SUPERSEDED - Single-cell metabolic oscillations are pervasive and may alleviate a proteome constraint

## This item has been replaced by the one which can be found at [https://doi.org/10.7488/ds/7845] ## Biological rhythms not only coordinate cellular activity with external signals, but may also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 internalcoordination. The metabolic cycle in budding yeast is perhaps the most well-studied example. Historicallyresearchers have investigated this cycle in populations growing in chemostats, but more recently time-lapsemicroscopy 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 rhythmstoo in intracellular pH and show that oscillations in the redox state of flavin molecules occur in auxotrophicand prototrophic strains, in nutrients favouring respiration or fermentation, and in deletion mutants forwhich oscillations in chemostats are either unobservable or disrupted. To explain the pervasiveness ofthese rhythms, we postulate that cells generate oscillations to alleviate a proteome constraint – aminoacids cells use for one class of enzymes are unavailable for others. Using flux balance analysis with anenzyme-constrained genome-scale metabolic model, we show that, with a finite proteome, sequentialsynthesis of biomass components typically generates a shorter doubling time than synthesising componentsin parallel. Our results suggest that the metabolic cycle drives growth and is potentially widespread becauseall cells grow within a proteome constraint.