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

ABSTRACT

ß-lactam antibiotics have a well-known activity which disturbs the bacterial cell wall biosynthesis and may be cleaved by ß-lactamases. However, these drugs are not active on archaea microorganisms, which are naturally resistant because of the lack of ß-lactam target in their cell wall. Here, we describe that annotation of genes as ß-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, ß-lactamase, or glyoxalase, which may specialized over time. We expressed class B ß-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 ß-lactamase activity was inhibited by ß-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 ß-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 ß-lactamase enzymes and the specification of multipotent enzymes in different ways in Archaea and bacteria over time.