ABSTRACT
It has been well recognized that regulation is a major hurdle to metabolic engineering. Various control loops are connected in multiple networks to direct metabolic ux in accordance with intracellular and extracellular conditions. As such, the cell is oen able to negate the alteration introduced by the metabolic engineer. Traditional metabolic engineering has focused on disrupting these regulatory loops and forcing the metabolic ux to a desired pathway regardless of the cell’s need. While this approach has enjoyed tremendous success, complex metabolic engineering may require sophicticated redesign of regulation networks, rather than eliminating them. In addition, building de novo regulatory loops may be necessary for foreign pathways to achieve higher yield and productivity. ese applications call for design of “synthetic” regulatory circuits that do not naturally exist in cells.
