REGULATION OF THE ASPERGILLUS-NIDULANS PENICILLIN BIOSYNTHESIS GENE ACVA (PCBAB) BY AMINO-ACIDS - IMPLICATION FOR INVOLVEMENT OF TRANSCRIPTION FACTOR PACC

The beta-lactam antibiotic penicillin is produced as an end product by some filamentous fungi only, It is synthesized from the amino acid pr ecursors L-alpha-aminoadipic acid, L-cysteine, and L-valine, Previous data suggested that certain amino acids play a role in the regulation of its biosynthesis. Therefore, in this study the effects of externall y added amino acids on both Aspergillus (Emericella) nidulans penicill in production and expression of the bidirectionally oriented biosynthe sis genes acvA (pcbAB) and ipnA (pcbC) were comprehensively investigat ed. Different effects caused by amino acids on the expression of penic illin biosynthesis genes and penicillin production were observed, Amin o acids with a major negative effect on the expression of acvA-uidA an d ipnA-lacZ gene fusions, i.e., histidine, valine, lysine, and methion ine, led to a decreased ambient pH during cultivation of the fungus. A n analysis of deletion clones lacking binding sites for the pH-depende nt transcriptional factor PACC in the intergenic regions between acvA- nidA and ipnA-lacZ gene fusions and in a pacC5 mutant (PacC5-5) sugges ted that the negative effects of histidine and valine on acvA-uidA exp ression were due to reduced activation by PACC under acidic conditions , These data also implied that PACC regulates the expression of acvA, predominantly through PACC binding site ipnA3. The repressing effect c aused by lysine and methionine on acvA expression, however, was even e nhanced in one of the deletion clones and the pacC5 mutant strain, sug gesting that regulators other than PACC are also involved.