title: Directed evolution of the autoinducer selectivity of Vibrio fischeri LuxR.
abstract: LuxR family transcriptional regulators are the core components of quorum sensing in Gram-negative bacteria and exert their effects through binding to the signaling molecules acyl-homoserine lactones (acyl-HSLs). The function of the LuxR homologs is remarkably plastic, and naturally occurring acyl-HSLs are structurally diverse. To investigate the molecular basis of the functional plasticity of Vibrio fischeri LuxR, we directed the evolution of LuxR toward three different specificities in the laboratory. We found an orthogonal pair of LuxR mutants specific either to 3-oxo-hexanoyl homoserine lactone or to 3-oxo-octanoyl homoserine lactone. Interestingly, the majority of the specificity changes did not arise from modulating the recognition event but rather from changing the efficiency of the transition from the inactive form to the active form upon signal binding. This finding explains how quorum sensing systems can rapidly diverge in nature and in the laboratory and how signal orthogonality and mutual inhibition frequently occur among closely related diverging systems.
authors.affiliation: Department of Applied Chemistry and Biotechnology, Chiba University.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Tashiro
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kimura
authors.forename: Maiko
authors.initials: M
authors.lastname: Furubayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kei
authors.initials: K
authors.lastname: Terakubo
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Saito
authors.forename: Shigeko
authors.initials: S
authors.lastname: Kawai-Noma
authors.forename: Daisuke
authors.initials: D
authors.lastname: Umeno
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D048908:Aliivibrio fischeri / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D019020:Directed Molecular Evolution; D015964:Gene Expression Regulation, Bacterial; D016297:Mutagenesis, Site-Directed; D053038:Quorum Sensing / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D058615:Synthetic Biology / Q000379:methods; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins; C088386:homoserine lactone; D015107:4-Butyrolactone