BarR, an Lrp-type transcription factor in sulfolobus acidocaldarius, regulates an aminotransferase gene in a Î²-alanine responsive manner.
Liu, Han [Vrije Universiteit Brussel. Research Group of Microbiology, Department of Bio-engineering Sciences]
Peeters, Eveline [Chile. Universidad Mayor. Centro de Genómica y Bioinformática]
Charlier, Daniel [Vrije Universiteit Brussel. Research Group of Microbiology, Department of Bio-engineering Sciences]
Albers, Sonja‐Verena [Max Planck Institute for Terrestrial Microbiology]
Bernander,Rolf [Stockholm University]
Ann‐Christin, Lindås [Stockholm University]
van Wolferen, Marleen [Max Planck Institute for Terrestrial Microbiology]
Maes, Dominique [Vrije Universiteit Brussel. Research Group of Microbiology, Department of Bio-engineering Sciences]
Orell, Alvaro [Max Planck Institute for Terrestrial Microbiology]
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.
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