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AssigneeMerck & Co., Inc.
InventorsMichael J. Conder, Phyllis C. McAda, John A. Rambosek
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An important intermediate for preparing cephalosporin antibiotics, 7-aminodesacetoxy cephalosporanic acid (7-ADCA), is 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); and the in situ expression of an expandase gene, e.g., from Streptomyces clavuligerus, with which the P. chrysogenum has been transformed, converts the adipoly-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.
A bioprocess for preparing 7-aminodesacetoxy cephalosporanic acid (7-ADCA) comprising the steps of
A method of producing adipoyl-7-ADCA in vivo comprising culturing a recombinant Penicillium chrysogenum host cell designated PC100, ATCC 74182 in the presence of adipic acid, or salts and esters thereof, wherein said host cell is expressing recombinant expandase enzyme.
An in vivo method for the in situ production of adipoyl-7-ADCA comprising the steps:
A method for the production of 7-ADCA comprising the steps:
Dependencies are inferred from the claim text.