Structure and mechanism of potent bifunctional β-lactam- and homoserine lactone-degrading enzymes from marine microorganisms.

Autor: Selleck C; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Pedroso MM; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.pedroso@uq.edu.au.; Australian Centre for Ecogenomics, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.pedroso@uq.edu.au.; Sustainable Minerals Institute, The University of Queensland, St. Lucia, QLD, 4072, Australia. m.pedroso@uq.edu.au., Wilson L; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Krco S; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Knaven EG; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Miraula M; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia.; Department of Chemistry, Maynooth University, Maynooth, County Kildare, Ireland., Mitić N; Department of Chemistry, Maynooth University, Maynooth, County Kildare, Ireland., Larrabee JA; Department of Chemistry and Biochemistry, Middlebury College, Middlebury, VT, 05753, USA., Brück T; Werner Siemens Chair of Synthetic Biotechnology, Department of Chemistry, Technical University of Munich (TUM), Lichtenberg Str. 4, 85748, Garching, Germany., Clark A; Sustainable Minerals Institute, The University of Queensland, St. Lucia, QLD, 4072, Australia., Guddat LW; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia., Schenk G; School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, 4072, Australia. schenk@uq.edu.au.; Australian Centre for Ecogenomics, The University of Queensland, St. Lucia, QLD, 4072, Australia. schenk@uq.edu.au.; Sustainable Minerals Institute, The University of Queensland, St. Lucia, QLD, 4072, Australia. schenk@uq.edu.au.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Jul 30; Vol. 10 (1), pp. 12882. Date of Electronic Publication: 2020 Jul 30.
DOI: 10.1038/s41598-020-68612-z
Abstrakt: Genes that confer antibiotic resistance can rapidly be disseminated from one microorganism to another by mobile genetic elements, thus transferring resistance to previously susceptible bacterial strains. The misuse of antibiotics in health care and agriculture has provided a powerful evolutionary pressure to accelerate the spread of resistance genes, including those encoding β-lactamases. These are enzymes that are highly efficient in inactivating most of the commonly used β-lactam antibiotics. However, genes that confer antibiotic resistance are not only associated with pathogenic microorganisms, but are also found in non-pathogenic (i.e. environmental) microorganisms. Two recent examples are metal-dependent β-lactamases (MBLs) from the marine organisms Novosphingobium pentaromativorans and Simiduia agarivorans. Previous studies have demonstrated that their β-lactamase activity is comparable to those of well-known MBLs from pathogenic sources (e.g. NDM-1, AIM-1) but that they also possess efficient lactonase activity, an activity associated with quorum sensing. Here, we probed the structure and mechanism of these two enzymes using crystallographic, spectroscopic and fast kinetics techniques. Despite highly conserved active sites both enzymes demonstrate significant variations in their reaction mechanisms, highlighting both the extraordinary ability of MBLs to adapt to changing environmental conditions and the rather promiscuous acceptance of diverse substrates by these enzymes.
Databáze: MEDLINE
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