Abstract
β-lactams targeting the bacterial cell wall are not efficient on archaea. Using phylogenetic analysis and common ancestor sequences for bacterial β-lactamases, we found serendipitously class B and class C-like β-lactamase genes in most archaea genomes. The class B β-lactamase appears to be highly conserved in archaea and to has been transferred in the bacterial genus Elizabethkingia. The experimentaly expressed class B enzyme from Methanosarcina barkeri was able to digest penicillin G and was inhibited by a β-lactamase inhibitor (i.e. sulbactam). The class C-like β-lactamase was more closely related to DD-peptidase enzymes than know bacterial class C β-lactamases. The use of these very conserved genes in this domain cannot be explored as a defense system against β-lactams but may be used to feed β-lactams as a source of carbon as shown in bacteria.