They include the penicillins and many of the cephalosporins.
DANS is an institute of KNAW and NWO
Expression of the cephalosporin biosynthesis genes in A. chrysogenum is controlled by several global regulators including the carbon catabolite repressor CreA (), the pH regulator PacC () and the winged helix transcriptional factor CPCR1 ().
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Taken together, these data show that in a wild-type strain of A. nidulans, expression of biosynthesis genes, at least of the acvA gene, is rate limiting. It remains to be elucidated, however, whether this holds for penicillin and cephalosporin production strains. Nevertheless, the expression level of biosynthesis genes, as shown for the cephalosporin C production, is of great importance.
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Skatrud et al. () reported a 15% increase in cephalosporin C production in an industrial strain of A. chrysogenum (394-4) by transformation of the strain with an extra copy of the DAOC synthetase/DAC hydroxylase gene (cefEF) (to give strain LU4-97-6) (Fig. ). However, when the experiments were carried out, it was not known that cefG encoding acetyl-CoA:DAC acetyltransferase is closely linked to cefEF (Fig. ) and was also present on the plasmid used for transformation. Then it was demonstrated that transformants of wild-type A. chrysogenum, carrying additional copies of the cefG gene only, showed a direct relationship between cefG copy number, cefG mRNA levels, and cephalosporin C titers, suggesting that this enzyme might be a rate-limiting step in cephalosporin C production (, ). Hence, the effect of the cefEF gene alone in increasing cephalosporin C production remains unclear.