Regulation, Function, and Detection of Protein Acetylation in Bacteria

Abstract

N -Lysine acetylation is now recognized as an abundant posttranslational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of acetylation events being rare in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely tuned via both enzymatic and nonenzymatic mechanisms. The opposing actions of Gcn5-related N-acetyltransferases (GNATs) and deacetylases, including sirtuins, provide the enzymatic control of lysine acetylation. A nonenzymatic mechanism of acetylation has also been demonstrated and proven to be prominent in bacteria, as well as in mitochondria. The functional consequences of the vast majority of the identified acetylation sites remain unknown. From studies in mammalian systems, acetylation of critical lysine residues was shown to impact protein function by altering its structure, subcellular localization, and interactions. It is becoming apparent that the same diversity of functions can be found in bacteria. Here, we review current knowledge of the mechanisms and the functional consequences of acetylation in bacteria. Additionally, we discuss the methods available for detecting acetylation sites, including quantitative mass spectrometry-based methods, which promise to promote this field of research. We conclude with possible future directions and broader implications of the study of protein acetylation in bacteria.

Characterizing lysine acetylation of Escherichia coli type II citrate synthase

“…SIRT3, a deacetylase, was shown to deacetylate and increase CS activity [8]. Although firstly discovered and extensively studied in eukaryotic histones and transcription-associated factors, lysine acetylation is also known to play important roles in bacterial physiology [9][10][11][12]. Acetylome studies have identified multiple lysine acetylation sites in the E. coli Type II CS [13], but their functions are still unknown.…”

Nε- and O-Acetylation in Mycobacterium tuberculosis Lineage 7 and Lineage 4 Strains: Proteins Involved in Bioenergetics, Virulence, and Antimicrobial Resistance Are Acetylated

“…62,63 Protein acetylation increases the net negative charge 62,64 on DNA binding proteins that might inhibit their binding capacity of the positively charged lysine residues with the negatively charged phosphate groups on DNA as reviewed by Carabetta et al 5 The inhibitory effect of acetylation on K residues found in the active sites of enzymes ACS, NhoA, adenosylmethionine synthase (MAT), and MbtA is highlighted in this review.…”

“…2–5 Increasing evidence supports the presence and role of lysine acetylation in mycobacteria. 6–12 In Mtb, lysine acetylation presumably confers protein stability and compartmentalization, thereby modulating diverse cellular processes.…”

“…Lysine acetylation is modulated via both enzymatic and nonenzymatic mechanisms (reviewed in ref 5). The enzymatic mechanism is regulated by the opposing actions of acetyltransferases and deacetylases.…”

Biological Effects and Properties of Eukaryotic Sirtuins

“…Активація сиртуїнів обмеженням калорій або за допомогою фармакологічних засобів продовжує тривалість життя і сприяє збереженню нормального перебігу процесів організмів − від дріжджів до ссавців. Це ще раз підкреслює доцільність розробки лікар-ських засобів, мішенню яких є сиртуїни, для терапії хвороб, опосередкованих старінням [9,10].…”