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

摘要

Summary Protein acetylation is a rapid mechanism for control of protein function. AcetylCoA synthetase (AMPforming, 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 theStreptomyces lividans Acs (Sl Acs) enzyme upon acetylation by PatB usingin vitro andin vivo analyses. In addition to the acetylation of residue K610, residue S608 within the acetylation motif ofSl Acs was also acetylated (PKTRSGK610 ). S608 acetylation renderedSl Acs inactive and nonacetylatable by PatB. It is unclear whether acetylation of S608 is enzymatic, but it was clear that this modification occurredin vivo inStreptomyces . InS. lividans , an NAD+ dependent sirtuin deacetylase fromStreptomyces , SrtA (a homologue of the human SIRT4 protein) was needed to maintainSl Acs functionin vivo . We have characterized a sirtuindependent reversible lysine acetylation system inStreptomyces 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 byO Ser andN[ Lys acetylation.