Lysine Acetylation Dynamics in Bacterial Proteins

Bacterial lysine acetylation is a reversible post-translational modification that regulates a multitude of cellular processes by altering protein structure, activity and interactions. Both enzymatic mechanisms—mediated by acetyltransferases of the GNAT superfamily—and non-enzymatic routes driven by metabolic intermediates such as acetyl phosphate contribute to the global acetylome. Dynamic acetylation of metabolic enzymes, ribosomal proteins and virulence factors enables bacteria to fine-tune central metabolism, control ribosome assembly and modulate pathogenicity in response to environmental or nutritional cues. Proteome-wide studies have revealed thousands of acetylation sites across diverse species, underscoring its ubiquity and evolutionary conservation. Structural and mechanistic insights into key acetyltransferase–substrate complexes and deacetylase regulation are beginning to clarify how the interplay between acetyl-CoA, acetyl phosphate and dedicated deacetylases shapes bacterial physiology and offers novel avenues for antimicrobial intervention.

Research from Nature Portfolio

Recent structural and biochemical work on Bacillus subtilis has elucidated how the GNAT-family acetyltransferase AcuA and the AMP-forming acetyl-CoA synthetase AcsA form a regulatory complex that dissociates upon lysine acetylation. High-resolution crystal structures of AcsA in apo and acetyl-AMP-bound forms, supported by AlphaFold2 predictions, reveal conformational changes in its C-terminal domain. Crucially, AcuA exhibits an intrinsic phosphotransacetylase activity, generating acetyl-CoA from acetyl phosphate and CoA to catalyse self-acetylation and inactivation of AcsA. This dual functionality provides a feedback mechanism that links cellular levels of acetyl phosphate and CoA to the dynamic regulation of central carbon flux via acetyl-CoA synthetase.

Lysine Acetylation Dynamics in Bacterial Proteins publication trend

The graph below shows the total number of articles in lysine acetylation dynamics in bacterial proteins across all publications each year (not limited to Nature Index journals).

Technical terms

Post-translational modification: A chemical alteration of a protein after its synthesis that regulates its activity, stability or localisation.

Lysine acetylation: The covalent addition of an acetyl group to the ε-amino group of a lysine residue, modulating protein charge and interactions.

Acetyltransferase: An enzyme that transfers an acetyl group from a donor molecule such as acetyl-CoA to a substrate protein.

Deacetylase: An enzyme that removes acetyl groups from lysine residues, reversing the modification.

Acetyl-CoA: A central metabolic intermediate that serves as an acetyl donor in enzymatic acetylation reactions.

Acetyl phosphate: A small-molecule metabolite capable of non-enzymatically transferring acetyl groups to lysine residues.

References

1. Acetyl-CoA synthetase activity is enzymatically regulated by lysine acetylation using acetyl-CoA or acetyl-phosphate as donor molecule. Nature Communications (2024).
2. Global profiling of ribosomal protein acetylation reveals essentiality of acetylation homeostasis in maintaining ribosome assembly and function. Nucleic Acids Research (2023).
3. CobB-mediated deacetylation of the chaperone CesA regulates Escherichia coli O157:H7 virulence. Gut Microbes (2024).
4. Functional and structural characterisation of RimL from Bacillus cereus, a new Nα-acetyltransferase of ribosomal proteins that was wrongly assigned as an aminoglycosyltransferase. International Journal of Biological Macromolecules (2024).
5. Mechanisms, Detection, and Relevance of Protein Acetylation in Prokaryotes. mBio (2019).