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.