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

Science. 2002 Dec 20;298(5602):2390-2. doi: 10.1126/science.1077650.


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 acyl-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetate-CoA Ligase / chemistry
  • Acetate-CoA Ligase / genetics
  • Acetate-CoA Ligase / metabolism*
  • Acetylation
  • Acyl Coenzyme A / metabolism
  • Adenosine Monophosphate / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Coenzyme A / metabolism
  • Conserved Sequence
  • Enzyme Activation
  • Gene Expression Regulation, Bacterial
  • Immunoblotting
  • Lysine / metabolism*
  • Mass Spectrometry
  • NAD / metabolism
  • Peptide Mapping
  • Salmonella enterica / enzymology*
  • Salmonella enterica / genetics
  • Sirtuins / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Acyl Coenzyme A
  • Bacterial Proteins
  • NAD
  • propionyl-coenzyme A
  • Adenosine Monophosphate
  • Sirtuins
  • Acetate-CoA Ligase
  • Lysine
  • Coenzyme A