Whole-cell modeling in yeast predicts compartment-specific proteome constraints that drive metabolic strategies

El-Semman, Ibrahim,1977Danmarks Tekniske Universitet,Technical University of Denmark,Assiut University (författare)

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.

Rodriguez Prado, AngelicaVrije Universiteit Amsterdam (VU),Technische Universiteit Delft,Delft University of Technology (TU Delft) (författare)
Grigaitis, PranasVrije Universiteit Amsterdam (VU) (författare)
Garcia, Manuel,1973University of Manchester(Swepub:cth)gmanuel (författare)
Harman, VictoriaUniversity of Liverpool (författare)
Holman, Stephen W.University of Liverpool (författare)
van Heerden, JohanVrije Universiteit Amsterdam (VU) (författare)
Bruggeman, Frank J.Vrije Universiteit Amsterdam (VU) (författare)
Bisschops, Mark,1985Technische Universiteit Delft,Delft University of Technology (TU Delft)(Swepub:cth)bishops (författare)
Sonnenschein, N.Danmarks Tekniske Universitet,Technical University of Denmark (författare)
Hubbard, SimonUniversity of Manchester (författare)
Beynon, RobUniversity of Liverpool (författare)
Daran-Lapujade, P.Technische Universiteit Delft,Delft University of Technology (TU Delft) (författare)
Nielsen, Jens B,1962Danmarks Tekniske Universitet,Technical University of Denmark,Chalmers tekniska högskola,Chalmers University of Technology(Swepub:cth)nielsenj (författare)
Teusink, B.Vrije Universiteit Amsterdam (VU) (författare)
Danmarks Tekniske UniversitetAssiut University (creator_code:org_t)

Ingår i:Nature Communications: Springer Science and Business Media LLC13:12041-17232041-1723

Av författaren/redakt...: El-Semman, Ibrah ...; Rodriguez Prado, ...; Grigaitis, Prana ...; Garcia, Manuel, ...; Harman, Victoria; Holman, Stephen ...; visa fler...; van Heerden, Joh ...; Bruggeman, Frank ...; Bisschops, Mark, ...; Sonnenschein, N.; Hubbard, Simon; Beynon, Rob; Daran-Lapujade, ...; Nielsen, Jens B, ...; Teusink, B.; visa färre...

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