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Science 20 December 2002:
Vol. 298. no. 5602, pp. 2390 - 2392
DOI: 10.1126/science.1077650
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Reports

Sir2-Dependent Activation of Acetyl-CoA Synthetase by Deacetylation of Active Lysine

V. J. Starai,1 I. Celic,2 R. N. Cole,3 J. D. Boeke,2 J. C. Escalante-Semerena1*

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.

1 Department of Bacteriology, University of Wisconsin, Madison, WI 53706-1567, USA.
2 Department of Molecular Biology and Genetics, and
3 Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA.
*   To whom correspondence should be addressed. E-mail: escalante{at}bact.wisc.edu

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