PT - JOURNAL ARTICLE AU - Jiefei Wang AU - Chao Zhang AU - W. Seth Childers TI - A Biosensor for Detection of Indole Metabolites AID - 10.1101/2021.03.05.434140 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.03.05.434140 4099 - http://biorxiv.org/content/early/2021/03/06/2021.03.05.434140.short 4100 - http://biorxiv.org/content/early/2021/03/06/2021.03.05.434140.full AB - The lack of diverse health-related biosensors limits the progress towards our understanding of how the microbiome metabolism impacts health. Microbially produced indole-3-aldehyde (I3A) has been associated with reducing inflammation in diseases such as ulcerative colitis by stimulating the aryl hydrocarbon receptor (AhR) pathway. We mined the protein database for gut microbiome metabolites’ sensors and developed a biosensor for I3A. We engineered E. coli embedded with a single plasmid carrying a chimeric two-component system that detects I3A. Our I3A receptor characterization identified residues that contribute to the sensor’s high specificity in a range of 0.1-10 µM. The I3A biosensor opens the door to sensing indole metabolites produced at the host-microbe interface and provides new parts for synthetic biology applications.Competing Interest StatementThe authors have declared no competing interest.5-HT5-hydroxytryptamineAhRAryl hydrocarbon receptorCACatalytic domainCNSCentral nervous systemDHpDimerization histidine phosphotransferDMSODMSO (Biological Grade)HKHistidine kinaseHtlDHTR-like protein DHTRHalobacterial transducer of rhodopsinI3AIndole-3-aldehydeI3AAIndole-3-acetic acidI3AM3-aminoindoleI3BAIndole-3-butyric acidI3M3-MethylindoleI3PAindole-3-pyruvic acidI3SP3-Indoxyl sulfateI5OH5-HydroxyindoleI7OH7-HydroxyindoleIACN3-IndolylacetonitrileIMI1-MethylindoleINDIndoleKanKanamycinKynKynurenineLBLuria-BertaniMKNMulti-kinase networkPASPer-Arnt-SimPDBProtein databaseRBSRibosomal binding siteRECReceiver domainRRResponse regulator