AAC(3)-XI,a New Aminoglycoside 3-N-Acetyltransferase from Corynebacterium striatum |
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| Authors: | Marc Galimand Jennifer Fishovitz Thierry Lambert Valérie Barbe Jaroslav Zajicek Shahriar Mobashery Patrice Courvalin |
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| Affiliation: | aInstitut Pasteur, Unité des Agents Antibactériens, Paris, France;bUniversity of Notre Dame, Notre Dame, Indiana, USA;cFaculté de Pharmacie, Université Paris Sud, Châtenay-Malabry, France;dC.E.A. Institut de Génomique-Genoscope, Laboratoire de Biologie Moléculaire pour l''Etude des Génomes (LBioMEG), Evry, France |
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| Abstract: | Corynebacterium striatum BM4687 was resistant to gentamicin and tobramycin but susceptible to kanamycin A and amikacin, a phenotype distinct among Gram-positive bacteria. Analysis of the entire genome of this strain did not detect any genes for known aminoglycoside resistance enzymes. Yet, annotation of the coding sequences identified 12 putative acetyltransferases or GCN5-related N-acetyltransferases. A total of 11 of these coding sequences were also present in the genomes of other Corynebacterium spp. The 12th coding sequence had 55 to 60% amino acid identity with acetyltransferases in Actinomycetales. The gene was cloned in Escherichia coli, where it conferred resistance to aminoglycosides by acetylation. The protein was purified to homogeneity, and its steady-state kinetic parameters were determined for dibekacin and kanamycin B. The product of the turnover of dibekacin was purified, and its structure was elucidated by high-field nuclear magnetic resonance (NMR), indicating transfer of the acetyl group to the amine at the C-3 position. Due to the unique profile of the reaction, it was designated aminoglycoside 3-N-acetyltransferase type XI. |
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