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Flux balance analysis

Mehak Kaushal, K Venkata Narayana Chary, Saumya Ahlawat, Basavaraj Palabhanvi, Gargi Goswami, Debasish Das
Flux Balance Analysis was performed for Clostridium sporogenes NCIM 2918 grown on sole glucose and glycerol or glucose-glycerol combinations at varied concentrations. During acidogenesis, glucose and glucose-glycerol combinations favored improved growth and butyric acid production. Glycerol fermentation was however marked by reduced growth and predominant ethanol synthesis. Further, with increase of glycerol fraction in glucose-glycerol blend, flux towards ethanol synthesis linearly increased with simultaneous decrease in butanol flux...
November 1, 2017: Bioresource Technology
Anna K Liljedahl, Larry D Hinzman, Douglas L Kane, Walter C Oechel, Craig E Tweedie, Donatella Zona
Difficulties in obtaining accurate precipitation measurements have limited meaningful hydrologic assessment for over a century due to performance challenges of conventional snowfall and rainfall gauges in windy environments. Here, we compare snowfall observations and bias adjusted snowfall to end-of-winter snow accumulation measurements on the ground for 16 years (1999-2014) and assess the implication of precipitation underestimation on the water balance for a low-gradient tundra wetland near Utqiagvik (formerly Barrow), Alaska (2007-2009)...
August 2017: Water Resources Research
Ran Yu, Octavio Perez-Garcia, Huijie Lu, Kartik Chandran
In suboxic or anoxic environments, nitrous oxide (N2O) can be produced by ammonia oxidizing bacteria (AOB) as a potent greenhouse gas. Although N2O producing inventory and pathways have been well-characterized using archetypal AOB, there is little known about their adaptive responses to oxic-anoxic cycling, which is a prevalent condition in soil, sediment, and wastewater treatment bioreactors. In this study, cellular responses of Nitrosomonas europaea 19718 to sustained anoxic-oxic cycling in a chemostat bioreactor were evaluated at transcriptomic, proteomic, and fluxomic levels...
February 15, 2018: Science of the Total Environment
Christopher P Long, Jacqueline E Gonzalez, Robert M Cipolla, Maciek R Antoniewicz
Vibrio natriegens is a fast-growing, non-pathogenic bacterium that is being considered as the next-generation workhorse for the biotechnology industry. However, little is known about the metabolism of this organism which is limiting our ability to apply rational metabolic engineering strategies. To address this critical gap in current knowledge, here we have performed a comprehensive analysis of V. natriegens metabolism. We constructed a detailed model of V. natriegens core metabolism, measured the biomass composition, and performed high-resolution (13)C metabolic flux analysis ((13)C-MFA) to estimate intracellular fluxes using parallel labeling experiments with the optimal tracers [1,2-(13)C]glucose and [1,6-(13)C]glucose...
October 16, 2017: Metabolic Engineering
Lauren T Cordova, Robert M Cipolla, Adti Swarup, Christopher P Long, Maciek R Antoniewicz
Thermophilic organisms are being increasingly investigated and applied in metabolic engineering and biotechnology. The distinct metabolic and physiological characteristics of thermophiles, including broad substrate range and high uptake rates, coupled with recent advances in genetic tool development, present unique opportunities for strain engineering. However, poor understanding of the cellular physiology and metabolism of thermophiles has limited the application of systems biology and metabolic engineering tools to these organisms...
October 14, 2017: Metabolic Engineering
Siu H J Chan, Jingyi Cai, Lin Wang, Margaret N Simons-Senftle, Costas D Maranas
Motivation: In a genome-scale metabolic model, the biomass produced is defined to have a molecular weight (MW) of 1 g mmol-1. This is critical for correctly predicting growth yields, contrasting multiple models and more importantly modeling microbial communities. However, the standard is rarely verified in the current practice and the chemical formulae of biomass components such as proteins, nucleic acids and lipids are often represented by undefined side groups (e.g. X, R). Results: We introduced a systematic procedure for checking the biomass weight and ensuring complete mass balance of a model...
November 15, 2017: Bioinformatics
Åsa Kasimir, Hongxing He, Jessica Coria, Anna Nordén
Drained peatlands are hotspots for greenhouse gas (GHG) emissions, which could be mitigated by rewetting and land use change. We performed an ecological/economic analysis of rewetting drained fertile peatlands in a hemiboreal climate using different land use strategies over 80 years. Vegetation, soil processes, and total GHG emissions were modeled using the CoupModel for four scenarios: 1) business as usual - Norway spruce with average soil water table of -40 cm; 2) willow with groundwater at -20 cm; 3) reed canary grass with groundwater at -10 cm; and 4) a fully rewetted peatland...
October 10, 2017: Global Change Biology
Austin D Comer, Matthew R Long, Jennifer L Reed, Brian F Pfleger
The low cost of natural gas has driven significant interest in using C1 carbon sources (e.g. methane, methanol, CO, syngas) as feedstocks for producing liquid transportation fuels and commodity chemicals. Given the large contribution of sugar and lignocellulosic feedstocks to biorefinery operating costs, natural gas and other C1 sources may provide an economic advantage. To assess the relative costs of these feedstocks, we performed flux balance analysis on genome-scale metabolic models to calculate the maximum theoretical yields of chemical products from methane, methanol, acetate, and glucose...
December 2017: Metabolic Engineering Communications
Meltem Apaydin, Liang Xu, Bo Zeng, Xiaoning Qian
BACKGROUND: Flux Balance Analysis (FBA) based mathematical modeling enables in silico prediction of systems behavior for genome-scale metabolic networks. Computational methods have been derived in the FBA framework to solve bi-level optimization for deriving "optimal" mutant microbial strains with targeted biochemical overproduction. The common inherent assumption of these methods is that the surviving mutants will always cooperate with the engineering objective by overproducing the maximum desired biochemicals...
October 3, 2017: BMC Genomics
Junhua Wang, Cheng Wang, Kejing Song, Jianping Wen
BACKGROUND: Ascomycin is a 23-membered polyketide macrolide with high immunosuppressant and antifungal activity. As the lower production in bio-fermentation, global metabolic analysis is required to further explore its biosynthetic network and determine the key limiting steps for rationally engineering. To achieve this goal, an engineering approach guided by a metabolic network model was implemented to better understand ascomycin biosynthesis and improve its production. RESULTS: The metabolic conservation of Streptomyces species was first investigated by comparing the metabolic enzymes of Streptomyces coelicolor A3(2) with those of 31 Streptomyces strains, the results showed that more than 72% of the examined proteins had high sequence similarity with counterparts in every surveyed strain...
October 3, 2017: Microbial Cell Factories
Zhengwei Xie, Tianyu Zhang, Qi Ouyang
Motivation: One of the long-expected goals of genome-scale metabolic modelling is to evaluate the influence of the perturbed enzymes on flux distribution. Both ordinary differential equation (ODE) models and constraint-based models, like Flux balance analysis (FBA), lack the capacity to perform metabolic control analysis (MCA) for large-scale networks. Results: In this study, we developed a hyper-cube shrink algorithm (HCSA) to incorporate the enzymatic properties into the FBA model by introducing a pseudo reaction V constrained by enzymatic parameters...
September 13, 2017: Bioinformatics
Chiara Damiani, Riccardo Colombo, Daniela Gaglio, Fabrizia Mastroianni, Dario Pescini, Hans Victor Westerhoff, Giancarlo Mauri, Marco Vanoni, Lilia Alberghina
Cancer cells share several metabolic traits, including aerobic production of lactate from glucose (Warburg effect), extensive glutamine utilization and impaired mitochondrial electron flow. It is still unclear how these metabolic rearrangements, which may involve different molecular events in different cells, contribute to a selective advantage for cancer cell proliferation. To ascertain which metabolic pathways are used to convert glucose and glutamine to balanced energy and biomass production, we performed systematic constraint-based simulations of a model of human central metabolism...
September 2017: PLoS Computational Biology
Shaozhen Ding, Xiaoping Liao, Weizhong Tu, Ling Wu, Yu Tian, Qiuping Sun, Junni Chen, Qian-Nan Hu
Developing computational tools for a chassis-centered biosynthetic pathway design is very important for a productive heterologous biosynthesis system by considering enormous foreign biosynthetic reactions. For many cases, a pathway to produce a target molecule consists of both native and heterologous reactions when utilizing a microbial organism as the host organism. Due to tens of thousands of biosynthetic reactions existing in nature, it is not trivial to identify which could be served as heterologous ones to produce the target molecule in a specific organism...
November 17, 2017: ACS Chemical Biology
Christopher P Long, Jacqueline E Gonzalez, Adam M Feist, Bernhard O Palsson, Maciek R Antoniewicz
Adaptive laboratory evolution (ALE) is a widely-used method for improving the fitness of microorganisms in selected environmental conditions. It has been applied previously to Escherichia coli K-12 MG1655 during aerobic exponential growth on glucose minimal media, a frequently used model organism and growth condition, to probe the limits of E. coli growth rate and gain insights into fast growth phenotypes. Previous studies have described up to 1.6-fold increases in growth rate following ALE, and have identified key causal genetic mutations and changes in transcriptional patterns...
September 23, 2017: Metabolic Engineering
Fumio Matsuda, Yoshihiro Toya, Hiroshi Shimizu
Quantitative analysis of metabolism has been used to identify driver reactions occurring during cancer development and bottleneck reactions in the metabolic engineering of microorganisms. In this review, we compare the advantages and disadvantages of various metabolic analysis methods. We emphasize that metabolic flux analysis based on material balance is a critical method for quantitative investigations into cell metabolism. The absolute determination of metabolite concentration appears to be essential for evaluating the thermodynamic state of metabolism...
September 18, 2017: Biotechnology Advances
Si Nga Sou, Ken Lee, Kalpana Nayyar, Karen M Polizzi, Christopher Sellick, Cleo Kontoravdi
Transient gene expression (TGE) is a methodology employed in bioprocessing for the fast provision of recombinant protein material. Mild hypothermia is often introduced to overcome the low yield typically achieved with TGE and improve specific protein productivity. It is therefore of interest to examine the impact of mild hypothermic temperatures on both the yield and quality of transiently-expressed proteins and the relationship to changes in cellular processes and metabolism. In this study, we focus on the ability of a Chinese hamster ovary cell line to galactosylate a recombinant monoclonal antibody (mAb) product...
September 16, 2017: Biotechnology and Bioengineering
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 2017: PLoS Computational Biology
Chiara Damiani, Marzia Di Filippo, Dario Pescini, Davide Maspero, Riccardo Colombo, Giancarlo Mauri
Motivation: Intratumour heterogeneity poses many challenges to the treatment of cancer. Unfortunately, the transcriptional and metabolic information retrieved by currently available computational and experimental techniques portrays the average behaviour of intermixed and heterogeneous cell subpopulations within a given tumour. Emerging single-cell genomic analyses are nonetheless unable to characterize the interactions among cancer subpopulations. In this study, we propose popFBA , an extension to classic Flux Balance Analysis, to explore how metabolic heterogeneity and cooperation phenomena affect the overall growth of cancer cell populations...
July 15, 2017: Bioinformatics
Allen M Shapiro, Claire R Tiedeman, Thomas E Imbrigiotta, Daniel J Goode, Paul A Hsieh, Pierre J Lacombe, Mary F DeFlaun, Scott R Drew, Gary P Curtis
A mass balance is formulated to evaluate the mobilization of chlorinated ethene compounds (CE) from the rock matrix of a fractured mudstone aquifer under pre- and postbioremediation conditions. The analysis relies on a sparse number of monitoring locations and is constrained by a detailed description of the groundwater flow regime. Groundwater flow modeling developed under the site characterization identified groundwater fluxes to formulate the CE mass balance in the rock volume exposed to the injected remediation amendments...
September 5, 2017: Ground Water
E Motamedian, E Taheri, F Bagheri
OBJECTIVES: If screening to find effective drugs is possible, the inhibition of proliferation using existing drugs can be a practical strategy to control the drug resistance of cancer. Development of a system-oriented strategy to find effective drugs was the main aim of this research. MATERIALS AND METHODS: An algorithm (transcriptional regulated flux balance analysis [TRFBA]) integrating a generic human metabolic model with transcriptomic data was used to identify genes affecting the growth of drug-resistant cancer cells...
September 3, 2017: Cell Proliferation
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