Bioprocess for preparing 7-adca

Details Bioprocess for preparing 7-adca Bioprocess for preparing 7-adca

C - Chemistry, Metallurgy

12

N

C12N 15/52 (2006.01) C12N 1/15 (2006.01) C12N 9/02 (2006.01) C12N 15/55 (2006.01) C12N 15/80 (2006.01) C12P 17/18 (2006.01) C12P 35/00 (2006.01) C12P 37/04 (2006.01)

Patent

CA 2077921

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 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.

Un important intermédiaire pour la préparation d'antibiotiques de type céphalosporine, soit l'acide 7-aminodésacétoxycéphalosporanique, est préparé à l'aide d'un nouveau bioprocédé, dans lequel une souche transformée de Penicillium chrysogenum est cultivée en présence d'un stock d'adipate pour la production d'adipoyl-6-APA (acide 6-aminopénicillanique); l'expression in situ du gène de l'expandase, p. ex. à partir de Streptomyces clavuligerus, avec lequel la souche de P. chrysogenum a été transformée, convertit l'adipoyl-6-APA par une expansion de cycle en adipoyl-7-ADCA. Le produit final, 7-ADCA, est ensuite préparé par clivage de la chaîne latérale de l'adipoyle à l'aide d'une adipoyl-acylase. La synthèse totale est ainsi effectuée en utilisant les bioprocédés; elle est efficace et économique.

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