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Yeast9: A Consensus Yeast Metabolic Model Enables Quantitative Analysis of Cellular Metabolism By Incorporating Big Data

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Genome-scale metabolic models (GEMs) can facilitate metabolism-focused multi-omics integrative analysis. Since Yeast8, the yeast-GEM of Saccharomyces cerevisiae , published in 2019, has been continuously updated by the community. This have increased the quality and scope of this model, culminating now in Yeast9. To evaluate its predictive performance, we generated 163 condition-specific GEMs constrained by single-cell transcriptomics from osmotic pressure or normal conditions. Comparative flux analysis showed that yeast adapting to high osmotic pressure benefits from upregulating fluxes through the central carbon metabolism. Furthermore, combining Yeast9 with proteomics revealed metabolic rewiring underlying its preference in nitrogen sources. Lastly, we created strain-specific GEMs (ssGEMs) constrained by transcriptomics for 1229 mutant strains. Well able to predict the strains’ growth rates, fluxomics from those large-scale ssGEMs outperformed transcriptomics in predicting functional categories for all studied genes in machine-learning models. Based on those findings we anticipate that Yeast9 will empower systems biology studies of yeast metabolism.

Authors 14

  1. East China University of Science and Technology · Shanghai Jiao Tong University · State Key Laboratory of Microbial Metabolism · State Key Laboratory of Bioreactor Engineering

    Affiliation as printed

    State Key Laboratory of Bioreactor Engineering, and School of Biotechnology, East China University of Science and Technology (ECUST), Shanghai, 200237, China,

    State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China,

    State Key Laboratory of Bioreactor Engineering, and School of Biotechnology, East China University of Science and Technology (ECUST), Shanghai, 0037, China,

  2. Tsinghua Shenzhen International Graduate School · Tsinghua University

    Affiliation as printed

    Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China,

    Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 180, China,

  3. Nanyang Technological University

    Affiliation as printed

    School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459,

    School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 2 Nanyang Drive, Singapore 37459,

  4. Wageningen University & Research

    Affiliation as printed

    Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Wageningen, The Netherlands,

    UNLOCK, Wageningen University & Research, Wageningen, The Netherlands,

  5. RWTH Aachen University

    Affiliation as printed

    Institute of Applied Microbiology - iAMB, Aachen Biology and Biotechnology - ABBt, RWTH Aachen University, 52074 Aachen, Germany,

  6. RWTH Aachen University

    Affiliation as printed

    Institute of Applied Microbiology - iAMB, Aachen Biology and Biotechnology - ABBt, RWTH Aachen University, 52074 Aachen, Germany,

  7. RWTH Aachen University

    Affiliation as printed

    Institute of Applied Microbiology - iAMB, Aachen Biology and Biotechnology - ABBt, RWTH Aachen University, 52074 Aachen, Germany,

  8. Science for Life Laboratory · National Bioinformatics Infrastructure Sweden · Chalmers University of Technology

    Affiliation as printed

    Department of Life Sciences, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Chalmers University of Technology, Gothenburg SE412 58, Sweden

  9. Novo Nordisk Foundation · Chalmers University of Technology · Technical University of Denmark

    Affiliation as printed

    Department of Life Sciences, Chalmers University of Technology, Gothenburg SE412 96, Sweden,

    The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kgs Lyngby, Denmark,

  10. Center for Mathematical Modeling · University of Chile · Vrije Universiteit Amsterdam

    Affiliation as printed

    Center for Mathematical Modeling, University of Chile, Santiago, Chile

    Systems Biology Lab, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

  11. East China University of Science and Technology · State Key Laboratory of Bioreactor Engineering

    Affiliation as printed

    State Key Laboratory of Bioreactor Engineering, and School of Biotechnology, East China University of Science and Technology (ECUST), Shanghai, 200237, China,

    State Key Laboratory of Bioreactor Engineering, and School of Biotechnology, East China University of Science and Technology (ECUST), Shanghai, 0037, China,

  12. BioInnovation Institute · Chalmers University of Technology

    Affiliation as printed

    BioInnovation Institute, Ole Maaløes Vej 3, DK2200 Copenhagen N, Denmark,

    Department of Life Sciences, Chalmers University of Technology, Gothenburg SE412 96, Sweden,

  13. Hongzhong Lu corresponding

    Shanghai Jiao Tong University · State Key Laboratory of Microbial Metabolism

    Affiliation as printed

    State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China,

  14. Science for Life Laboratory · Novo Nordisk Foundation · Chalmers University of Technology · Technical University of Denmark

    Affiliation as printed

    Department of Life Sciences, SciLifeLab, Chalmers University of Technology, Gothenburg SE412 96, Sweden

    The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, DK-2800 Kgs Lyngby, Denmark,

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References 81