| abstract |
An important intermediate for preparing cephalosporin antibiotics, 7-aminodesacetoxy cephalosporanic acid (7-ADCA), is prepared by a novel bioprocess in which a transformed $i(Penicillium chrysogenum) strain is cultured in the presence of an adipate feesdstock to produce adipoyl-6-APA (6-amino penicillanic acid); and the $i(in situ) expression of an expandase gene, e.g., from $i(Streptomyces clavuligerus), with which the $i(P. chrysogenum) has been transformed, converts the adipoyl-6-APA by ring expansion to adipoyl-7-ADCA. The final product, 7-ADCA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase. The entire synthesis, accordingly, is carried out using bioprocesses, and is efficient and economical. |