title: Gene network requirements for regulation of metabolic gene expression to a desired state.
abstract: 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.
authors.affiliation: Systems Bioinformatics, IBIVU, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Berkhout
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Bruggeman
mesh_terms: D018533:Biomass; D005690:Galactose / Q000378:metabolism; D015870:Gene Expression; D053263:Gene Regulatory Networks; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D005690:Galactose