BIOPROCESSES FOR PREPARING 7-AMINO-CEPHALOSPORANIC ACID AND 7-AMINODEACETYLCEPHALOSPORANIC ACID, RECOMBINANT DNA EXPRESSION VECTORS, RECOMBINANT PRODUCTION STRAINS OF PENICILLIUM CHRYSOGENUM USABLE IN THE PROCESS, AND THE USE OF RECOMBINANT PRODUCTION STRAINS

摘要

Important intermediates for preparing cephalosporin antibiotics, 7-amino-cephalosporanic acid (7-ACA) and 7-aminodeacetylcephalosporanic acid (7-ADAC), are prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); followed by the in situ expression of the following genes with which the Penicillium chrysogenum has been transformed: 1) an expandase gene gives adipoyl-7-ADCA; 2) a hydroxylase gene gives (7-ADAC); and 3) an acetyltransferase gene gives adipoyl-7-ACA. The final product, 7-ACA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase. The invention also provides recombinant DNA expression vectors and recombinant production strains of Penicillium chrysogenum and the use thereof.