Dynamic metabolic control using synthetic metabolic valves in two-stage fermentations

We have developed a robust and generalizable two-stage system, which decouples microbial growth and metabolic production. Metabolic flux is effectively redirected from growth to production by synthetic metabolic “valves” using a combination of controlled protein degradation and gene silencing, in a phosphate limited stationary phase. The approach offers the potential of standardized fermentation processes independent of the products to be made. The two-stage system was systematically compared to traditional growth associated production using several products and combinatorial pathway libraries. We have demonstrated rapid and impressive improvements in production rate, titer and yield for several chemical products using our two-stage system.