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Subrmanian2015 - Energy metabolism of Leishmania infantum, constrain-based metabolic model

ABSTRACT: The uploaded model is linked to the PLoS ONE article: Subramanian A, Jhawar J, Sarkar RR (2015) Dissecting Leishmania infantum Energy Metabolism - A Systems Perspective. PLoS ONE 10(9): e0137976. https://doi.org/10.1371/journal.pone.0137976. The reconstructed network consists of 142 genes encoding for enzymes performing 237 reactions distributed across five distinct model compartments. We annotated the subcellular locations of different enzymes and their reactions on the basis of strong literature evidence and sequence-based detection of cellular localization signal within a protein sequence. We also predicted an extensive set of lethal reaction knockouts; some of which were validated using published data on Leishmania species. Performing a robustness analysis, the model was rigorously validated and tested for the secretion of overflow metabolites specific to Leishmania under varying extracellular oxygen uptake rate. Stage-specific scenarios of L. infantum energy metabolism were incorporated in the model and key metabolic differences were outlined. Analysis of the model revealed the essentiality of glucose uptake, succinate fermentation, glutamate biosynthesis and an active TCA cycle as driving forces for parasite energy metabolism and its optimal growth. Finally, through our in silico knockout analysis, we could identify possible therapeutic targets that provide experimentally testable hypotheses.

SUBMITTER: Abhishek Subramanian

PROVIDER: MODEL2010130002 | BioModels | 2020-10-13

REPOSITORIES: BioModels

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Project description:Wodke2013 - Genome-scale constraint-based model of M.pneumoniae energy metabolism (iJW145) A new genome-scale metabolic reconstruction of M.pneumoniae is used in combination with external metabolite measurement and protein abundance measurements to quantitatively explore the energy metabolism of this genome-reduce human pathogen. This model is described in the article: Dissecting the energy metabolism in Mycoplasma pneumoniae through genome-scale metabolic modeling. Wodke JA, Puchałka J, Lluch-Senar M, Marcos J, Yus E, Godinho M, Gutiérrez-Gallego R, dos Santos VA, Serrano L, Klipp E, Maier T. Mol Syst Biol. 2013;9:653. Abstract: Mycoplasma pneumoniae, a threatening pathogen with a minimal genome, is a model organism for bacterial systems biology for which substantial experimental information is available. With the goal of understanding the complex interactions underlying its metabolism, we analyzed and characterized the metabolic network of M. pneumoniae in great detail, integrating data from different omics analyses under a range of conditions into a constraint-based model backbone. Iterating model predictions, hypothesis generation, experimental testing, and model refinement, we accurately curated the network and quantitatively explored the energy metabolism. In contrast to other bacteria, M. pneumoniae uses most of its energy for maintenance tasks instead of growth. We show that in highly linear networks the prediction of flux distributions for different growth times allows analysis of time-dependent changes, albeit using a static model. By performing an in silico knock-out study as well as analyzing flux distributions in single and double mutant phenotypes, we demonstrated that the model accurately represents the metabolism of M. pneumoniae. The experimentally validated model provides a solid basis for understanding its metabolic regulatory mechanisms. This model is hosted on BioModels Database and identified by: MODEL1301290000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Subrmanian2015 - Energy metabolism of Leishmania infantum, constrain-based metabolic model

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