The ddcA gene from Streptomyces fradiae encodes an extracellular beta-lactamase with penicillinase and cephalosporinase activities

The ddcA gene from Streptomyces fradiae, which is located adjacent to the l eft edge of the tylosin biosynthetic cluster, has been cloned and sequenced . DNA sequence analysis revealed an ORF of 1194 bp that encodes a product o f 42.6 kDa. This protein showed significant similarity to the extracellular endopeptidase with beta -lactamase activity encoded by the adp gene from B acillus cereus and to PBPs (DD-carboxypeptidases and DD-endopeptidases) and beta -lactamases. Moreover, it contains three characteristic motifs conser ved in PBPs and beta -lactamases, including an essential serine residue in the active centre and a putative leader peptide. Heterologous expression of the ddcA gene in Streptomyces lividans demonstrated the presence in the tr ansformants of an extracellular beta -lactamase active against penicillin G , ampicillin and the chromogenic cephalosporin nitrocefin. (C) 2000 Elsevie r Science B.V. All rights reserved.