Acetoacetyl-CoA synthetase activity is controlled by a protein acetyltransferase with unique domain organization in Streptomyces lividans

Mol Microbiol. 2013 Jan;87(1):152-67. doi: 10.1111/mmi.12088. Epub 2012 Nov 30.


GCN5-type N-acetyltransferases (GNATs) are enzymes that catalyse the transfer of the acetyl group from acetyl-CoA to a primary amine. GNATs are conserved in all domains of life. Some members of this family of enzymes acetylate the side-chain of specific lysine residues in proteins of diverse function. In bacteria, GNAT-catalysed protein acetylation regulates carbon metabolism, RNA metabolism and transcriptional regulation. Metabolic regulation in Streptomyces species is of interest due to the role of these organisms in natural product synthesis. Here we identify SlPatA, a GNAT in Streptomyces lividans with unique domain organization, and a new acetylation target, namely acetoacetyl-CoA synthetase (SlAacS). The latter has homologues in all domains of life. In vitro and in vivo evidence show that SlAacS is a bona fide acetoacetyl-CoA synthetase. SlPatA acetylates SlAacS more efficiently than it does acetyl-CoA synthetase, an enzyme known to be under acetylation control. SlPatA acetylates SlAacS at the active-site residue Lys617 and acetylation inactivates SlAacS. Acetylated SlAacS was deacetylated by a sirtuin-type protein deacetylase. SlAacS acetylation/deacetylation may represent a conserved mechanism for regulation of acetoacetyl-CoA synthetase activity in all domains of life.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Acetyltransferases / chemistry
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Amino Acid Sequence
  • Catalytic Domain
  • Coenzyme A Ligases / chemistry
  • Coenzyme A Ligases / genetics
  • Coenzyme A Ligases / metabolism*
  • Streptomyces lividans / enzymology*
  • Streptomyces lividans / genetics
  • Streptomyces lividans / metabolism


  • Acetyltransferases
  • protein acyltransferase
  • Coenzyme A Ligases
  • acetoacetyl-CoA synthetase