Protein Kinase C (PkcA) of Aspergillus nidulans Is Involved in Penicillin Production

Abstract

The biosynthesis of the ␤-lactam antibiotic penicillin in the filamentous fungus Aspergillus nidulans is catalyzed by three enzymes that are encoded by the acvA, ipnA, and aatA genes. A variety of cis-acting DNA elements and regulatory factors form a complex regulatory network controlling these ␤-lactam biosynthesis genes. Regulators involved include the CCAAT-binding complex AnCF and AnBH1. AnBH1 acts as a repressor of the penicillin biosynthesis gene aatA. Until now, however, little information has been available on the signal transduction cascades leading to the transcription factors. Here we show that inhibition of protein kinase C (Pkc) activity in A. nidulans led to cytoplasmic localization of an AnBH1-enhanced green fluorescent protein (EGFP) fusion protein. Computer analysis of the genome and screening of an A. nidulans gene library revealed that the fungus possesses two putative Pkc-encoding genes, which we designated pkcA and pkcB. Only PkcA showed all the characteristic features of fungal Pkc's. Production of pkcA antisense RNA in A. nidulans led to reduced growth and conidiation in Aspergillus minimal medium, while in fermentation medium it led to enhanced expression of an aatAp-lacZ gene fusion, reduced pencillin production, and predominantly cytoplasmic localization of AnBH1. These data agree with the finding that inhibition of Pkc activity prevented nuclear localization of AnBH1-EGFP. As a result, repression of aatA expression was relieved. The involvement of Pkc in penicillin biosynthesis is also interesting in light of the fact that in the yeast Saccharomyces cerevisiae, Pkc plays a major role in maintaining cell integrity.

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

“…In N. crassa, PKC1 influences circadian rhythmicity and light response due to phosphorylation of the photoreceptor WC-1 (767,768). A. nidulans PkcA is involved in regulation of penicillin biosynthesis (769). Interestingly, in contrast to T. reesei, deletion of pkcA in A. nidulans is lethal.…”

Role of phospholipase C and protein kinase C in Aspergillus nidulans during growth on pectin or glucose: Effects on germination and duplication cycle

“…The second group, PLC-E, was seen in a wider range of fungi including some species of aspergilli and it is always found in a head-to-head arrangement with a copper oxidase, similar to the laccases. On the other hand, Pkc in Aspergillus nidulans is involved in cell wall integrity, penicillin production, polarized growth, and morphogenesis (Herrmann et al 2006;Teepe et al 2007;Ronen et al 2007). There are two putative Pkc-encoding genes in A. nidulans, which were designated pkcA and pkcB.…”

“…There are two putative Pkc-encoding genes in A. nidulans, which were designated pkcA and pkcB. The A. nidulans PkcA amino acid sequence contains an amino-terminal-extended regulatory domain, which has been found in fungal Pkcs only, and its amino acid sequence is characteristic of those of fungal Pkcs (Herrmann et al 2006). In PkcB, the regions of DAG or phorbol esters binding which are involved in the regulation of Pkc activity were not found (Azzi et al 1992).…”

Protein Kinase C of Filamentous Fungi and Its Roles in the Stresses Affecting Hyphal Morphogenesis and Conidiation

“…This growth defect was not remedied by the addition of osmotic stabilizers to the medium, which suggests that PkcA has other functions besides the function in the CWI signaling pathway (see following). It was reported that pkcA was involved in penicillin biosynthesis and was crucial for the nuclear localization of the transcription factor AnBH1 (Herrmann et al 2006 ).…”