Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms
β-lactamase enzymes have generated significant interest due to their ability to confer resistance to the most commonly used family of antibiotics in human medicine. Among these enzymes, the class B β-lactamases are members of a superfamily of metallo-β-lactamase (MβL) fold proteins which are charact...
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2023-06-01
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author | Seydina M. Diene Pierre Pontarotti Saïd Azza Nicholas Armstrong Lucile Pinault Eric Chabrière Philippe Colson Jean-Marc Rolain Didier Raoult |
author_facet | Seydina M. Diene Pierre Pontarotti Saïd Azza Nicholas Armstrong Lucile Pinault Eric Chabrière Philippe Colson Jean-Marc Rolain Didier Raoult |
author_sort | Seydina M. Diene |
collection | DOAJ |
description | β-lactamase enzymes have generated significant interest due to their ability to confer resistance to the most commonly used family of antibiotics in human medicine. Among these enzymes, the class B β-lactamases are members of a superfamily of metallo-β-lactamase (MβL) fold proteins which are characterised by conserved motifs (i.e., HxHxDH) and are not only limited to bacteria. Indeed, as the result of several barriers, including low sequence similarity, default protein annotation, or untested enzymatic activity, MβL fold proteins have long been unexplored in other organisms. However, thanks to search approaches which are more sensitive compared to classical Blast analysis, such as the use of common ancestors to identify distant homologous sequences, we are now able to highlight their presence in different organisms including Bacteria, Archaea, Nanoarchaeota, Asgard, Humans, Giant viruses, and Candidate Phyla Radiation (CPR). These MβL fold proteins are multifunctional enzymes with diverse enzymatic or non-enzymatic activities of which, at least thirteen activities have been reported such as β-lactamase, ribonuclease, nuclease, glyoxalase, lactonase, phytase, ascorbic acid degradation, anti-cancer drug degradation, or membrane transport. In this review, we (i) discuss the existence of MβL fold enzymes in the different domains of life, (ii) present more suitable approaches to better investigating their homologous sequences in unsuspected sources, and (iii) report described MβL fold enzymes with demonstrated enzymatic or non-enzymatic activities. |
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spelling | doaj.art-464eda78315d4066afd272848405ebf82023-11-18T16:19:33ZengMDPI AGCells2073-44092023-06-011213175210.3390/cells12131752Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different OrganismsSeydina M. Diene0Pierre Pontarotti1Saïd Azza2Nicholas Armstrong3Lucile Pinault4Eric Chabrière5Philippe Colson6Jean-Marc Rolain7Didier Raoult8MEPHI, IRD, AP-HM, IHU-Méditerranée Infection, Aix Marseille University, 13005 Marseille, FranceMEPHI, IRD, AP-HM, IHU-Méditerranée Infection, Aix Marseille University, 13005 Marseille, FranceIHU-Méditerranée Infection, 13005 Marseille, FranceIHU-Méditerranée Infection, 13005 Marseille, FranceIHU-Méditerranée Infection, 13005 Marseille, FranceMEPHI, IRD, AP-HM, IHU-Méditerranée Infection, Aix Marseille University, 13005 Marseille, FranceMEPHI, IRD, AP-HM, IHU-Méditerranée Infection, Aix Marseille University, 13005 Marseille, FranceMEPHI, IRD, AP-HM, IHU-Méditerranée Infection, Aix Marseille University, 13005 Marseille, FranceIHU-Méditerranée Infection, 13005 Marseille, Franceβ-lactamase enzymes have generated significant interest due to their ability to confer resistance to the most commonly used family of antibiotics in human medicine. Among these enzymes, the class B β-lactamases are members of a superfamily of metallo-β-lactamase (MβL) fold proteins which are characterised by conserved motifs (i.e., HxHxDH) and are not only limited to bacteria. Indeed, as the result of several barriers, including low sequence similarity, default protein annotation, or untested enzymatic activity, MβL fold proteins have long been unexplored in other organisms. However, thanks to search approaches which are more sensitive compared to classical Blast analysis, such as the use of common ancestors to identify distant homologous sequences, we are now able to highlight their presence in different organisms including Bacteria, Archaea, Nanoarchaeota, Asgard, Humans, Giant viruses, and Candidate Phyla Radiation (CPR). These MβL fold proteins are multifunctional enzymes with diverse enzymatic or non-enzymatic activities of which, at least thirteen activities have been reported such as β-lactamase, ribonuclease, nuclease, glyoxalase, lactonase, phytase, ascorbic acid degradation, anti-cancer drug degradation, or membrane transport. In this review, we (i) discuss the existence of MβL fold enzymes in the different domains of life, (ii) present more suitable approaches to better investigating their homologous sequences in unsuspected sources, and (iii) report described MβL fold enzymes with demonstrated enzymatic or non-enzymatic activities.https://www.mdpi.com/2073-4409/12/13/1752metallo-β-lactamase (MβL) fold proteinsmultifunctional enzymesantibiotic-hydrolysing activitynucleaseribonucleaselactonase |
spellingShingle | Seydina M. Diene Pierre Pontarotti Saïd Azza Nicholas Armstrong Lucile Pinault Eric Chabrière Philippe Colson Jean-Marc Rolain Didier Raoult Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms Cells metallo-β-lactamase (MβL) fold proteins multifunctional enzymes antibiotic-hydrolysing activity nuclease ribonuclease lactonase |
title | Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms |
title_full | Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms |
title_fullStr | Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms |
title_full_unstemmed | Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms |
title_short | Origin, Diversity, and Multiple Roles of Enzymes with Metallo-β-Lactamase Fold from Different Organisms |
title_sort | origin diversity and multiple roles of enzymes with metallo β lactamase fold from different organisms |
topic | metallo-β-lactamase (MβL) fold proteins multifunctional enzymes antibiotic-hydrolysing activity nuclease ribonuclease lactonase |
url | https://www.mdpi.com/2073-4409/12/13/1752 |
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