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Abstract
Acetylation is a ubiquitous modification found in all domains of life. Acetyltransferase enzymes of the GCN5-N-acetyltransferase (GNAT) protein superfamily transfer an acetyl group to a protein or small molecule to modulate a variety of cellular processes, including transcription, translation, metabolism, and stress response. GNATs share little sequence homology, making it difficult to determine each protein’s target substrate, and thus physiological impact. Using the Gram-positive organisms Bacillus subtilis, Staphylococcus aureus, and Streptomyces lividans as model organisms, we elucidated the targets of a particular GNAT in each organism. In B. subtilis, the GNAT SatA acetylates and inactivates the antibiotic streptothricin. In the pathogen S. aureus, AcuA modulates the activity of the acetyl-Coenzyme A synthetase, which is needed for acetate metabolism. In S. lividans, novel acyl-Coenzyme A synthetase enzymes were characterized, some of which are regulated by the acetyltransferase PatB. Using genetic, biochemical, and structural approaches, this work helps frame acetylation in the larger context of cellular physiology.