Emergence of Orchestrated and Dynamic Metabolism of Saccharomyces cerevisiae

Nguyen, Viviana; Li, Yifei; Lu, Ting

doi:10.1021/acssynbio.3c00542

Emergence of Orchestrated and Dynamic Metabolism of Saccharomyces cerevisiae

Journal Article · Wed Apr 24 00:00:00 EDT 2024 · ACS Synthetic Biology

DOI:https://doi.org/10.1021/acssynbio.3c00542· OSTI ID:2377403

Nguyen, Viviana ^[1]; Li, Yifei ^[2]; ^[2]

University of Illinois Urbana-Champaign, IL (United States); University of Illinois Urbana-Champaign
University of Illinois Urbana-Champaign, IL (United States)

Microbial metabolism is a fundamental cellular process that involves many biochemical events and is distinguished by its emergent properties. While the molecular details of individual reactions have been increasingly elucidated, it is not well understood how these reactions are quantitatively orchestrated to produce collective cellular behaviors. Here we developed a coarse-grained, systems, and dynamic mathematical framework, which integrates metabolic reactions with signal transduction and gene regulation to dissect the emergent metabolic traits of Saccharomyces cerevisiae. Our framework mechanistically captures a set of characteristic cellular behaviors, including the Crabtree effect, diauxic shift, diauxic lag time, and differential growth under nutrient-altered environments. It also allows modular expansion for zooming in on specific pathways for detailed metabolic profiles. Furthermore, this study provides a systems mathematical framework for yeast metabolic behaviors, providing insights into yeast physiology and metabolic engineering.

View Accepted Manuscript (DOE)

Research Organization:: Center for Advanced Bioenergy and Bioproducts Innovation (CABBI), Urbana, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: SC0018420

OSTI ID:: 2377403

Journal Information:: ACS Synthetic Biology, Journal Name: ACS Synthetic Biology Journal Issue: 5 Vol. 13; ISSN 2161-5063

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (74)

Changes in yeast amino acid pool with respiratory versus fermentative metabolism Martíez‐force, Enrique; Benítez, Tahía Biotechnology and Bioengineering, Vol. 40, Issue 6 https://doi.org/10.1002/bit.260400602	journal	September 1992
Comprehensive understanding of Saccharomyces cerevisiae phenotypes with whole‐cell model WM_S288C Ye, Chao; Xu, Nan; Gao, Cong Biotechnology and Bioengineering, Vol. 117, Issue 5 https://doi.org/10.1002/bit.27298	journal	February 2020
Simultaneous utilization of ammonia, free amino acids and peptides during fermentative growth ofSaccharomyces cerevisiae Kevvai, Kaspar; Kütt, Mary-Liis; Nisamedtinov, Ildar Journal of the Institute of Brewing, Vol. 122, Issue 1 https://doi.org/10.1002/jib.298	journal	January 2016
The common message of constraint-based optimization approaches: overflow metabolism is caused by two growth-limiting constraints de Groot, Daan H.; Lischke, Julia; Muolo, Riccardo Cellular and Molecular Life Sciences, Vol. 77, Issue 3 https://doi.org/10.1007/s00018-019-03380-2	journal	November 2019
On the duration of the microbial lag phase Vermeersch, Lieselotte; Perez-Samper, Gemma; Cerulus, Bram Current Genetics, Vol. 65, Issue 3 https://doi.org/10.1007/s00294-019-00938-2	journal	January 2019
Yeast on drugs: Saccharomyces cerevisiae as a tool for anticancer drug research Menacho-Márquez, M.; Murguía, J. R. Clinical and Translational Oncology, Vol. 9, Issue 4 https://doi.org/10.1007/s12094-007-0043-2	journal	April 2007
A biochemically structured model for Saccharomyces cerevisiae Lei, Frede; Rotbøll, Morten; Jørgensen, Sten Bay Journal of Biotechnology, Vol. 88, Issue 3 https://doi.org/10.1016/S0168-1656(01)00269-3	journal	July 2001
Cell design in bacteria as a convex optimization problem Goelzer, Anne; Fromion, Vincent; Scorletti, Gérard Automatica, Vol. 47, Issue 6 https://doi.org/10.1016/j.automatica.2011.02.038	journal	June 2011
Post-translational modifications on yeast carbon metabolism: Regulatory mechanisms beyond transcriptional control Tripodi, Farida; Nicastro, Raffaele; Reghellin, Veronica Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1850, Issue 4 https://doi.org/10.1016/j.bbagen.2014.12.010	journal	April 2015
A new model for the aerobic metabolism of yeast allows the detailed analysis of the metabolic regulation during glucose pulse Kesten, Duygu; Kummer, Ursula; Sahle, Sven Biophysical Chemistry, Vol. 206 https://doi.org/10.1016/j.bpc.2015.06.010	journal	November 2015
Nonlinear programming reformulation of dynamic flux balance analysis models de Oliveira, Rafael D.; Le Roux, Galo A. C.; Mahadevan, Radhakrishnan Computers & Chemical Engineering, Vol. 170 https://doi.org/10.1016/j.compchemeng.2022.108101	journal	February 2023
Metabolic engineering of yeast for production of fuels and chemicals Nielsen, Jens; Larsson, Christer; van Maris, Antonius Current Opinion in Biotechnology, Vol. 24, Issue 3 https://doi.org/10.1016/j.copbio.2013.03.023	journal	June 2013
Yeast models of Parkinson’s disease-associated molecular pathologies Tenreiro, Sandra; Franssens, Vanessa; Winderickx, Joris Current Opinion in Genetics & Development, Vol. 44 https://doi.org/10.1016/j.gde.2017.01.013	journal	June 2017
Effects of minimal media vs. complex media on the metabolite profiles of Escherichia coli and Saccharomyces cerevisiae Kim, Jungyeon; Kim, Kyoung Heon Process Biochemistry, Vol. 57 https://doi.org/10.1016/j.procbio.2017.04.003	journal	June 2017
Controlling circuitry underlies the growth optimization of Saccharomyces cerevisiae Nguyen, Viviana; Xue, Pu; Li, Yifei Metabolic Engineering, Vol. 80 https://doi.org/10.1016/j.ymben.2023.09.013	journal	November 2023
Glucose-Induced Stimulation of the Ras-cAMP Pathway in Yeast Leads to Multiple Phosphorylations and Activation of 6-Phosphofructo-2-kinase Dihazi, Hassan; Kessler, Renate; Eschrich, Klaus Biochemistry, Vol. 42, Issue 20 https://doi.org/10.1021/bi034167r	journal	May 2003
Effects of varying media, temperature, and growth rates on the intracellular concentrations of yeast amino acids Martinez-Force, Enrique; Benitez, Tahia Biotechnology Progress, Vol. 11, Issue 4 https://doi.org/10.1021/bp00034a004	journal	July 1995
Shifts in growth strategies reflect tradeoffs in cellular economics Molenaar, Douwe; van Berlo, Rogier; de Ridder, Dick Molecular Systems Biology, Vol. 5, Issue 1 https://doi.org/10.1038/msb.2009.82	journal	January 2009
Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast Zampar, Guillermo G.; Kümmel, Anne; Ewald, Jennifer Molecular Systems Biology, Vol. 9, Issue 1 https://doi.org/10.1038/msb.2013.11	journal	January 2013
Genome‐scale models of metabolism and gene expression extend and refine growth phenotype prediction O'Brien, Edward J.; Lerman, Joshua A.; Chang, Roger L. Molecular Systems Biology, Vol. 9, Issue 1 https://doi.org/10.1038/msb.2013.52	journal	January 2013
Overflow metabolism in Escherichia coli results from efficient proteome allocation Basan, Markus; Hui, Sheng; Okano, Hiroyuki Nature, Vol. 528, Issue 7580 https://doi.org/10.1038/nature15765	journal	December 2015
Fructose-1,6-bisphosphate couples glycolytic flux to activation of Ras Peeters, Ken; Van Leemputte, Frederik; Fischer, Baptiste Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/s41467-017-01019-z	journal	October 2017
A consensus S. cerevisiae metabolic model Yeast8 and its ecosystem for comprehensively probing cellular metabolism Lu, Hongzhong; Li, Feiran; Sánchez, Benjamín J. Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11581-3	journal	August 2019
A genome-scale metabolic model of Saccharomyces cerevisiae that integrates expression constraints and reaction thermodynamics Oftadeh, Omid; Salvy, Pierre; Masid, Maria Nature Communications, Vol. 12, Issue 1 https://doi.org/10.1038/s41467-021-25158-6	journal	August 2021
Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies Elsemman, Ibrahim E.; Rodriguez Prado, Angelica; Grigaitis, Pranas Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-28467-6	journal	February 2022
Proteome allocations change linearly with the specific growth rate of Saccharomyces cerevisiae under glucose limitation Xia, Jianye; Sánchez, Benjamin J.; Chen, Yu Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-30513-2	journal	May 2022
Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0 Domenzain, Iván; Sánchez, Benjamín; Anton, Mihail Nature Communications, Vol. 13, Issue 1 https://doi.org/10.1038/s41467-022-31421-1	journal	June 2022
Dynamic resource allocation drives growth under nitrogen starvation in eukaryotes Tibocha-Bonilla, Juan D.; Kumar, Manish; Richelle, Anne npj Systems Biology and Applications, Vol. 6, Issue 1 https://doi.org/10.1038/s41540-020-0135-y	journal	May 2020
An integrative circuit–host modelling framework for predicting synthetic gene network behaviours Liao, Chen; Blanchard, Andrew E.; Lu, Ting Nature Microbiology, Vol. 2, Issue 12 https://doi.org/10.1038/s41564-017-0022-5	journal	September 2017
An upper limit on Gibbs energy dissipation governs cellular metabolism Niebel, Bastian; Leupold, Simeon; Heinemann, Matthias Nature Metabolism, Vol. 1, Issue 1 https://doi.org/10.1038/s42255-018-0006-7	journal	January 2019
Metabolic Trade-offs in Yeast are Caused by F1F0-ATP synthase Nilsson, Avlant; Nielsen, Jens Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep22264	journal	March 2016
Resource allocation in living organisms Goelzer, Anne; Fromion, Vincent Biochemical Society Transactions, Vol. 45, Issue 4 https://doi.org/10.1042/BST20160436	journal	July 2017
Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry: Do we understand yeast glycolysis? Teusink, Bas; Passarge, Jutta; Reijenga, Corinne A. European Journal of Biochemistry, Vol. 267, Issue 17 https://doi.org/10.1046/j.1432-1327.2000.01527.x	journal	September 2000
Absolute yeast mitochondrial proteome quantification reveals trade-off between biosynthesis and energy generation during diauxic shift Di Bartolomeo, Francesca; Malina, Carl; Campbell, Kate Proceedings of the National Academy of Sciences, Vol. 117, Issue 13 https://doi.org/10.1073/pnas.1918216117	journal	March 2020
Proteome reallocation from amino acid biosynthesis to ribosomes enables yeast to grow faster in rich media Björkeroth, Johan; Campbell, Kate; Malina, Carl Proceedings of the National Academy of Sciences, Vol. 117, Issue 35 https://doi.org/10.1073/pnas.1921890117	journal	August 2020
Saccharomyces cerevisiae phenotypes can be predicted by using constraint-based analysis of a genome-scale reconstructed metabolic network Famili, I.; Forster, J.; Nielsen, J. Proceedings of the National Academy of Sciences, Vol. 100, Issue 23 https://doi.org/10.1073/pnas.2235812100	journal	October 2003
A Chemical Genomics Study Identifies Snf1 as a Repressor of GCN4 Translation Shirra, Margaret K.; McCartney, Rhonda R.; Zhang, Chao Journal of Biological Chemistry, Vol. 283, Issue 51 https://doi.org/10.1074/jbc.M805325200	journal	October 2008
The role of glycolysis-derived hexose phosphates in the induction of the Crabtree effect Rosas Lemus, Mónica; Roussarie, Elodie; Hammad, Noureddine Journal of Biological Chemistry, Vol. 293, Issue 33 https://doi.org/10.1074/jbc.RA118.003672	journal	August 2018
Comprehensive Temporal Protein Dynamics during the Diauxic Shift in Saccharomyces cerevisiae Murphy, J. Patrick; Stepanova, Ekaterina; Everley, Robert A. Molecular & Cellular Proteomics, Vol. 14, Issue 9 https://doi.org/10.1074/mcp.M114.045849	journal	September 2015
Growth-limiting Intracellular Metabolites in Yeast Growing under Diverse Nutrient Limitations Boer, Viktor M.; Crutchfield, Christopher A.; Bradley, Patrick H. Molecular Biology of the Cell, Vol. 21, Issue 1 https://doi.org/10.1091/mbc.e09-07-0597	journal	January 2010
Glucose repression in Saccharomyces cerevisiae Kayikci, Ömur; Nielsen, Jens FEMS Yeast Research, Vol. 15, Issue 6 https://doi.org/10.1093/femsyr/fov068	journal	July 2015
YMDB 2.0: a significantly expanded version of the yeast metabolome database Ramirez-Gaona, Miguel; Marcu, Ana; Pon, Allison Nucleic Acids Research, Vol. 45, Issue D1 https://doi.org/10.1093/nar/gkw1058	journal	November 2016
Genome-Scale Reconstruction of the Saccharomyces cerevisiae Metabolic Network Forster, J. Genome Research, Vol. 13, Issue 2 https://doi.org/10.1101/gr.234503	journal	February 2003
Nutrient sensing and signaling in the yeast Saccharomyces cerevisiae Conrad, Michaela; Schothorst, Joep; Kankipati, Harish Nag FEMS Microbiology Reviews, Vol. 38, Issue 2 https://doi.org/10.1111/1574-6976.12065	journal	March 2014
Characterization of glucose transport mutants ofSaccharomyces cerevisiaeduring a nutritional upshift reveals a correlation between metabolite levels and glycolytic flux Bosch, Daniel; Johansson, Mikael; Ferndahl, Cecilia FEMS Yeast Research, Vol. 8, Issue 1 https://doi.org/10.1111/j.1567-1364.2007.00323.x	journal	February 2008
Simple is good: yeast models of neurodegeneration Tenreiro, Sandra; Outeiro, Tiago Fleming FEMS Yeast Research, Vol. 10, Issue 8 https://doi.org/10.1111/j.1567-1364.2010.00649.x	journal	November 2010
A flux-sensing mechanism could regulate the switch between respiration and fermentation Huberts, Daphne H. E. W.; Niebel, Bastian; Heinemann, Matthias FEMS Yeast Research, Vol. 12, Issue 2 https://doi.org/10.1111/j.1567-1364.2011.00767.x	journal	December 2011
Interdependence of Cell Growth and Gene Expression: Origins and Consequences Scott, M.; Gunderson, C. W.; Mateescu, E. M. Science, Vol. 330, Issue 6007 https://doi.org/10.1126/science.1192588	journal	November 2010
Exploring the Metabolic and Genetic Control of Gene Expression on a Genomic Scale DeRisi, J. L.; Iyer, Vishwanath R.; Brown, Patrick O. Science, Vol. 278, Issue 5338, p. 680-686 https://doi.org/10.1126/science.278.5338.680	journal	October 1997
Systems-level analysis of mechanisms regulating yeast metabolic flux Hackett, S. R.; Zanotelli, V. R. T.; Xu, W. Science, Vol. 354, Issue 6311 https://doi.org/10.1126/science.aaf2786	journal	October 2016
Effect of Specific Growth Rate on Fermentative Capacity of Baker’s Yeast Van Hoek, Pim; Van Dijken, Johannes P.; Pronk, Jack T. Applied and Environmental Microbiology, Vol. 64, Issue 11 https://doi.org/10.1128/AEM.64.11.4226-4233.1998	journal	January 1998
A Minimal Set of Glycolytic Genes Reveals Strong Redundancies in Saccharomyces cerevisiae Central Metabolism Solis-Escalante, Daniel; Kuijpers, Niels G. A.; Barrajon-Simancas, Nuria Eukaryotic Cell, Vol. 14, Issue 8 https://doi.org/10.1128/EC.00064-15	journal	August 2015
Regulation of Amino Acid Transport in Saccharomyces cerevisiae Bianchi, Frans; van’t Klooster, Joury S.; Ruiz, Stephanie J. Microbiology and Molecular Biology Reviews, Vol. 83, Issue 4 https://doi.org/10.1128/MMBR.00024-19	journal	October 2019
Regulation of Sensing, Transportation, and Catabolism of Nitrogen Sources in Saccharomyces cerevisiae Zhang, Weiping; Du, Guocheng; Zhou, Jingwen Microbiology and Molecular Biology Reviews, Vol. 82, Issue 1 https://doi.org/10.1128/MMBR.00040-17	journal	February 2018
Glucose Signaling in Saccharomyces cerevisiae Santangelo, G. M. Microbiology and Molecular Biology Reviews, Vol. 70, Issue 1 https://doi.org/10.1128/MMBR.70.1.253-282.2006	journal	March 2006
Dynamic aspects of vacuolar and cytosolic amino acid pools of Saccharomyces cerevisiae. Kitamoto, K.; Yoshizawa, K.; Ohsumi, Y. Journal of Bacteriology, Vol. 170, Issue 6 https://doi.org/10.1128/jb.170.6.2683-2686.1988	journal	June 1988
The Crabtree Effect Shapes the Saccharomyces cerevisiae Lag Phase during the Switch between Different Carbon Sources Perez-Samper, Gemma; Cerulus, Bram; Jariani, Abbas mBio, Vol. 9, Issue 5 https://doi.org/10.1128/mBio.01331-18	journal	October 2018
How Saccharomyces Responds to Nutrients Zaman, Shadia; Lippman, Soyeon Im; Zhao, Xin Annual Review of Genetics, Vol. 42, Issue 1 https://doi.org/10.1146/annurev.genet.41.110306.130206	journal	December 2008
Role of cultivation media in the development of yeast strains for large scale industrial use Hahn-Hägerdal, Bärbel; Karhumaa, Kaisa; Larsson, Christer U. Microbial Cell Factories, Vol. 4, Issue 1 https://doi.org/10.1186/1475-2859-4-31	journal	November 2005
Adaptation of central metabolite pools to variations in growth rate and cultivation conditions in Saccharomyces cerevisiae Kumar, Kanhaiya; Venkatraman, Vishwesh; Bruheim, Per Microbial Cell Factories, Vol. 20, Issue 1 https://doi.org/10.1186/s12934-021-01557-8	journal	March 2021
Coordinated Concentration Changes of Transcripts and Metabolites in Saccharomyces cerevisiae Bradley, Patrick H.; Brauer, Matthew J.; Rabinowitz, Joshua D. PLoS Computational Biology, Vol. 5, Issue 1 https://doi.org/10.1371/journal.pcbi.1000270	journal	January 2009
Testing Biochemistry Revisited: How In Vivo Metabolism Can Be Understood from In Vitro Enzyme Kinetics van Eunen, Karen; Kiewiet, José A. L.; Westerhoff, Hans V. PLoS Computational Biology, Vol. 8, Issue 4 https://doi.org/10.1371/journal.pcbi.1002483	journal	April 2012
Comparative Analysis of Yeast Metabolic Network Models Highlights Progress, Opportunities for Metabolic Reconstruction Heavner, Benjamin D.; Price, Nathan D. PLOS Computational Biology, Vol. 11, Issue 11 https://doi.org/10.1371/journal.pcbi.1004530	journal	November 2015
Constrained Allocation Flux Balance Analysis Mori, Matteo; Hwa, Terence; Martin, Olivier C. PLOS Computational Biology, Vol. 12, Issue 6 https://doi.org/10.1371/journal.pcbi.1004913	journal	June 2016
Saccharomyces cerevisiae as a Model Organism: A Comparative Study Karathia, Hiren; Vilaprinyo, Ester; Sorribas, Albert PLoS ONE, Vol. 6, Issue 2 https://doi.org/10.1371/journal.pone.0016015	journal	February 2011
Improving the phenotype predictions of a yeast genome‐scale metabolic model by incorporating enzymatic constraints Sánchez, Benjamín J.; Zhang, Cheng; Nilsson, Avlant Molecular Systems Biology, Vol. 13, Issue 8 https://doi.org/10.15252/msb.20167411	journal	August 2017
Regulation of Amino Acid, Nucleotide, and Phosphate Metabolism in Saccharomyces cerevisiae Ljungdahl, Per O.; Daignan-Fornier, Bertrand Genetics, Vol. 190, Issue 3 https://doi.org/10.1534/genetics.111.133306	journal	March 2012
Nutritional Control of Growth and Development in Yeast Broach, James R. Genetics, Vol. 192, Issue 1 https://doi.org/10.1534/genetics.111.135731	journal	September 2012
Applications of Coarse-Grained Models in Metabolic Engineering Doan, Dieu Thi; Hoang, Manh Dat; Heins, Anna-Lena Frontiers in Molecular Biosciences, Vol. 9 https://doi.org/10.3389/fmolb.2022.806213	journal	March 2022
Yeast as a Tool for Deeper Understanding of Human Manganese-Related Diseases Thines, Louise; Deschamps, Antoine; Stribny, Jiri Genes, Vol. 10, Issue 7 https://doi.org/10.3390/genes10070545	journal	July 2019
AMPK Phosphorylation Is Controlled by Glucose Transport Rate in a PKA-Independent Manner Milanesi, Riccardo; Tripodi, Farida; Vertemara, Jacopo International Journal of Molecular Sciences, Vol. 22, Issue 17 https://doi.org/10.3390/ijms22179483	journal	August 2021
Kinetic Modeling of Saccharomyces cerevisiae Central Carbon Metabolism: Achievements, Limitations, and Opportunities Lao-Martil, David; Verhagen, Koen; Schmitz, Joep Metabolites, Vol. 12, Issue 1 https://doi.org/10.3390/metabo12010074	journal	January 2022
Saccharomyces cerevisiae and its industrial applications Parapouli, Maria; Vasileiadi, Anastasios; Afendra, Amalia-Sofia AIMS Microbiology, Vol. 6, Issue 1 https://doi.org/10.3934/microbiol.2020001	journal	January 2020
Transition between fermentation and respiration determines history-dependent behavior in fluctuating carbon sources Cerulus, Bram; Jariani, Abbas; Perez-Samper, Gemma eLife, Vol. 7 https://doi.org/10.7554/eLife.39234	journal	October 2018

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59 BASIC BIOLOGICAL SCIENCES
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