Abstract
## This item has been replaced by the one which can be found at [https://doi.org/10.7488/ds/7845] ## Biological rhythms not only coordinate cellular activity with external signals, but may also enable internal
coordination. The metabolic cycle in budding yeast is perhaps the most well-studied example. Historically
researchers have investigated this cycle in populations growing in chemostats, but more recently time-lapse
microscopy has revealed single-cell oscillations in the redox state of enzyme cofactors and in ATP levels.
How to relate the results of these two types of assays is however unclear. Here we report single-cell rhythms
too in intracellular pH and show that oscillations in the redox state of flavin molecules occur in auxotrophic
and prototrophic strains, in nutrients favouring respiration or fermentation, and in deletion mutants for
which oscillations in chemostats are either unobservable or disrupted. To explain the pervasiveness of
these rhythms, we postulate that cells generate oscillations to alleviate a proteome constraint – amino
acids cells use for one class of enzymes are unavailable for others. Using flux balance analysis with an
enzyme-constrained genome-scale metabolic model, we show that, with a finite proteome, sequential
synthesis of biomass components typically generates a shorter doubling time than synthesising components
in parallel. Our results suggest that the metabolic cycle drives growth and is potentially widespread because
all cells grow within a proteome constraint.
coordination. The metabolic cycle in budding yeast is perhaps the most well-studied example. Historically
researchers have investigated this cycle in populations growing in chemostats, but more recently time-lapse
microscopy has revealed single-cell oscillations in the redox state of enzyme cofactors and in ATP levels.
How to relate the results of these two types of assays is however unclear. Here we report single-cell rhythms
too in intracellular pH and show that oscillations in the redox state of flavin molecules occur in auxotrophic
and prototrophic strains, in nutrients favouring respiration or fermentation, and in deletion mutants for
which oscillations in chemostats are either unobservable or disrupted. To explain the pervasiveness of
these rhythms, we postulate that cells generate oscillations to alleviate a proteome constraint – amino
acids cells use for one class of enzymes are unavailable for others. Using flux balance analysis with an
enzyme-constrained genome-scale metabolic model, we show that, with a finite proteome, sequential
synthesis of biomass components typically generates a shorter doubling time than synthesising components
in parallel. Our results suggest that the metabolic cycle drives growth and is potentially widespread because
all cells grow within a proteome constraint.
| Date made available | 15 Nov 2024 |
|---|---|
| Publisher | Edinburgh DataShare |