Gene organization and plasticity of the beta-lactam genes in different filamentous fungi

The genes pcbAB, pcbC and penDE encoding enzymes that catalyze the three st eps of the penicillin biosynthesis have been cloned from Penicillium chryso genum and Aspergillus nidulans. They are located in a cluster in Penicilliu m chrysogenum, Penicillium notatum, Aspergillus nidulans and Penicillium na lgiovense. The three genes are clustered in chromosome I (10.4 Mb) of P. ch rysogenum, in chromosome II of P. notatum (9.6 Mb) and in chromosome VI (3. 0 Mb) of A. nidulans. The cluster of the penicillin biosynthetic genes is a mplified in strains with high level of antibiotic production. About five to six copies of the cluster are present in the AS-P-78 strain and 11 to 14 c opies in the El strain tan industrial isolate), whereas only one copy is pr esent in the wild type (NRRL 1951) strain and in the low producer Wis 54-12 55 strain. The amplified region in strains AS-P-78 and El is arranged in ta ndem repeats of 106.5 or 57.6-kb units, respectively. In Acremonium chrysog enum the genes involved in cephalosporin biosynthesis are separated in at l east two clusters. The pcbAB and pcbC genes are linked in the so-called 'ea rly cluster' of genes involved in the cephalosporin biosynthesis. The 'late cluster', which includes the cefEF and cefG genes, is involved in the last steps of cephalosporin biosynthesis. The 'early cluster' was located in ch romosome VII (4.6 Mb) in the C10 strain and the 'late cluster' in chromosom e I (2.2 Mb). Both clusters are present in a single copy in the A. chrysoge num genome, in the wild-type and in the high cephalosporin-producing C10 st rains.