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.