ampC Cephalosporinase of Escherichia coli K-12 Has a Different Evolutionary Origin from That of β -lactamases of the Penicillinase Type

A 1536-nucleotide-long sequence that carries the ampC β -lactamase gene of the Escherichia coli K-12 chromosome has been determined. This gene codes for a protein of 377 amino acids, of which the first 19 amino acids form a signal peptide. The molecular weight of the mature enzyme was determined to be 39,600. The ampC β -lactamase with a substrate specificity for cephalosporins showed no significant sequence homologies with β -lactamases of the penicillinase type or with D-alanine carboxy-peptidases. However, because the region around serine-80 of the ampC β -lactamase has extensive homology with an active-site fragment of the Pseudomonas aeruginosa cephalosporinase, we suggest that the ampC cephalosporinase as well as related cephalosporinases form a distinct group of serine β -lactamases that have an evolutionary origin different from that of the serine penicillinases and thus constitute a new class of β -lactamases.