In Streptomyces lividans, acetyl-CoA synthetase activity is controlled by O-serine and N ɛ -lysine acetylation

Mol Microbiol. 2018 Feb;107(4):577-594. doi: 10.1111/mmi.13901. Epub 2018 Jan 18.

Abstract

Protein acetylation is a rapid mechanism for control of protein function. Acetyl-CoA synthetase (AMP-forming, Acs) is the paradigm for the control of metabolic enzymes by lysine acetylation. In many bacteria, type I or II protein acetyltransferases acetylate Acs, however, in actinomycetes type III protein acetyltransferases control the activity of Acs. We measured changes in the activity of the Streptomyces lividans Acs (SlAcs) enzyme upon acetylation by PatB using in vitro and in vivo analyses. In addition to the acetylation of residue K610, residue S608 within the acetylation motif of SlAcs was also acetylated (PKTRSGK610 ). S608 acetylation rendered SlAcs inactive and non-acetylatable by PatB. It is unclear whether acetylation of S608 is enzymatic, but it was clear that this modification occurred in vivo in Streptomyces. In S. lividans, an NAD+ -dependent sirtuin deacetylase from Streptomyces, SrtA (a homologue of the human SIRT4 protein) was needed to maintain SlAcs function in vivo. We have characterized a sirtuin-dependent reversible lysine acetylation system in Streptomyces lividans that targets and controls the Acs enzyme of this bacterium. These studies raise questions about acetyltransferase specificity, and describe the first Acs enzyme in any organism whose activity is modulated by O-Ser and Nɛ -Lys acetylation.

Publication types

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

MeSH terms

  • Acetate-CoA Ligase / genetics
  • Acetate-CoA Ligase / metabolism*
  • Acetyl Coenzyme A / metabolism*
  • Acetylation
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism
  • DNA, Bacterial / genetics
  • Gene Deletion
  • Group III Histone Deacetylases / genetics
  • Group III Histone Deacetylases / metabolism
  • Lysine / metabolism*
  • NAD / metabolism
  • Serine / metabolism*
  • Streptomyces lividans / enzymology*
  • Streptomyces lividans / genetics

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • NAD
  • Serine
  • Acetyl Coenzyme A
  • Acetyltransferases
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases
  • Group III Histone Deacetylases
  • Acetate-CoA Ligase
  • Lysine