A classic problem in microbiology is that bacteria display two types of growth behavior when cultured on a mixture of two carbon sources: the two sources are sequentially consumed one after another (diauxie) or they are simultaneously consumed (co-utilization). The search for the molecular mechanism of diauxie led to the discovery of the lac operon. However, questions remain as why microbes would bother to have different strategies of taking up nutrients. Here we show that diauxie versus co-utilization can be understood from the topological features of the metabolic network. A model of optimal allocation of protein resources quantitatively explains why and how the cell makes the choice. In case of co-utilization, the model predicts the percentage of each carbon source in supplying the amino acid pools, which is quantitatively verified by experiments. Our work solves a long-standing puzzle and provides a quantitative framework for the carbon source utilization of microbes.
The PhyB-PIF light-inducible dimerization system is used to achieve rapid, reversible, and titratable control of protein localization in budding yeast. This system can be used to dynamically activate or inactivate proteins of interest. It is used here to probe where and when Clb2 activity is required for nuclear fission and spindle stabilization.
Cell fate decisions are critical for life, yet little is known about how their
reliability is achieved when signals are noisy and fluctuating with time. In this
study, we show that in budding yeast, the decision of cell cycle commitment (Start)
is determined by the time integration of its triggering signal Cln3. We further
identify the Start repressor, Whi5, as the integrator. The instantaneous kinase
activity of Cln3-Cdk1 is recorded over time on the phosphorylated Whi5, and the
decision is made only when phosphorylated Whi5 reaches a threshold. Cells adjust the
threshold by modulating Whi5 concentration in different nutrient conditions to
coordinate growth and division. Our work shows that the strategy of signal
integration, which was previously found in decision-making behaviors of animals, is
adopted at the cellular level to reduce noise and minimize uncertainty.DOI:
http://dx.doi.org/10.7554/eLife.03977.001
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