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  • Title: Sirtuin-dependent reversible lysine acetylation of the o-succinylbenzoyl-coenzyme A synthetase of Bacillus subtilis.
    Author: Burckhardt RM, Escalante-Semerena JC.
    Journal: Microbiol Spectr; 2024 Oct 18; 12(12):e0201124. PubMed ID: 39422507.
    Abstract:
    Reversible lysine acylation (RLA) is a conserved posttranslational modification that cells of all domains of life use to regulate the biological function of proteins, some of which have enzymatic activity. Many AMP-forming organic acid:CoA ligases are regulated via acylation in prokaryotes and eukaryotes. Here, we report the acetylation of the o-succinylbenzoyl-CoA synthetase (EC 6.2.1.26) of Bacillus subtilis (BsMenE) by the GCN5-related acetyltransferase (GNAT) AcuA enzyme of this bacterium. BsMenE is part of the metabolic pathway that assembles menaquinone (MK), an essential component of the electron transport chain in B. subtilis. We demonstrate that the active-site lysine 471 (K471) of BsMenE is acetylated specifically by BsAcuA, and that acetylated BsMenE (BsMenEAc) is deacetylated by the NAD+-dependent sirtuin (BsSrtN) of this bacterium. The in vivo analyses performed in this study were done in an Escherichia coli ΔmenE strain because the enzymatic activity of MenE is essential in B. subtilis, but not in E. coli. The use of a heterologous system allowed us to assess the effect of acetylation on BsMenE function under MK-dependent growth conditions. Based on our in vivo data, we suggest that regulation of BsMenE by RLA reduces MK production, negatively affecting the growth rate and yield of the culture.IMPORTANCEReversible lysine acylation (RLA) is a posttranslational modification used by all cells to rapidly control the biological function of proteins. Herein, we identify an acetyltransferase and deacetylase in the soil bacterium Bacillus subtilis that can modify/demodify an enzyme required for the synthesis of menaquinone (MK), an essential electron carrier involved in respiration in cells of all domains of life. Based on our data, we suggest that under some as-yet-undefined physiological conditions, B. subtilis modulates MK biosynthesis, which changes the flux of electrons through the electron transport chain of this bacterium. To our knowledge, this is the first example of control of respiration by RLA.
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