Dynamic Metabolic Control

Bioprocessing technology offers a potentially promising and more sustainable alternative to many traditional chemical process technologies, however to date this potential has largely not been realized.The use of dynamic metabolic control strategies to engineer productive and robust stationary phase biocatalysts in combination with advanced two-stage fermentation has the potential to both increase process level metrics including specific productivity, volumetric rates and yields, while leveraging the unique ability of whole cell biocatalysts to perform multiple complex chemical conversions in a single step. Advances in Dynamic Metabolic Control can lead to a step change in the speed of engineering new biocatalysts and bioprocesses for the production of numerous molecules with a myriad of applications.

2-Stage Dynamic Metabolic Control

Dynamic Metabolic Control (DMC) in Two-Stage Bioprocesses. Top: A two-stage fermentation wherein Stage 1, biocatalyst generation is achieved through standard biomass growth. Upon entry into Stage 2 cells are triggered to switch into a catalytically active non-growing state enabling conversion of feedstock to product. Bottom: DMC can be used to convert the growing cells into productive stationary phase catalysts. DMC strategies can include inducible expression of heterologous production pathway enzymes (green) as well as increased activity of required native host enzymes (bold black). In addition, DMC allows for the controlled removal of competitive or inhibitory metabolic pathways (light gray), which can be accomplished via controlling transcription, translation of enzymes, or enzyme activities and levels post translationally (red).

Read some of our work related to Dynamic Metabolic Control :

Burg, JM.*, Cooper, CB.*, Ye, Z.*, Reed BR., Moreb, EA. and  Lynch, MD. "Large Scale Bioprocess Competitiveness: The Potential of Dynamic Metabolic Control in Two-Stage Fermentations" Current Opinion in Chemical Engineering 14 (2016): 121-136. *authors contributed equally to this work.

Lynch, MD. "Into new territory: improved microbial synthesis through engineering of the essential metabolic network." Current Opinion in Biotechnology 38 (2016): 106-111.