Engineering Dynamic Control of Metabolic Pathways

The general strategy to optimize a production pathway is controlling expression levels of enzymes using variation of promoter strength of ribosome affinity. Choosing the optimal expression levels “a priori” is key for the performance of a heterologous production pathway, because the pathway usually lacks regulatory mechanisms and is not integrated with regulatory mechanisms of the host. However, without mechanisms like feedback regulation the production pathway cannot respond to the cells growth phase and any deviations away from optimal conditions might cause premature decrease of the production rate. Therefore, it is highly desirable to implement metabolic feedback regulation in a production pathway which drains the bulk of resources from the host. 

In this project we want to understand the consequences of removing regulation in native pathways and inserting heterologous pathways that are not under metabolic control. We seek for general design principles to integrate metabolism of the production host, the synthetic production pathway and the conditions of large-scale bioreactors. The ultimate goal is to create autonomous regulation of a synthetic production pathway and create strains that are robust and stable under industrial conditions.