Theory of circadian metabolism

TL;DR

This paper extends a proteome-growth framework to circadian metabolism, analyzing cyanobacteria's daily proteome reprogramming and storage strategies, revealing how circadian clocks optimize growth despite proteome relaxation constraints.

Contribution

It introduces a quantitative model linking circadian proteome dynamics to growth strategies in cyanobacteria, highlighting the role of circadian clocks in optimizing growth.

Findings

Cells grow mainly during the day to maximize 24-hour growth rate.

Slow proteome relaxation constrains optimal growth strategies.

Circadian clocks enable anticipation of environmental changes, improving growth.

Abstract

Many organisms repartition their proteome in a circadian fashion in response to the daily nutrient changes in their environment. A striking example is provided by cyanobacteria, which perform photosynthesis during the day to fix carbon. These organisms not only face the challenge of rewiring their proteome every 12 hours, but also the necessity of storing the fixed carbon in the form of glycogen to fuel processes during the night. In this manuscript, we extend the framework developed by Hwa and coworkers (Scott et al., Science 330, 1099 (2010)) for quantifying the relatinship between growth and proteome composition to circadian metabolism. We then apply this framework to investigate the circadian metabolism of the cyanobacterium Cyanothece, which not only fixes carbon during the day, but also nitrogen during the night, storing it in the polymer cyanophycin. Our analysis reveals that the need to store carbon and nitrogen tends to generate an extreme growth strategy, in which the cells predominantly grow during the day, as observed experimentally. This strategy maximizes the growth rate over 24 hours, and can be quantitatively understood by the bacterial growth laws. Our analysis also shows that the slow relaxation of the proteome, arising from the slow growth rate, puts a severe constraint on implementing this optimal strategy. Yet, the capacity to estimate the time of the day, enabled by the circadian clock, makes it possible to anticipate the daily changes in the environment and mount a response ahead of time. This significantly enhances the growth rate by counteracting the detrimental effects of the slow proteome relaxation.