Introduction
Unlike the human genome, whose total length is approximately 6.2 Gbp in which only 3% encode approximately 20,000 proteins, bacteria have smaller genome (<0.5 to 10 Mbp) encoding only 1,500-7,500 proteins (Fredens et al., 2019; Piovesan et al., 2019). Even with such a low number of proteins, microorganisms can carry out complex cellular functions by increasing the functional diversity of proteins through post-translational modifications (PTMs).
Post-translational modifications are covalent and generally enzymatic modifications of amino acid residues in a protein after the synthesis of the polypeptide chain. The modifications of the amino acid side chains range from small chemical groups (e.g., methylation, acetylation, and phosphorylation), to more complex modifications such as the addition of oligosaccharides or small peptides (e.g., glycosylation and ubiquitylation) (Heuts et al., 2009; Macek et al., 2019; Mann & Jensen, 2003). Through protein PTMs, cells regulate their functions and metabolic pathways and increase the variety and complexity of target proteins. The PTMs most widely distributed and frequently reported are phosphorylation, glycosylation, ubiquitination, methylation, and acetylation, among other types of alkylations. (Khoury et al., 2011).
A wide variety of amino acid residues are susceptible to post-translational modification. In particular, the epsilon amino group of the side chain of lysine residues is the target of many of these modifications, including acetylation (Gil et al., 2017). Based on the acetylation site in the protein, three different types have been described:
(1) The irreversible acetylation of the alpha-amino group in the N-terminal amino acid of proteins (Nα-acetylation), a common modification in eukaryotes (50-70% of yeast proteins and 80-90% of human proteins).
(2) The reversible acetylation of the hydroxyl side chain of serine or threonine (O-acetylation), is detected only in a few eukaryotic organisms.
(3) The reversible acetylation of the epsilon-amino group of the lysine residue (Nɛ-acetylation). The Nα- and Nɛ-acetylation may occur on different amino acids residues (Lys, Ala, Arg, among others) with different frequencies, being the acetylation of lysine residues the most reported (Diallo et al., 2019; Khoury et al., 2011; Ramazi & Javad Zahiri, 2021).
Nɛ-acetylation occurs through two distinct mechanisms: enzymatic by the lysine acetyltransferases (KATs) and non-enzymatic (by chemical acetylation). In both cases, the acetyl group from a donor molecule, typically in the form of acetyl coenzyme A (AcCoA) or acetyl phosphate (AcP), is transferred to a target lysine residue. Both types of acetylation are reversible by the action of deacetylase enzymes (Figure 1A) (Hentchel & Escalante-Semerena, 2015).
The acetylation of lysine residues was discovered more than 50 years ago in histones and was linked to the regulation of transcription (Allfrey et al., 1964). Extensive studies in eukaryotic cells have shown that acetylation is an essential protein modification that influences many cellular processes, including protein-protein interaction, protein stability, protein folding, cellular localization, and enzymatic activity. Also, this PTM regulated different biological pathways, such as cell cycle control, cell metabolism, DNA repair, DNA replication, ribosome biogenesis in the nucleus, nuclear transport, translation, and transcription, among others. (Berrabah et al., 2011; Gil et al., 2017; Oliveira & Sauer, 2012; Tarazona & Pourquié, 2020). In contrast, research on acetylation in prokaryotes is relatively new, primarily focused on describing global acetylation through a proteomic approach. From these studies, it has been found that in some bacteria, the acetylated proteins on lysine constitute more than 10% of the proteome. This PTM influences several fundamental cellular pathways, including cellular function, cellular differentiation, and bacterial metabolism.