Molecular design of expression systems: Comparison of different control configurations using molecular mechanism models

Molecular-level mathematical models have been used to evaluate the effectiveness of eight different configurations of repressor synthesis control on the regulation of cloned gene expression initiated from a promoter-operator sequence. Both single and dual-repressor situations were considered, employing genetically structured models for the lac and lambdaP(R) promoter-operators in example calculations. Simulation results suggest that the most effective mode of cloned gene expression control is a cross-regulation configuration carried on a multicopy plasmid. This system was able to control cloned gene transcription in the uninduced state over a broad range of plasmid copy number and also provided the highest overall transcription rate in the induced state. The general strategies suggested by these simulations should be applicable for other repressor-operator-promoter systems in diverse hosts.