Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans

Genomic clones containing an Aspergillus nidulans isopenicillin N synthetase (IPNS) gene have been identified by heterologous hybridization with a Cephalosporium acremonium DNA probe. The open reading frame encodes a 331 amino acid polypeptide with extensive homology with the genes of other beta-lactam-producing fungi. The gene product has been overexpressed in Escherichia coli and shown to have activity of IPNS. This represents the first evidence at the molecular level that the biosynthesis of penicillins in A. nidulans occurs by the same pathway as in other beta-lactam-producing microorganisms. Comparison of available nucleotide sequences from IPNS genes suggests a horizontal transmission of the gene between the prokaryotic beta-lactam producers of the genus Streptomyces and the filamentous fungi.