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Design constraints in an operon circuit for engineered control of metabolic networks

We consider a synthetic gene circuit aimed at regulating the flux through an unbranched metabolic network. The control circuit has an operon architecture whereby the expression of all pathway enzymes is transcriptionally repressed by the metabolic product. We parameterize the gene regulatory model in terms of the promoter characteristic and ribosome binding site (RBS) strengths, both of which are common tuneable knobs in Synthetic Biology. We show that enzymatic saturation imposes bounds on the RBS strength design space. These bounds must be satisfied to prevent metabolite accumulation and guarantee the stability of the network. Simulation results also suggest that the control circuit can effectively upregulate enzyme production to compensate flux perturbations.