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Metabolic Modeling (metabolic + modeling)

Distribution by Scientific Domains

Life Sciences	87%

Selected Abstracts

Dynamic Metabolic Modeling for a MAB Bioprocess

BIOTECHNOLOGY PROGRESS, Issue 1 2007
Jianying Gao
Production of monoclonal antibodies (MAb) for diagnostic or therapeutic applications has become an important task in the pharmaceutical industry. The efficiency of high-density reactor systems can be potentially increased by model-based design and control strategies. Therefore, a reliable kinetic model for cell metabolism is required. A systematic procedure based on metabolic modeling is used to model nutrient uptake and key product formation in a MAb bioprocess during both the growth and post-growth phases. The approach combines the key advantages of stoichiometric and kinetic models into a complete metabolic network while integrating the regulation and control of cellular activity. This modeling procedure can be easily applied to any cell line during both the cell growth and post-growth phases. Quadratic programming (QP) has been identified as a suitable method to solve the underdetermined constrained problem related to model parameter identification. The approach is illustrated for the case of murine hybridoma cells cultivated in stirred spinners. [source]

On the reliability of 13C metabolic modeling with two-compartment neuronal-glial models

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2007
Alexander A. Shestov
Abstract Metabolic modeling of 13C NMR spectroscopy (13C MRS) data using two-compartment neuronal-glial models enabled non-invasive measurements of the glutamate-glutamine cycle rate (VNT) in the brain in vivo. However, the reliability of such two-compartment metabolic modeling has not been examined thoroughly. This study uses Monte-Carlo simulations to investigate the reliability of metabolic modeling of 13C positional enrichment time courses measured in brain amino acids such as glutamate and glutamine during [1- 13C]- or [1,6- 13C2]glucose infusion. Results show that the determination of VNT is not very precise under experimental conditions typical of in vivo NMR studies, whereas the neuronal TCA cycle rate VTCA(N) is determined with a much higher precision. Consistent with these results, simulated 13C positional enrichment curves for glutamate and glutamine are much more sensitive to the value of VTCA(N) than to the value of VNT. We conclude that the determination of the glutamate-glutamine cycle rate VNT using 13C MRS is relatively unreliable when fitting 13C positional enrichment curves obtained during [1- 13C] or [1,6- 13C2]glucose infusion. Further developments are needed to improve the determination of VNT, for example using additional information from 13C- 13C isotopomers and/or using glial specific substrates such as [2- 13C]acetate. © 2007 Wiley-Liss, Inc. [source]

Genome-scale models of bacterial metabolism: reconstruction and applications

FEMS MICROBIOLOGY REVIEWS, Issue 1 2009
Maxime Durot
Abstract Genome-scale metabolic models bridge the gap between genome-derived biochemical information and metabolic phenotypes in a principled manner, providing a solid interpretative framework for experimental data related to metabolic states, and enabling simple in silico experiments with whole-cell metabolism. Models have been reconstructed for almost 20 bacterial species, so far mainly through expert curation efforts integrating information from the literature with genome annotation. A wide variety of computational methods exploiting metabolic models have been developed and applied to bacteria, yielding valuable insights into bacterial metabolism and evolution, and providing a sound basis for computer-assisted design in metabolic engineering. Recent advances in computational systems biology and high-throughput experimental technologies pave the way for the systematic reconstruction of metabolic models from genomes of new species, and a corresponding expansion of the scope of their applications. In this review, we provide an introduction to the key ideas of metabolic modeling, survey the methods, and resources that enable model reconstruction and refinement, and chart applications to the investigation of global properties of metabolic systems, the interpretation of experimental results, and the re-engineering of their biochemical capabilities. [source]

On the reliability of 13C metabolic modeling with two-compartment neuronal-glial models

Microalgae for the production of bulk chemicals and biofuels

BIOFUELS, BIOPRODUCTS AND BIOREFINING, Issue 3 2010
Rene H Wijffels
Abstract The feasibility of microalgae production for biodiesel was discussed. Although algae are not yet produced at large scale for bulk applications, there are opportunities to develop this process in a sustainable way. It remains unlikely, however, that the process will be developed for biodiesel as the only end product from microalgae. In order to develop a more sustainable and economically feasible process, all biomass components (e.g. proteins, lipids, carbohydrates) should be used and therefore biorefining of microalgae is very important for the selective separation and use of the functional biomass components. If biorefining of microalgae is applied, lipids should be fractionated into lipids for biodiesel, lipids as a feedstock for the chemical industry and ,-3 fatty acids, proteins and carbohydrates for food, feed and bulk chemicals, and the oxygen produced should be recovered also. If, in addition, production of algae is done on residual nutrient feedstocks and CO2, and production of microalgae is done on a large scale against low production costs, production of bulk chemicals and fuels from microalgae will become economically feasible. In order to obtain that, a number of bottlenecks need to be removed and a multidisciplinary approach in which systems biology, metabolic modeling, strain development, photobioreactor design and operation, scale-up, biorefining, integrated production chain, and the whole system design (including logistics) should be addressed. Copyright © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd [source]