biostudies-literatureColson PAgence Nationale de la RechercheRégion Provence-Alpes-Côte d’Azur and Europe21685https://www.ebi.ac.uk/biostudies/studies/S-EPMC7729979biostudies-literatureUnknown10(1)Proteins with a metallo-beta-lactamase (MBL) fold have been largely studied in bacteria in the framework of resistance to beta-lactams, but their spectrum of activities is broader. We show here that the giant Tupanvirus also encodes a MBL fold-protein that has orthologs in other giant viruses, a deep phylogenetic root and is clustered with tRNases. This protein is significantly associated with translation components in giant viruses. After expression in Escherichia coli, it was found to hydrolyse nitrocefin, a beta-lactam, and penicillin G. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, the tupanvirus MBL fold-protein was not active on single- or double-stranded DNA, but degraded RNAs from bacteria and Acanthamoeba castellanii, the tupanvirus amoebal host. This aScientific reportsA protein of the metallo-hydrolase/oxidoreductase superfamily with both beta-lactamase and ribonuclease activity is linked with translation in giant viruses.PMC7729979Méditerranée-Infection 10-IAHU-03FEDER PA 0000320 PRIMMIColson PPinault LAzza SChabriere EPontarotti PArmstrong NRaoult DLa Scola BfalseA protein of the metallo-hydrolase/oxidoreductase superfamily with both beta-lactamase and ribonuclease activity is linked with translation in giant viruses.Proteins with a metallo-beta-lactamase (MBL) fold have been largely studied in bacteria in the framework of resistance to beta-lactams, but their spectrum of activities is broader. We show here that the giant Tupanvirus also encodes a MBL fold-protein that has orthologs in other giant viruses, a deep phylogenetic root and is clustered with tRNases. This protein is significantly associated with translation components in giant viruses. After expression in Escherichia coli, it was found to hydrolyse nitrocefin, a beta-lactam, and penicillin G. This was inhibited by sulbactam, a beta-lactamase inhibitor. In addition, the tupanvirus MBL fold-protein was not active on single- or double-stranded DNA, but degraded RNAs from bacteria and Acanthamoeba castellanii, the tupanvirus amoebal host. This a2020-01-01T00:00:00Z2020 Dec2025-04-19T14:02:05.51Z2021-02-20T11:33:19ZS-EPMC77299793330391910.1038/s41598-020-78658-8