Temporal segregation of biosynthetic processes is responsible for metabolic oscillations during the budding yeast cell cycle

Vakil Takhaveev, Serdar Özsezen, Edward N. Smith, Andre Zylstra, Marten L. Chaillet, Haoqi Chen, Alexandros Papagiannakis, Andreas Milias-Argeitis, Matthias Heinemann*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)
99 Downloads (Pure)

Abstract

Many cell biological and biochemical mechanisms controlling the fundamental process of eukaryotic cell division have been identified; however, the temporal dynamics of biosynthetic processes during the cell division cycle are still elusive. Here, we show that key biosynthetic processes are temporally segregated along the cell cycle. Using budding yeast as a model and single-cell methods to dynamically measure metabolic activity, we observe two peaks in protein synthesis, in the G1 and S/G2/M phase, whereas lipid and polysaccharide synthesis peaks only once, during the S/G2/M phase. Integrating the inferred biosynthetic rates into a thermodynamic-stoichiometric metabolic model, we find that this temporal segregation in biosynthetic processes causes flux changes in primary metabolism, with an acceleration of glucose-uptake flux in G1 and phase-shifted oscillations of oxygen and carbon dioxide exchanges. Through experimental validation of the model predictions, we demonstrate that primary metabolism oscillates with cell-cycle periodicity to satisfy the changing demands of biosynthetic processes exhibiting unexpected dynamics during the cell cycle.

Original languageEnglish
Pages (from-to)294-313
Number of pages20
JournalNature Metabolism
Volume5
Issue number2
DOIs
Publication statusPublished - 1-Feb-2023

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  • oLife Fellowship Programme

    Roos, W. (PI), van der Tak, F. (PI), Zijlstra, W. (PI), Dobos, V. (Postdoc), Heinen, L. (Postdoc), Thangaratnarajah, C. (Postdoc), Hoekzema, M. (Postdoc), Blokhuis, A. (Postdoc), Mascotti, L. (Postdoc), Padin Santos, D. (Postdoc), Chopra, A. (Postdoc), Obermaier, S. (Postdoc), Driver, M. (Postdoc), Moreira Goulart, M. (Postdoc), Sasidharan, S. (Postdoc), Samar Mahapatra, S. (Postdoc), Zylstra, A. (Postdoc), Geiger, Y. (Postdoc), Llopis Lorente, A. (Postdoc), Aschmann, D. (Postdoc) & Kulala Vittala, S. (Postdoc)

    01/04/201931/03/2024

    Project: Research

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