Independent origins of subgroup Bl + B2 and subgroup B3 metallo-beta-lactamases.

The metallo-beta-lactamases constitute Class B in the Ambler classification of beta-lactamases and are divided into three subclasses: Bl, B2, and B3. Bayesian phylogenies of the Subclass B1 + B2 and Subclass B3 metallo-beta-lactamases and their homologs show that the beta-lactam-hydrolyzing function evolved independently within each group. In Subclass B1+B2 that function evolved about 1 billion years ago, and in Subclass B3 it evolved before the divergence of the Gram-positive and Gram-negative eubacteria, about 2 billion years ago. These results lend additional support to the proposal that the metallo-beta-lactamases should be divided into two distinct classes.