1.2. GNAT family in prokaryotes
The first two reported members of what is now termed the Gcn5- related N-acetyltransferases (GNATs) were the aminoglycoside N-acetyltransferase from multidrug-resistant Serratia marcescens and the histone acetyltransferase (HAT1) from Saccharomyces cerevisiae (Dutnall et al., 1998; Wolf et al., 1998). So far, GNATs comprise one of the largest enzyme superfamilies identified with more than 870 000 members through all kingdoms and more than 200 three-dimensional structures, mainly of bacteria, deposited in RCSB Protein Data Bank (PDB) (http://www.rcsb.org/pdb/home/home.do).
Bacteria and archaea present more annotated genes in the NCBI database than animals and plants, suggesting that the number of GNATs may be related to the environments inhabited by each organism and may reflect their metabolic complexity. For example, the genome of the nitrogen-fixing bacteria Rhizobium leguminosarum encodes 82 GNATs, the genome of the endophytic bacterium Pantoea agglomeransencodes 39 GNATs, the genome of the extremely halophilic archaeaHalapricum desulfuricans and Haloferax mediterraneiencoded 85 and 68 GNATs, respectively. These enzymes are involved in diverse cellular processes such as transcription control, antibiotic resistance, and stress regulation, among others (Salah et al., 2016; Xie et al., 2014). However, many GNATs still need to be characterized, so, their physiological role, substrate specificity, and structure of these enzymes are unknown.
GNAT members can acetylate the amino group of small molecules, metabolites, peptides, and proteins, with different implications (Table 1). The kinetically and structurally characterization of the aminoglycoside 6’-N-acetyltransferase from Enterococcus faeciumand Salmonella enterica showed that the enzyme can acetylate several aminoglycosides in solution. The presence of these proteins could be related to the increase of antibiotic resistance in some pathogen bacteria (Hegde et al., 2002; Magnet et al., 2001; Wright & Ladak,1997). The acetylation of the spermidine prevents polyamine toxicity at low temperatures and may play a similar physiological role in response to other stressful conditions (Limsuwun & Jones, 2000).
Interestingly, some acetyltransferases can acetylate different substrates; for example, the Eis protein from M. tuberculosis was initially described as an aminoglycoside acetyltransferase (Chen et al., 2011; Houghton et al., 2013; Zaunbrecher et al., 2009), but it also acetylates proteins (Ghosh et al., 2016; Kim et al., 2012). Both types of activities have different implications for the bacterium.