Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies
Artikel i vetenskaplig tidskrift, 2022

When conditions change, unicellular organisms rewire their metabolism to sustain cell maintenance and cellular growth. Such rewiring may be understood as resource re-allocation under cellular constraints. Eukaryal cells contain metabolically active organelles such as mitochondria, competing for cytosolic space and resources, and the nature of the relevant cellular constraints remain to be determined for such cells. Here, we present a comprehensive metabolic model of the yeast cell, based on its full metabolic reaction network extended with protein synthesis and degradation reactions. The model predicts metabolic fluxes and corresponding protein expression by constraining compartment-specific protein pools and maximising growth rate. Comparing model predictions with quantitative experimental data suggests that under glucose limitation, a mitochondrial constraint limits growth at the onset of ethanol formation-known as the Crabtree effect. Under sugar excess, however, a constraint on total cytosolic volume dictates overflow metabolism. Our comprehensive model thus identifies condition-dependent and compartment-specific constraints that can explain metabolic strategies and protein expression profiles from growth rate optimisation, providing a framework to understand metabolic adaptation in eukaryal cells.

Författare

Ibrahim El-Semman

Danmarks Tekniske Universitet (DTU)

Assiut University

Angelica Rodriguez Prado

Vrije Universiteit Amsterdam

TU Delft

Pranas Grigaitis

Vrije Universiteit Amsterdam

Manuel Garcia

University of Manchester

Victoria Harman

University of Liverpool

Stephen W. Holman

University of Liverpool

Johan van Heerden

Vrije Universiteit Amsterdam

Frank J. Bruggeman

Vrije Universiteit Amsterdam

Mark Bisschops

TU Delft

N. Sonnenschein

Danmarks Tekniske Universitet (DTU)

Simon Hubbard

University of Manchester

Rob Beynon

University of Liverpool

P. Daran-Lapujade

TU Delft

Jens B Nielsen

Danmarks Tekniske Universitet (DTU)

Chalmers, Biologi och bioteknik, Systembiologi

B. Teusink

Vrije Universiteit Amsterdam

Nature Communications

2041-1723 (ISSN) 20411723 (eISSN)

Vol. 13 1 801

Ämneskategorier

Cellbiologi

Biokemi och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1038/s41467-022-28467-6

PubMed

35145105

Mer information

Senast uppdaterat

2022-02-24