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Characterizing the metabolism of Dehalococcoides with a constraint-based model.

ABSTRACT: Dehalococcoides strains respire a wide variety of chloro-organic compounds and are important for the bioremediation of toxic, persistent, carcinogenic, and ubiquitous ground water pollutants. In order to better understand metabolism and optimize their application, we have developed a pan-genome-scale metabolic network and constraint-based metabolic model of Dehalococcoides. The pan-genome was constructed from publicly available complete genome sequences of Dehalococcoides sp. strain CBDB1, strain 195, strain BAV1, and strain VS. We found that Dehalococcoides pan-genome consisted of 1118 core genes (shared by all), 457 dispensable genes (shared by some), and 486 unique genes (found in only one genome). The model included 549 metabolic genes that encoded 356 proteins catalyzing 497 gene-associated model reactions. Of these 497 reactions, 477 were associated with core metabolic genes, 18 with dispensable genes, and 2 with unique genes. This study, in addition to analyzing the metabolism of an environmentally important phylogenetic group on a pan-genome scale, provides valuable insights into Dehalococcoides metabolic limitations, low growth yields, and energy conservation. The model also provides a framework to anchor and compare disparate experimental data, as well as to give insights on the physiological impact of "incomplete" pathways, such as the TCA-cycle, CO(2) fixation, and cobalamin biosynthesis pathways. The model, referred to as iAI549, highlights the specialized and highly conserved nature of Dehalococcoides metabolism, and suggests that evolution of Dehalococcoides species is driven by the electron acceptor availability.

SUBMITTER: Ahsanul Islam M

PROVIDER: S-EPMC2930330 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Characterizing the metabolism of Dehalococcoides with a constraint-based model.

Ahsanul Islam M M Edwards Elizabeth A EA Mahadevan Radhakrishnan R

PLoS computational biology 20100819 8

Dehalococcoides strains respire a wide variety of chloro-organic compounds and are important for the bioremediation of toxic, persistent, carcinogenic, and ubiquitous ground water pollutants. In order to better understand metabolism and optimize their application, we have developed a pan-genome-scale metabolic network and constraint-based metabolic model of Dehalococcoides. The pan-genome was constructed from publicly available complete genome sequences of Dehalococcoides sp. strain CBDB1, strai ...[more]

PMID: 20811585

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Project description:BACKGROUND:The complexity of metabolic networks can make the origin and impact of changes in central metabolism occurring during diseases difficult to understand. Computer simulations can help unravel this complexity, and progress has advanced in genome-scale metabolic models. However, many models produce unrealistic results when challenged to simulate abnormal metabolism as they include incorrect specification and localisation of reactions and transport steps, incorrect reaction parameters, and confounding of prosthetic groups and free metabolites in reactions. Other common drawbacks are due to their scale, making them difficult to parameterise and simulation results hard to interpret. Therefore, it remains important to develop smaller, manually curated models. RESULTS:We present MitoCore, a manually curated constraint-based computer model of human metabolism that incorporates the complexity of central metabolism and simulates this metabolism successfully under normal and abnormal physiological conditions, including hypoxia and mitochondrial diseases. MitoCore describes 324 metabolic reactions, 83 transport steps between mitochondrion and cytosol, and 74 metabolite inputs and outputs through the plasma membrane, to produce a model of manageable scale for easy interpretation of results. Its key innovations include a more accurate partitioning of metabolism between cytosol and mitochondrial matrix; better modelling of connecting transport steps; differentiation of prosthetic groups and free co-factors in reactions; and a new representation of the respiratory chain and the proton motive force. MitoCore's default parameters simulate normal cardiomyocyte metabolism, and to improve usability and allow comparison with other models and types of analysis, its reactions and metabolites have extensive annotation, and cross-reference identifiers from Virtual Metabolic Human database and KEGG. These innovations-including over 100 reactions absent or modified from Recon 2-are necessary to model central metabolism more accurately. CONCLUSION:We anticipate MitoCore as a research tool for scientists, from experimentalists looking to interpret their data and test hypotheses, to experienced modellers predicting the consequences of disease or using computationally intensive methods that are infeasible with larger models, as well as a teaching tool for those new to modelling and needing a small, manageable model on which to learn and experiment.

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Dataset Information

Characterizing the metabolism of Dehalococcoides with a constraint-based model.

Publications

Characterizing the metabolism of Dehalococcoides with a constraint-based model.

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