Cloning and Heterologous Expression of the Penicillin Biosynthetic Gene Cluster from Penicillium chrysogenum

A cosmid clone containing the putative penicillin biosynthetic gene cluster from Penicillium chrysogenum was used to transform the related filamentous fungi Neurospora crassa and Aspergillus niger, which do not produce β-lactam antibiotics. Both of the transformed hosts contained intact P. chrysogenum DNA derived from the cosmid clone and produced authentic penicillin V. Assays of penicillin biosynthetic enzyme activity additionally demonstrat ed that they possessed δ-(L-α-aminoadipyl)-L-cysteinyl D-valine synthetase (ACVS), isopenicillin N synthetase (IPNS) and acyl coenzyme A:6-aminopenicillanic acid acyltransferase (ACT) activity. The data suggests that genes encoding all the enzymes necessary for the biosynthesis of penicillin from amino acid precursors are closely linked in P. chrysogenum and constitute a gene cluster.