Design tradeoffs in a synthetic gene control circuit for metabolic networks

The performance of genetic control circuits for metabolism is subject to a number of tradeoffs that must be addressed at the design stage. We explore how the metabolic steady state and transient response depend on the regulatory topology and design parameters such as promoter and ribosome binding site strengths. We consider a one-to-all transcriptional control circuit for an unbranched metabolic pathway with saturable enzyme kinetics. The analysis highlights a compromise between operon and non-operon topologies in terms of robustness and design flexibility. We show that enzyme half-lives are an upper bound on the speed at which the pathway can adapt to a changing metabolic demand. We also analyze the destabilizing effect of basal enzyme expression and high regulatory sensitivity, albeit the latter reduces the steady state product bias.