Characterization of a Penicillium chrysogenum gene encoding a PacC transcription factor and its binding sites in the divergent pcbAB-pcbC promoter of the penicillin biosynthetic cluster

Previous work established that pH regulation of gene expression in Aspergillus nidulans, a major determinant of penicillin biosynthesis, is mediated by the zinc-finger transcription factor PacC, an activator of transcription of the isopenicillin N synthase gene. We characterize here the pacC gene from the efficient penicillin producer Penicillium chrysogenum, which functionally complements an A. nidulans pacC null mutation. It encodes a 641-residue polypeptide showing 64% identity to A. nidulans PacC and containing three putative zinc fingers specifically recognizing a 5'-GCCARG-3' hexanucleotide. Penicillium pacC transcript levels are higher under alkaline than under acidic growth conditions and elevate at late stages of growth. The gene contains three PacC-binding sites in its 5'-upstream region. Transcript levels of pcbC (encoding P. chrysogenum isopenicillin N synthase) are low on a repressing carbon source and elevated on a derepressing carbon source. With either carbon source, alkaline pH elevates pcbC transcript levels, correlating with the presence of seven PacC-binding sites in the 1.1 kb pcbAB-pcbC intergenic region and strongly suggesting that pcbC is under direct pacC control. However, in contrast to the situation in A. nidulans, alkaline pH does not override the negative effects of a repressing carbon source, revealing differences in the regulation of the penicillin pathway between Penicillium and Aspergillus.