Ligify: Automated Genome Mining for Ligand-Inducible Transcription Factors

Prokaryotic transcription factors can be repurposed into
biosensors
for the ligand-inducible control of gene expression, but the landscape
of chemical ligands for which biosensors exist is extremely limited.
To expand this landscape, we developed Ligify, a web application that
leverages information in enzyme reaction databases to predict transcription
factors that may be responsive to user-defined chemicals. Candidate
transcription factors are then incorporated into automatically generated
plasmid sequences that are designed to express GFP in response to
the target chemical. Our benchmarking analyses demonstrated that Ligify
correctly predicted 31/100 previously validated biosensors and highlighted
strategies for further improvement. We then used Ligify to build a
panel of genetic circuits that could induce a 47-fold, 5-fold, 9-fold,
and 27-fold change in fluorescence in response to D-ribose, L-sorbose, isoeugenol, and 4-vinylphenol, respectively. Ligify
should enhance the ability of researchers to quickly develop biosensors
for an expanded range of chemicals and is publicly available at https://ligify.groov.bio.