Bifunctional Dynamic Control Network for Metabolic Engineering

Achieving viable productivities, titers and yields is extremely critical to microbial production. However, cellular and environmental changes may greatly impair microbial production due to that the producing hosts are incapable of responding to the changes dynamically. Thus, it is highly desired to develop dynamic control techniques to engineer cells with great biological robustness, which can automatically adjust their metabolic activities to the changing conditions to realize optimal production efficiency. In this presentation, we describe a general strategy for developing regulatory networks to implement dynamic controls of cellular metabolism for production improvement in microbial hosts. The regulatory elements consist of promoter, sensor-regulator, and antisense RNA. The dynamic regulation can occur at both transcriptional and post-transcriptional levels and involve not only heterologous genes but also host native metabolism.
More importantly, this dynamic regulation can execute orthogonal and simultaneous “up-regulation” and “downregulation” functions through using a single promoter-regulator system in response to the same inducing molecule, As a proof-of-concept, we utilize the muconic acid biosynthetic pathway developed in our group to examine the efficiency of this strategy on muconic acid production in Escherichia coli. Briefly, the research work involves the development and characterization of hybrid promoter-regulator system and dynamic regulatory network, and examination of the efficiency of dynamic regulatory network on muconic acid production.