Macrolide Biosensor Optimization through Cellular Substrate Sequestration.

ABSTRACT: Developing and optimizing small-molecule biosensors is a central goal of synthetic biology. Here we incorporate additional cellular components to improve biosensor sensitivity by preventing target molecules from diffusing out of cells. We demonstrate that trapping erythromycin within Escherichia coli through phosphorylation increases the sensitivity of its biosensor (MphR) by approximately 10-fold. When combined with prior engineering efforts, our optimized biosensor can detect erythromycin concentrations as low as 13 nM. We show that this strategy works with a range of macrolide substrates, enabling the potential usage of our optimized system for drug development and metabolic engineering. This strategy can be extended in future studies to improve the sensitivity of other biosensor

SUBMITTER: Miller CA 

PROVIDER: S-EPMC7901672 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature