Insights into the role of acetylation in Salmonella enterica
Hentchel, Kristy Lynn
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Protein and small molecule acetylation are widespread in nature. Acetylation can affect the function, activity, or stability of proteins, or alter the structure of small molecules. Acetylation provides an advantageous mechanism for altering activity of the target substrate, allowing for rapid alteration of physiology in response to environmental cues. Many of the enzymes catalyzing acetylation reactions belong to the Gcn5 N-acetyltransferase (GNAT) family. The majority of organisms encode around ~25 GNATs and the majority of these enzymes do not have known functions. In S. enterica, reversible lysine acetylation (RLA) of proteins is controlled by a GNAT (Pat) and a NAD+-dependent sirtuin deacetylase (CobB). RLA control is needed to modify the activity of the AMP-forming CoA ligases, such as the acetyl-CoA synthetase (Acs) enzyme that is required for growth in conditions containing acetate. The first portion of this work describes the identification of a transcriptional regulator, IolR, which activates expression of this system, and integrates the expression with that of the target substrate, Acs. This provided the first example of the acetylation / deacetylation system and its target being under the control the same transcriptional regulator. Only one protein acetyltransferase has been identified in S. enterica (Pat), and the majority of the characterized GNATs of S. enterica acetylate small molecule targets. The second portion of this work characterizes a subset of GNAT enzymes annotated as phosphinothricin acetyltransferases. These enzymes display varying specificity for phosphinothricin, or the closely related analogues methionine sulfoximine and methionine sulfone. This work provided information on how S. enterica and organisms respond to and detoxify harmful compounds present in the environment.