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Abstract:
The operation of the central metabolism is typically assumed to be
deterministic, but dynamics and high connectivity of the metabolic
network make it potentially prone to generating fluctuations. However,
time-resolved measurements of metabolite levels in individual cells that
are required to characterize such fluctuations remained a challenge,
particularly in small bacterial cells. Here we use single-cell
metabolite measurements based on Forster resonance energy transfer,
combined with computer simulations, to explore the real-time dynamics of
the metabolic network of Escherichia coli. We observe that steplike
exposure of starved E. coli to glycolytic carbon sources elicits large
periodic fluctuations in the intracellular concentration of pyruvate in
individual cells. These fluctuations are consistent with predicted
oscillatory dynamics of E. coli metabolic network, and they are
primarily controlled by biochemical reactions around the pyruvate node.
Our results further indicate that fluctuations in glycolysis propagate
to other cellular processes, possibly leading to temporal heterogeneity
of cellular states within a population.
