Loss of glucose repression in an Acremonium chrysogenum β-lactam producer strain and its restoration by multiple copies of the cre1 gene

In the filamentous fungus Acremonium chrysogenum, biosynthesis of the beta -lactam antibiotic cepha losporin C is repressed by glucose. A wild-type strain grown in the presence of glucose shows a reduction of transcripts derived from the pcbC and cefEF biosynthesis genes. Interestingly, the amount of the pcbC transcript is not affected in another strain with enhanced cephalosporin C production, suggesting a correlation between strain improvement and deregulation of glucose repression. The function of the glucose repressor CRE1 in this regulation was further analyzed by transforming both A. chrysogenum strains with multiple copies of the cre1 gene. The molecular analysis of transformants revealed that additional copies of the cre1 gene restore wild-type-like regulation of pcbC gene expression in the semi-producer strain, while repression of the cefEF gene expression is increased. Overall, our data indicate a regulation of the pcbC and the cefEF gene expression by CRE1.