Glukoseregulation der Cephalosporin C-Biosynthese im Hyphenpilz Acremonium chrysogenum
The 13-lactam antibiotic cephalosporin C is of great importance in pharmaceutical applications. The present work includes the first investigation of the cephalosporin C biosynthesis regulation by glucose on the molecular level in different strains of the filamentous fungus Acremonium chrysogenum. Hereby, interest has been focussed on the effect of glucose on the expression of the biosynthesis genes pcbC, cefEF and cefG.
Furthermore, the transcription factor CREA from A. chrysogenum has been isolated and its involvement in cephalosporin C biosynthesis regulation by glucose has been analyzed. The following results can be summarized: 5) By transforming A. chrysogenum A3/2 with additional copies of the creA gene, a wild-type-like transcriptional repression of the previously derepressed pcbC gene could be achieved. Simultaneously, the transcriptional repression of cefEF was increased. These findings suggest an involvement of CREA in the glucose regulation of these genes.
A model of CREA function is given. The results of this work prove that glucose is an important factor in the negative regulation of the cephalosporin C biosynthesis in A. chrysogenum. So far, CREA is the first transcription factor in A. chrysogenum which has been identified as being involved in regulatory processes in this fungus. The investigation of nutrient-dependent and strain-specific regulatory mechanisms may serve to optimize the industrial cultivation and the targeted strain improvement by genetic engendering.