cancer-hallmarks-and-identifying-personalized-therapeutic-windows
#11
Sergio Bordel
In order to choose optimal personalized anticancer treatments, transcriptomic data should be analyzed within the frame of biological networks. The best known human biological network (in terms of the interactions between its different components) is metabolism. Cancer cells have been known to have specific metabolic features for a long time and currently there is a growing interest in characterizing new cancer specific metabolic hallmarks. In this article it is presented a method to find personalized therapeutic windows using RNA-seq data and Genome Scale Metabolic Models...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29729378/leveraging-knowledge-engineering-and-machine-learning-for-microbial-bio-manufacturing
#12
REVIEW
Tolutola Oyetunde, Forrest Sheng Bao, Jiung-Wen Chen, Hector Garcia Martin, Yinjie J Tang
Genome scale modeling (GSM) predicts the performance of microbial workhorses and helps identify beneficial gene targets. GSM integrated with intracellular flux dynamics, omics, and thermodynamics have shown remarkable progress in both elucidating complex cellular phenomena and computational strain design (CSD). Nonetheless, these models still show high uncertainty due to a poor understanding of innate pathway regulations, metabolic burdens, and other factors (such as stress tolerance and metabolite channeling)...
May 2, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29717213/metabolic-systems-analysis-of-lps-induced-endothelial-dysfunction-applied-to-sepsis-patient-stratification
#13
Sarah McGarrity, Ósk Anuforo, Haraldur Halldórsson, Andreas Bergmann, Skarphéðinn Halldórsson, Sirus Palsson, Hanne H Henriksen, Pär Ingemar Johansson, Óttar Rolfsson
Endothelial dysfunction contributes to sepsis outcome. Metabolic phenotypes associated with endothelial dysfunction are not well characterised in part due to difficulties in assessing endothelial metabolism in situ. Here, we describe the construction of iEC2812, a genome scale metabolic reconstruction of endothelial cells and its application to describe metabolic changes that occur following endothelial dysfunction. Metabolic gene expression analysis of three endothelial subtypes using iEC2812 suggested their similar metabolism in culture...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29715508/gut-metabolome-meets-microbiome-a-methodological-perspective-to-understand-the-relationship-between-host-and-microbe
#14
REVIEW
Santosh Lamichhane, Partho Sen, Alex M Dickens, Matej Orešič, Hanne Christine Bertram
It is well established that gut microbes and their metabolic products regulate host metabolism. The interactions between the host and its gut microbiota are highly dynamic and complex. In this review we present and discuss the metabolomic strategies to study the gut microbial ecosystem. We highlight the metabolic profiling approaches to study faecal samples aimed at deciphering the metabolic product derived from gut microbiota. We also discuss how metabolomics data can be integrated with metagenomics data derived from gut microbiota and how such approaches may lead to better understanding of the microbial functions...
April 28, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29704665/synthesis-of-multi-omic-data-and-community-metabolic-models-reveals-insights-into-the-role-of-hydrogen-sulfide-in-colon-cancer
#15
Vanessa L Hale, Patricio Jeraldo, Michael Mundy, Janet Yao, Gary Keeney, Nancy Scott, E Heidi Cheek, Jennifer Davidson, Megan Green, Christine Martinez, John Lehman, Chandra Pettry, Erica Reed, Kelly Lyke, Bryan A White, Christian Diener, Osbaldo Resendis-Antonio, Jaime Gransee, Tumpa Dutta, Xuan-Mai Petterson, Lisa Boardman, David Larson, Heidi Nelson, Nicholas Chia
Multi-omic data and genome-scale microbial metabolic models have allowed us to examine microbial communities, community function, and interactions in ways that were not available to us historically. Now, one of our biggest challenges is determining how to integrate data and maximize data potential. Our study demonstrates one way in which to test a hypothesis by combining multi-omic data and community metabolic models. Specifically, we assess hydrogen sulfide production in colorectal cancer based on stool, mucosa, and tissue samples collected on and off the tumor site within the same individuals...
April 25, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29704438/crispr-interference-mediated-metabolic-engineering-of-corynebacterium-glutamicum-for-homo-butyrate-production
#16
Jinkyung Yoon, Han Min Woo
Combinatorial metabolic engineering enabled the development of efficient microbial cell factories for modulating gene expression to produce desired products. Here, we report the combinatorial metabolic engineering of Corynebacterium glutamicum to produce butyrate by introducing a synthetic butyrate pathway including phosphotransferase and butyrate kinase reactions and repressing the essential acn gene encoding aconitase, which has been targeted for down-regulation in a genome-scale model. An All-in-One CRISPR interference system for C...
April 28, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29692801/icn718-an-updated-and-improved-genome-scale-metabolic-network-reconstruction-of-acinetobacter-baumannii-aye
#17
Charles J Norsigian, Erol Kavvas, Yara Seif, Bernhard O Palsson, Jonathan M Monk
Acinetobacter baumannii has become an urgent clinical threat due to the recent emergence of multi-drug resistant strains. There is thus a significant need to discover new therapeutic targets in this organism. One means for doing so is through the use of high-quality genome-scale reconstructions. Well-curated and accurate genome-scale models (GEMs) of A. baumannii would be useful for improving treatment options. We present an updated and improved genome-scale reconstruction of A. baumannii AYE, named iCN718, that improves and standardizes previous A...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29688451/genome-scale-metabolic-modeling-of-responses-to-polymyxins-in-pseudomonas-aeruginosa
#18
Yan Zhu, Tobias Czauderna, Jinxin Zhao, Matthias Klapperstueck, Mohd Hafidz Mahamad Maifiah, Mei-Ling Han, Jing Lu, Björn Sommer, Tony Velkov, Trevor Lithgow, Jiangning Song, Falk Schreiber, Jian Li
Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients, and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was used to analyze bacterial metabolic changes at the systems level...
April 1, 2018: GigaScience
https://www.readbyqxmd.com/read/29683462/polysome-profiling-in-leishmania-human-cells-and-mouse-testis
#19
Zemfira N Karamysheva, Elena B Tikhonova, Petar N Grozdanov, James C Huffman, Kristen R Baca, Alexander Karamyshev, R Brian Denison, Clinton C MacDonald, Kai Zhang, Andrey L Karamyshev
Proper protein expression at the right time and in the right amounts is the basis of normal cell function and survival in a fast-changing environment. For a long time, the gene expression studies were dominated by research on the transcriptional level. However, the steady-state levels of mRNAs do not correlate well with protein production, and the translatability of mRNAs varies greatly depending on the conditions. In some organisms, like the parasite Leishmania, the protein expression is regulated mostly at the translational level...
April 8, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29672509/robustness-encoded-across-essential-and-accessory-replicons-of-the-ecologically-versatile-bacterium-sinorhizobium-meliloti
#20
George C diCenzo, Alex B Benedict, Marco Fondi, Graham C Walker, Turlough M Finan, Alessio Mengoni, Joel S Griffitts
Bacterial genome evolution is characterized by gains, losses, and rearrangements of functional genetic segments. The extent to which large-scale genomic alterations influence genotype-phenotype relationships has not been investigated in a high-throughput manner. In the symbiotic soil bacterium Sinorhizobium meliloti, the genome is composed of a chromosome and two large extrachromosomal replicons (pSymA and pSymB, which together constitute 45% of the genome). Massively parallel transposon insertion sequencing (Tn-seq) was employed to evaluate the contributions of chromosomal genes to growth fitness in both the presence and absence of these extrachromosomal replicons...
April 19, 2018: PLoS Genetics
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