Engineering orthogonal signalling pathways reveals the sparse occupancy of sequence space.

ABSTRACT: Gene duplication is a common and powerful mechanism by which cells create new signalling pathways^1,2, but recently duplicated proteins typically must become insulated from each other and from other paralogues to prevent unwanted crosstalk³. A similar challenge arises when new sensors or synthetic signalling pathways are engineered within cells or transferred between genomes. How easily new pathways can be introduced into cells depends on the density and distribution of paralogous pathways in the sequence space that is defined by their specificity-determining residues^4,5. Here we directly investigate how crowded this sequence space is, by generating novel two-component signalling proteins in Escherichia coli using cell sorting coupled to deep sequencing to a

SUBMITTER: McClune CJ 

PROVIDER: S-EPMC6858568 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature