  Recent work on synthetic rescues has shown that the targeted deletion of
specific metabolic genes can often be used to rescue otherwise non-viable
mutants. This raises a fundamental biophysical question: to what extent can the
whole-cell behavior of a large metabolic network be controlled by constraining
the flux of one or more reactions in the network? This touches upon the issue
of the number of degrees of freedom contained by one such network. Using the
metabolic network of Escherichia coli as a model system, here we address this
question theoretically by exploring not only reaction deletions, but also a
continuum of all possible reaction expression levels. We show that the behavior
of the metabolic network can be largely manipulated by the pinned expression of
a single reaction. In particular, a relevant fraction of the metabolic
reactions exhibits canalizing interactions, in that the specification of one
reaction flux determines cellular growth as well as the fluxes of most other
reactions in optimal steady states. The activity of individual reactions can
thus be used as surrogates to monitor and possibly control cellular growth and
other whole-cell behaviors. In addition to its implications for the study of
control processes, our methodology provides a new approach to study how the
integrated dynamics of the entire metabolic network emerges from the
coordinated behavior of its component parts.
