Expression of the Aspergilus nidulans penicillin biosynthesis genes acvA and ipnA, encoding 8-(L-aaminoadipyl)-L-cysteinyl-D-valine synthetase and isopenicillin N synthetase, respectively, was analyzed. The intergenic region carrying the divergently oriented promoters was fused in frame in both orientations to Escherichia coli lacZ and E. coli uidA4 reporter genes. Each construct permits simultaneous expression studies of both genes. Transformants of A. nidulans carrying a single copy of either plasmid integrated at the chromosomal argB locus were selected for further investigations. Expression of both genes was directed by the 872-bp intergenic region. ipnA-and acvA-derived gene fusions were expressed from this region at different levels. ipnA had significantly higher expression than did acvA. Glucose specifically reduced the production of penicillin and significantly repressed the expression of ipnA but not of acvA gene fusions. The specific activities of isopenicillin N synthetase, the gene product of ipnA, and acyl coenzyme A:6-aminopenicillanic acid acyltransferase were also reduced in glucose-grown cultures.The P-lactam antibiotic penicillin is synthesized by filamentous fungi of the genera Penicillium and Aspergillus (17, 32). It has been produced industrially by Penicillium chrysogenum for 50 years (20). Despite the worldwide usage of this antibiotic over a long period of time, little is known about the genetic regulation of its biosynthesis. This is in part because P. chrysogenum lacks a sexual cycle, and hence the genetics of this organism is poorly developed. In contrast, although producing only modest amounts of penicillin, Aspergillus nidulans, because of its sexual cycle, is well characterized genetically (12). A wide variety of genetic techniques are available, making identification of regulatory mechanisms feasible (2, 13, 51). The genetic system of A. nidulans permits manipulation of the genome with a high precision, providing an attractive model system in which to investigate genetic control of the biosynthesis of the secondary metabolite penicillin.In the first step of the penicillin biosynthetic pathway, the (5, 6, 11, 26, 31,

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