Abstract
A time series of whole-genome transcription profiling of Escherichia
coli K-12 W3110 was performed during a carbon-limited fed-batch process.
The application of a constant feed rate led to the identification of a
dynamic sequence of diverse carbon limitation responses ( e. g., the
hunger response) and at the same time provided a global view of how
cellular and extracellular resources are used: the synthesis of
high-affinity transporters guarantees maximal glucose influx, thereby
preserving the phosphoenolpyruvate pool, and energy-dependent chemotaxis
is reduced in order to provide a more economic ``work mode.''
sigma(S)-mediated stress and starvation responses were both found to be
of only minor relevance. Thus, the experimental setup provided access to
the hunger response and enabled the differentiation of the hunger
response from the general starvation response. Our previous topological
model of the global regulation of the E. coli central carbon metabolism
through the crp, cra, and relA/spoT modulons is supported by correlating
transcript levels and metabolic fluxes and can now be extended. The
substrate is extensively oxidized in the tricarboxylic acid (TCA) cycle
to enhance energy generation. However, the general rate of oxidative
decarboxylation within the pentose phosphate pathway and the TCA cycle
is restricted to a minimum. Fine regulation of the carbon flux through
these pathways supplies sufficient precursors for biosyntheses. The
pools of at least three precursors are probably regulated through
activation of the (phosphoenolpyruvate-)glyoxylate shunt. The present
work shows that detailed understanding of the genetic regulation of
bacterial metabolism provides useful insights for manipulating the
carbon flux in technical production processes.
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