Bacterial sirtuin CobB and PRPP synthase crosstalk in regulation of protein acetylation

Abstract Protein lysine acetylation, regulates a wide range of cellular functions and is controlled by protein deacetylases called sirtuins. In eukaryotes, sirtuins activity is coupled to the spatiotemporally-controlled NAD+ level. However, regulation of the bacterial sirtuin CobB and its coupling to the NAD+ metabolism is not well understood. In this work we show that such coordination in Escherichia coli cells is achieved through a CobB interaction with PRPP synthase Prs, an enzyme necessary for NAD+ synthesis. Probing CobB protein-protein interactions, we demonstrate that it forms a stable complex with Prs. This assembly stimulates CobB deacetylase activity and partially protects it from inhibition by nicotinamide. We provide evidence that Prs acetylation is not necessary for CobB binding but affects the global acetylome and CobB activity in vivo . Consequently, we show that Prs acetylation status affects bacterial growth under different metabolic regimes. Therefore, we propose that CobB-Prs crosstalk orchestrates the NAD+ metabolism and protein acetylation in response to environmental cues.