TY  - JOUR
AU  - Qin, Chuan
AU  - Graf, Leonie G.
AU  - Striska, Kilian
AU  - Janetzky, Markus
AU  - Geist, Norman
AU  - Specht, Robin
AU  - Schulze, Sabrina
AU  - Palm, Gottfried
AU  - Girbardt, Britta
AU  - Dörre, Babett
AU  - Berndt, Leona
AU  - Kemnitz, Stefan
AU  - Doerr, Mark
AU  - Bornscheuer, Uwe T.
AU  - Delcea, Mihaela
AU  - Lammers, Michael
TI  - Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - PUBDB-2024-05684
SP  - 6002
PY  - 2024
N1  - German Research Foundation grant No. LA2984-6/1 and LA2984-8/1 (DFG, Deutsche Forschungsgemeinschaft).
AB  - The AMP-forming acetyl-CoA synthetase is regulated by lysine acetylation both in bacteria and eukaryotes. However, the underlying mechanism is poorly understood. The Bacillus subtilis acetyltransferase AcuA and the AMP-forming acetyl-CoA synthetase AcsA form an AcuA•AcsA complex, dissociating upon lysine acetylation of AcsA by AcuA. Crystal structures of AcsA from Chloroflexota bacterium in the apo form and in complex with acetyl-adenosine-5′-monophosphate (acetyl-AMP) support the flexible C-terminal domain adopting different conformations. AlphaFold2 predictions suggest binding of AcuA stabilizes AcsA in an undescribed conformation. We show the AcuA•AcsA complex dissociates upon acetyl-coenzyme A (acetyl-CoA) dependent acetylation of AcsA by AcuA. We discover an intrinsic phosphotransacetylase activity enabling AcuA•AcsA generating acetyl-CoA from acetyl-phosphate (AcP) and coenzyme A (CoA) used by AcuA to acetylate and inactivate AcsA. Here, we provide mechanistic insights into the regulation of AMP-forming acetyl-CoA synthetases by lysine acetylation and discover an intrinsic phosphotransacetylase allowing modulation of its activity based on AcP and CoA levels.
LB  - PUB:(DE-HGF)16
C6  - pmid:39019872
UR  - <Go to ISI:>//WOS:001272173500031
DO  - DOI:10.1038/s41467-024-49952-0
UR  - https://bib-pubdb1.desy.de/record/613905
ER  -