Bacteria employ lysine acetylation of transcriptional regulators to adapt gene expression to cellular metabolism

Magdalena Kremer, Sabrina Schulze, Nadja Eisenbruch, Felix Nagel, Robert Vogt, Leona Berndt, Babett Dörre, Gottfried J. Palm, Jens Hoppen, Britta Girbardt, Dirk Albrecht, Susanne Sievers, Mihaela Delcea, Ulrich Baumann, Karin Schnetz and Michael Lammers ()
Additional contact information
Magdalena Kremer: University of Cologne
Sabrina Schulze: University of Greifswald
Nadja Eisenbruch: University of Greifswald
Felix Nagel: University of Greifswald
Robert Vogt: University of Greifswald
Leona Berndt: University of Greifswald
Babett Dörre: University of Greifswald
Gottfried J. Palm: University of Greifswald
Jens Hoppen: University of Greifswald
Britta Girbardt: University of Greifswald
Dirk Albrecht: University of Greifswald
Susanne Sievers: University of Greifswald
Mihaela Delcea: University of Greifswald
Ulrich Baumann: University of Cologne
Karin Schnetz: University of Cologne Zülpicher Straße 47a
Michael Lammers: University of Greifswald

Nature Communications, 2024, vol. 15, issue 1, 1-25

Abstract: Abstract The Escherichia coli TetR-related transcriptional regulator RutR is involved in the coordination of pyrimidine and purine metabolism. Here we report that lysine acetylation modulates RutR function. Applying the genetic code expansion concept, we produced site-specifically lysine-acetylated RutR proteins. The crystal structure of lysine-acetylated RutR reveals how acetylation switches off RutR-DNA-binding. We apply the genetic code expansion concept in E. coli in vivo revealing the consequences of RutR acetylation on the transcriptional level. We propose a model in which RutR acetylation follows different kinetic profiles either reacting non-enzymatically with acetyl-phosphate or enzymatically catalysed by the lysine acetyltransferases PatZ/YfiQ and YiaC. The NAD+-dependent sirtuin deacetylase CobB reverses enzymatic and non-enzymatic acetylation of RutR playing a dual regulatory and detoxifying role. By detecting cellular acetyl-CoA, NAD+ and acetyl-phosphate, bacteria apply lysine acetylation of transcriptional regulators to sense the cellular metabolic state directly adjusting gene expression to changing environmental conditions.

Date: 2024
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DOI: 10.1038/s41467-024-46039-8

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