Cloning and characterization of beta-lactam biosynthetic genes.

Seven genes coding for two different enzymes of the penicillin/cephalosporin biosynthetic pathway have been cloned from fungal and bacterial sources. Using amino acid sequences derived from the purified enzymes, oligonucleotide probes were designed to hybridize to their cognate genes in a genomic library. The high degree of similarity (57%) between enzymes of bacterial and fungal origin suggests a horizontal transfer of a primordial beta-lactam pathway, probably from a bacterial cell to a fungal cell. Overproduction of the proteins in Escherichia coli has allowed further study of the mechanism of action of these important enzymes.