BIOLOGICAL PROCESS FOR PREPARING 7-AMINODEACETYLCEPHALOSPORANIC ACID, METHOD OF GROWING RECOMBINANT CELLS PENICILLIUM CHRYSOGENUM AND A VECTOR FOR EXPRESSION OF RECOMBINANT DNA

摘要

In the present invention there is disclosed a novel bioprocess for preparing 7-aminodeacetylcephalosporanic acid 7-ADAC. The process is characterized in that (1) a Penicillium chrysogenum strain producing isopenicillin N is cultured in a corresponding nutrient medium and in the nutrient medium there is then added an adipate feedstock, i.e. adipic acid salts or esters thereof that can be assimilated and employed by the Penicillium chrysogenum strain to produce adipoyl-6-APA (6-amino penicillanic acid); (2) followed by the in situ expression of the following genes with which the Penicillium chrysogenum has been transformed: 1) an expandase gene, e.g., from Cephalosporium acremonium, whose expression product converts the adipoyl-6-APA by ring expansion to adipoyl-7-aminodeacetylcephalosporanic acid, adipoyl-7-ADCA; 2) an hydroxylase gene whose expression product converts the 3-methyl side chain of adipoyl-7-ADCA to 3-hydroxymethyl, to give the first product, 7-aminodeacetylcephalosporani