Dual RNase and β-lactamase Activity of a Single Enzyme Encoded in Archaea

Seydina M. Diene, Lucile Pinault, Nicholas Armstrong, Said Azza, Vivek Keshri, Saber Khelaifia, Eric Chabrière, Gustavo Caetano-Anolles, Jean Marc Rolain, Pierre Pontarotti, Didier Raoult

Research output: Contribution to journalArticlepeer-review


β-lactam antibiotics have a well-known activity which disturbs the bacterial cell wall biosynthesis and may be cleaved by β-lactamases. However, these drugs are not active on archaea microorganisms, which are naturally resistant because of the lack of β-lactam target in their cell wall. Here, we describe that annotation of genes as β-lactamases in Archaea on the basis of homologous genes is a remnant of identification of the original activities of this group of enzymes, which in fact have multiple functions, including nuclease, ribonuclease, β-lactamase, or glyoxalase, which may specialized over time. We expressed class B β-lactamase enzyme from Methanosarcina barkeri that digest penicillin G. Moreover, while weak glyoxalase activity was detected, a significant ribonuclease activity on bacterial and synthetic RNAs was demonstrated. The β-lactamase activity was inhibited by β-lactamase inhibitor (sulbactam), but its RNAse activity was not. This gene appears to have been transferred to the Flavobacteriaceae group especially the Elizabethkingia genus, in which the expressed gene shows a more specialized activity on thienamycin, but no glyoxalase activity. The expressed class C-like β-lactamase gene, from Methanosarcina sp., also shows hydrolysis activity on nitrocefin and is more closely related to DD-peptidase enzymes. Our findings highlight the need to redefine the nomenclature of β-lactamase enzymes and the specification of multipotent enzymes in different ways in Archaea and bacteria over time.

Original languageEnglish (US)
Article number280
Pages (from-to)1-12
Number of pages12
Issue number11
StatePublished - Nov 14 2020


  • Archaea
  • Common ancestor sequence
  • Core genes
  • Glyoxalases
  • Metallo-β-lactamases
  • Ribonucleases

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • General Biochemistry, Genetics and Molecular Biology
  • Space and Planetary Science
  • Palaeontology


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