Slave nodes and the controllability of metabolic networks

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 few reactions in the network? This touches upon the issue of the number of degrees of freedom comprised 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 continuous 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 exhibit 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 reaction scan 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 window to study how the integrated dynamics of the entire metabolic network emerges from the coordinated behavior of its component parts. Journal-ref: New Journal of Physics 11, 113047 (2009). † Current address: Department of Applied Physics, Helsinki University of Technology, P.O. Box 5100, 02015 HUT, Finland Slave nodes and the controllability of metabolic networks 2