Engineering ligand-specific biosensors for aromatic amino acids and neurochemicals

Austin G. Rottinghaus, Chenggang Xi, Matthew B. Amrofell, Hyojeong Yi, Tae Seok Moon

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Microbial biosensors have diverse applications in metabolic engineering and medicine. Specific and accurate quantification of chemical concentrations allows for adaptive regulation of enzymatic pathways and temporally precise expression of diagnostic reporters. Although biosensors should differentiate structurally similar ligands with distinct biological functions, such specific sensors are rarely found in nature and challenging to create. Using E. coli Nissle 1917, a generally regarded as safe microbe, we characterized two biosensor systems that promiscuously recognize aromatic amino acids or neurochemicals. To improve the sensors’ selectivity and sensitivity, we applied rational protein engineering by identifying and mutagenizing amino acid residues and successfully demonstrated the ligand-specific biosensors for phenylalanine, tyrosine, phenylethylamine, and tyramine. Additionally, our approach revealed insights into the uncharacterized structure of the FeaR regulator, including critical residues in ligand binding. These results lay the groundwork for developing kinetically adaptive microbes for diverse applications. A record of this paper's transparent peer review process is included in the supplemental information.

Original languageEnglish
Pages (from-to)204-214.e4
JournalCell Systems
Issue number3
StatePublished - Mar 16 2022


  • aromatic amino acid
  • aromatic neurochemical
  • directed evolution
  • probiotic
  • protein engineering
  • specific sensors


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