Controlling metabolic flux by toehold-mediated strand displacement

To maximize desired products in engineered cellular factories it is often necessary to optimize metabolic flux. While a number of works have focused on metabolic pathway enhancement through genetic regulators and synthetic scaffolds, these approaches require time-intensive design and optimization with limited versatility and capacity for scale-up. Recently, nucleic-acid nanotechnology has emerged as an encouraging approach to overcome these limitations and create systems for modular programmable control of metabolic flux. Using toehold-mediated strand displacement (TMSD), nucleic acid constructs can be made into dynamic devices that recognize specific biomolecular triggers for conditional control of gene regulation as well as design of dynamic synthetic scaffolds. This review will consider the various approaches that have been used thus far to control metabolic flux using toehold-gated devices.