Dataset Information

ReCodLiver0.9: Overcoming Challenges in Genome-Scale Metabolic Reconstruction of a Non-model Species.

ABSTRACT: The availability of genome sequences, annotations, and knowledge of the biochemistry underlying metabolic transformations has led to the generation of metabolic network reconstructions for a wide range of organisms in bacteria, archaea, and eukaryotes. When modeled using mathematical representations, a reconstruction can simulate underlying genotype-phenotype relationships. Accordingly, genome-scale metabolic models (GEMs) can be used to predict the response of organisms to genetic and environmental variations. A bottom-up reconstruction procedure typically starts by generating a draft model from existing annotation data on a target organism. For model species, this part of the process can be straightforward, due to the abundant organism-specific biochemical data. However, the process becomes complicated for non-model less-annotated species. In this paper, we present a draft liver reconstruction, ReCodLiver0.9, of Atlantic cod (Gadus morhua), a non-model teleost fish, as a practicable guide for cases with comparably few resources. Although the reconstruction is considered a draft version, we show that it already has utility in elucidating metabolic response mechanisms to environmental toxicants by mapping gene expression data of exposure experiments to the resulting model.

SUBMITTER: Hanna EM

PROVIDER: S-EPMC7726423 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ReCodLiver0.9: Overcoming Challenges in Genome-Scale Metabolic Reconstruction of a Non-model Species.

Hanna Eileen Marie EM Zhang Xiaokang X Eide Marta M Fallahi Shirin S Furmanek Tomasz T Yadetie Fekadu F Zielinski Daniel Craig DC Goksøyr Anders A Jonassen Inge I

Frontiers in molecular biosciences 20201126

The availability of genome sequences, annotations, and knowledge of the biochemistry underlying metabolic transformations has led to the generation of metabolic network reconstructions for a wide range of organisms in bacteria, archaea, and eukaryotes. When modeled using mathematical representations, a reconstruction can simulate underlying genotype-phenotype relationships. Accordingly, genome-scale metabolic models (GEMs) can be used to predict the response of organisms to genetic and environme ...[more]

PMID: 33324679

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Project description:Since the first in silico generation of a genome-scale metabolic (GSM) model for Haemophilus influenzae in 1999, the GSM models have been reconstructed for various organisms including human and mouse. There are two important strategies for generating a GSM model: in the bottom-up approach, individual genomic and biochemical components are integrated to build a GSM model. Alternatively, the orthology-based strategy uses a previously reconstructed model of a reference organism to infer a GSM model of a target organism. Following the update and development of the metabolic network of reference organism, the model of the target organism can also be updated to eliminate defects. Here, we presented iMM1865 model as an orthology-based reconstruction of a GSM model for Mus musculus based on the last flux-consistent version of the human metabolic network, Recon3D. We proposed two versions of the new mouse model, iMM1865 and min-iMM1865, with the same number of gene-associated reactions but different subsets of non-gene-associated reactions. A third extended but flux-inconsistent model (iMM3254) was also created based on the extended version of Recon3D. Compared to the previously published mouse models, both versions of iMM1865 include more comprehensive annotations of metabolites and reactions with no dead-end metabolites and blocked reactions. We evaluated functionality of the models using 431 metabolic objective functions. iMM1865 and min-iMM1865 passed 93% and 87% of the tests, respectively, while iMM1415 and MMR (another available mouse GSM) passed 80% and 84% of the tests, respectively. Three versions of tissue-specific embryo heart models were also reconstructed from each of iMM1865 and min-iMM1865 using mCADRE algorithm with different thresholds on expression-based scores. The ability of corresponding GSM and embryo heart models to predict essential genes was assessed across experimentally derived lethal and viable gene sets. Our analysis revealed that tissue-specific models render much better predictions than GSM models.

Project description:BACKGROUND: Fermentation of xylose, the major component in hemicellulose, is essential for economic conversion of lignocellulosic biomass to fuels and chemicals. The yeast Scheffersomyces stipitis (formerly known as Pichia stipitis) has the highest known native capacity for xylose fermentation and possesses several genes for lignocellulose bioconversion in its genome. Understanding the metabolism of this yeast at a global scale, by reconstructing the genome scale metabolic model, is essential for manipulating its metabolic capabilities and for successful transfer of its capabilities to other industrial microbes. RESULTS: We present a genome-scale metabolic model for Scheffersomyces stipitis, a native xylose utilizing yeast. The model was reconstructed based on genome sequence annotation, detailed experimental investigation and known yeast physiology. Macromolecular composition of Scheffersomyces stipitis biomass was estimated experimentally and its ability to grow on different carbon, nitrogen, sulphur and phosphorus sources was determined by phenotype microarrays. The compartmentalized model, developed based on an iterative procedure, accounted for 814 genes, 1371 reactions, and 971 metabolites. In silico computed growth rates were compared with high-throughput phenotyping data and the model could predict the qualitative outcomes in 74% of substrates investigated. Model simulations were used to identify the biosynthetic requirements for anaerobic growth of Scheffersomyces stipitis on glucose and the results were validated with published literature. The bottlenecks in Scheffersomyces stipitis metabolic network for xylose uptake and nucleotide cofactor recycling were identified by in silico flux variability analysis. The scope of the model in enhancing the mechanistic understanding of microbial metabolism is demonstrated by identifying a mechanism for mitochondrial respiration and oxidative phosphorylation. CONCLUSION: The genome-scale metabolic model developed for Scheffersomyces stipitis successfully predicted substrate utilization and anaerobic growth requirements. Useful insights were drawn on xylose metabolism, cofactor recycling and mechanism of mitochondrial respiration from model simulations. These insights can be applied for efficient xylose utilization and cofactor recycling in other industrial microorganisms. The developed model forms a basis for rational analysis and design of Scheffersomyces stipitis metabolic network for the production of fuels and chemicals from lignocellulosic biomass.

Dataset Information

ReCodLiver0.9: Overcoming Challenges in Genome-Scale Metabolic Reconstruction of a Non-model Species.

Publications

ReCodLiver0.9: Overcoming Challenges in Genome-Scale Metabolic Reconstruction of a Non-model Species.

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