Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine

V. J. Starai, I. Celic, R. N. Cole, J. D. Boeke, J. C. Escalante-Semerena

    Research output: Contribution to journalArticlepeer-review


    Acetyl-coenzyme A (CoA) synthetase (Acs) is an enzyme central to metabolism in prokaryotes and eukaryotes. Acs synthesizes acetyl CoA from acetate, adenosine triphosphate, and CoA through an acetyl-adenosine monophosphate (AMP) intermediate. Immunoblotting and mass spectrometry analysis showed that Salmonella enterica Acs enzyme activity is posttranslationally regulated by acetylation of lysine-609. Acetylation blocks synthesis of the adenylate intermediate but does not affect the thioester-forming activity of the enzyme. Activation of the acetylated enzyme requires the nicotinamide adenine dinucleotide-dependent protein deacetylase activity of the CobB Sir2 protein from S. enterica. We propose that acetylation modulates the activity of all the AMP-forming family of enzymes, including nonribosomal peptide synthetases, luciferase, and aryl- and aryl-CoA synthetases. These findings extend our knowledge of the roles of Sir2 proteins in gene silencing, chromosome stability, and cell aging and imply that lysine acetylation is a common regulatory mechanism in eukaryotes and prokaryotes.

    Original languageEnglish (US)
    Pages (from-to)2390-2392
    Number of pages3
    Issue number5602
    StatePublished - Dec 20 2002

    ASJC Scopus subject areas

    • General


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