Manipulating the molecular specificity of transcriptional biosensors for tryptophan metabolites and analogs.

ABSTRACT: Tryptophan and its metabolites, produced by the gut microbiota, are pivotal for human physiological and mental health. Yet, quantifying these structurally similar compounds with high specificity remains a challenge, hindering point-of-care diagnostics and targeted therapeutic interventions. Leveraging the innate specificity and adaptability of biological systems, we present a biosensing approach capable of identifying specific metabolites in complex contexts with minimal cross-activity. This study introduces a generalizable strategy that combines evolutionary analysis, key ligand-binding residue identification, and mutagenesis scanning to pinpoint ligand-specific transcription factor variants. Furthermore, we uncover regulatory mechanisms within uncharacterized ligand-binding domains, whet

SUBMITTER: Xi C 

PROVIDER: S-EPMC11542736 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature