title: BarR, an Lrp-type transcription factor in Sulfolobus acidocaldarius, regulates an aminotransferase gene in a β-alanine responsive manner.
abstract: In archaea, nothing is known about the β-alanine degradation pathway or its regulation. In this work, we identify and characterize BarR, a novel Lrp-like transcription factor and the first one that has a non-proteinogenic amino acid ligand. BarR is conserved in Sulfolobus acidocaldarius and Sulfolobus tokodaii and is located in a divergent operon with a gene predicted to encode β-alanine aminotransferase. Deletion of barR resulted in a reduced exponential growth rate in the presence of β-alanine. Furthermore, qRT-PCR and promoter activity assays demonstrated that BarR activates the expression of the adjacent aminotransferase gene, but only upon β-alanine supplementation. In contrast, auto-activation proved to be β-alanine independent. Heterologously produced BarR is an octamer in solution and forms a single complex by interacting with multiple sites in the 170 bp long intergenic region separating the divergently transcribed genes. In vitro, DNA binding is specifically responsive to β-alanine and site-mutant analyses indicated that β-alanine directly interacts with the ligand-binding pocket. Altogether, this work contributes to the growing body of evidence that in archaea, Lrp-like transcription factors have physiological roles that go beyond the regulation of α-amino acid metabolism.
authors.affiliation: Research Group of Microbiology, Department of Bio-engineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, B-1050, Brussels, Belgium.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.forename: Alvaro
authors.initials: A
authors.lastname: Orell
authors.forename: Dominique
authors.initials: D
authors.lastname: Maes
authors.forename: Marleen
authors.initials: M
authors.lastname: van Wolferen
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Lindås
authors.forename: Rolf
authors.initials: R
authors.lastname: Bernander
authors.forename: Sonja-Verena
authors.initials: SV
authors.lastname: Albers
authors.forename: Daniel
authors.initials: D
authors.lastname: Charlier
authors.forename: Eveline
authors.initials: E
authors.lastname: Peeters
mesh_terms: D004252:DNA Mutational Analysis; D019641:DNA, Archaeal / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D011485:Protein Binding; D055503:Protein Multimerization; D060888:Real-Time Polymerase Chain Reaction; D016945:Sulfolobus acidocaldarius / Q000235:genetics* / Q000378:metabolism*; D000637:Transaminases / Q000096:biosynthesis*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015091:beta-Alanine / Q000378:metabolism*
chemical_list: D019641:DNA, Archaeal; D014157:Transcription Factors; D015091:beta-Alanine; D000637:Transaminases