Molecular Regulation of the Penicillin Biosynthesis in Aspergillus nidulans

Axel A. Brakhage, Katharina Then Bergh and Olivier Litzka.

Author address: 

Lehrstuhl fur Mikrobiologie, Universitat Munchen, Maria-Ward-Str. la, D80638 Munchen, F.R.G.


The secondary metabolite penicillin is produced by some filamentous fungi only, most notably by Aspergillus nidulans and Penicillium chrysogenum. Starting from the three amino acid precursors, the penicillin biosynthesis is catalysed by three enzymes which are encoded by the following three genes: acvA (pcbAB), ipnA (pcbC) and aat (penDE). The genes are organised into a gene cluster. In A. nidulans, acvA and ipnA are bidirectionally transcribed. The aat gene lies 825 bps downstream of ipnA. Several regulatory circuits affecting the regulation of these penicillin biosynthesis genes have been identified. A moving window analysis of the 872-bp intergenic region between acvA and ipnA using reporter gene fusions indicated that the divergently orientated promoters are, at least in part, physically overlapping and share common regulatory elements. Removal of nucleotides -353 to -432 upstream of the acvA gene led to a 10-fold increase of acvA-uidA expression and simultaneously, to a reduction of ipnA-lacZ expression to about 30 %. Band shift assays and methyl interference analysis using partially purified protein extracts revealed that a short DNA element within this region was specifically bound by a protein (complex) which we designated PENR, for penicillin regulator. Deletion of 4 bps within the identified protein binding site caused the same contrary effects on acvA and ipnA expression, as observed for all of the deletion clones lacking nts -353 to -432. In addition, band shift assays and mutagenesis experiments led to the identification of a functional DNA element in the aat promoter region which was specifically bound by the same PENR protein (complex) as the intergenic region between acvA and ipnA. Hence, PENR seems to be involved in the regulation of all penicillin biosynthesis genes. Furthermore, the promoter regions of the corresponding genes of the -lactam producing fungi Penicillium ch sogenum and Acremonium chrysogenum also diluted the complex formed of the A. nidulans probes with PENR in vitro, suggesting that these -lactam biosynthesis genes are regulated by analogous DNA elements and proteins.

abstract No: 


Full conference title: 

    • ECFG 3rd (1996)