Gene network requirements for regulation of metabolic gene expression to a desired state.

Gene circuits that control metabolism should restore metabolic functions upon environmental changes. Whether gene networks are capable of steering metabolism to optimal states is an open question. Here we present a method to identify such optimal gene networks. We show that metabolic network optimisation over a range of environments results in an input-output relationship for the gene network that guarantees optimal metabolic states. Optimal control is possible if the gene network can achieve this input-output relationship. We illustrate our approach with the best-studied regulatory network in yeast, the galactose network. We find that over the entire range of external galactose concentrations, the regulatory network is able to optimally steer galactose metabolism. Only a few gene network parameters affect this optimal regulation. The other parameters can be tuned independently for optimisation of other functions, such as fast and low-noise gene expression. This study highlights gene network plasticity, evolvability, and modular functionality.