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Reconstruction and applications of consensus yeast metabolic network based on RNA sequencing.

ABSTRACT: One practical application of genome-scale metabolic reconstructions is to interrogate multispecies relationships. Here, we report a consensus metabolic model in four yeast species (Saccharomyces cerevisiae, S. paradoxus, S. mikatae, and S. bayanus) by integrating metabolic network simulations with RNA sequencing (RNA-seq) datasets. We generated high-resolution transcriptome maps of four yeast species through de novo assembly and genome-guided approaches. The transcriptomes were annotated and applied to build the consensus metabolic network, which was verified using independent RNA-seq experiments. The expression profiles reveal that the genes involved in amino acid and lipid metabolism are highly coexpressed. The diverse phenotypic characteristics, such as cellular growth and gene deletions, can be simulated using the metabolic model. We also explored the applications of the consensus model in metabolic engineering using yeast-specific reactions and biofuel production as examples. Similar strategies will benefit communities studying genome-scale metabolic networks of other organisms.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC4821349 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Reconstruction and applications of consensus yeast metabolic network based on RNA sequencing.

Zhao Yuqi Y Wang Yanjie Y Zou Lei L Huang Jingfei J

FEBS open bio 20160227 4

One practical application of genome-scale metabolic reconstructions is to interrogate multispecies relationships. Here, we report a consensus metabolic model in four yeast species (Saccharomyces cerevisiae, S. paradoxus, S. mikatae, and S. bayanus) by integrating metabolic network simulations with RNA sequencing (RNA-seq) datasets. We generated high-resolution transcriptome maps of four yeast species through de novo assembly and genome-guided approaches. The transcriptomes were annotated and app ...[more]

PMID: 27239440

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Project description:BackgroundEfforts to improve the computational reconstruction of the Saccharomyces cerevisiae biochemical reaction network and to refine the stoichiometrically constrained metabolic models that can be derived from such a reconstruction have continued since the first stoichiometrically constrained yeast genome scale metabolic model was published in 2003. Continuing this ongoing process, we have constructed an update to the Yeast Consensus Reconstruction, Yeast 5. The Yeast Consensus Reconstruction is a product of efforts to forge a community-based reconstruction emphasizing standards compliance and biochemical accuracy via evidence-based selection of reactions. It draws upon models published by a variety of independent research groups as well as information obtained from biochemical databases and primary literature.ResultsYeast 5 refines the biochemical reactions included in the reconstruction, particularly reactions involved in sphingolipid metabolism; updates gene-reaction annotations; and emphasizes the distinction between reconstruction and stoichiometrically constrained model. Although it was not a primary goal, this update also improves the accuracy of model prediction of viability and auxotrophy phenotypes and increases the number of epistatic interactions. This update maintains an emphasis on standards compliance, unambiguous metabolite naming, and computer-readable annotations available through a structured document format. Additionally, we have developed MATLAB scripts to evaluate the model's predictive accuracy and to demonstrate basic model applications such as simulating aerobic and anaerobic growth. These scripts, which provide an independent tool for evaluating the performance of various stoichiometrically constrained yeast metabolic models using flux balance analysis, are included as Additional files 1, 2 and 3.ConclusionsYeast 5 expands and refines the computational reconstruction of yeast metabolism and improves the predictive accuracy of a stoichiometrically constrained yeast metabolic model. It differs from previous reconstructions and models by emphasizing the distinction between the yeast metabolic reconstruction and the stoichiometrically constrained model, and makes both available as Additional file 4 and Additional file 5 and at http://yeast.sf.net/ as separate systems biology markup language (SBML) files. Through this separation, we intend to make the modeling process more accessible, explicit, transparent, and reproducible.

Project description:A cornerstone of biotechnology is the use of microorganisms for the efficient production of chemicals and the elimination of harmful waste. Pseudomonas putida is an archetype of such microbes due to its metabolic versatility, stress resistance, amenability to genetic modifications, and vast potential for environmental and industrial applications. To address both the elucidation of the metabolic wiring in P. putida and its uses in biocatalysis, in particular for the production of non-growth-related biochemicals, we developed and present here a genome-scale constraint-based model of the metabolism of P. putida KT2440. Network reconstruction and flux balance analysis (FBA) enabled definition of the structure of the metabolic network, identification of knowledge gaps, and pin-pointing of essential metabolic functions, facilitating thereby the refinement of gene annotations. FBA and flux variability analysis were used to analyze the properties, potential, and limits of the model. These analyses allowed identification, under various conditions, of key features of metabolism such as growth yield, resource distribution, network robustness, and gene essentiality. The model was validated with data from continuous cell cultures, high-throughput phenotyping data, (13)C-measurement of internal flux distributions, and specifically generated knock-out mutants. Auxotrophy was correctly predicted in 75% of the cases. These systematic analyses revealed that the metabolic network structure is the main factor determining the accuracy of predictions, whereas biomass composition has negligible influence. Finally, we drew on the model to devise metabolic engineering strategies to improve production of polyhydroxyalkanoates, a class of biotechnologically useful compounds whose synthesis is not coupled to cell survival. The solidly validated model yields valuable insights into genotype-phenotype relationships and provides a sound framework to explore this versatile bacterium and to capitalize on its vast biotechnological potential.

Dataset Information

Reconstruction and applications of consensus yeast metabolic network based on RNA sequencing.

Publications

Reconstruction and applications of consensus yeast metabolic network based on RNA sequencing.

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