Recombinant expandase bioprocess for preparing 7-aminodesacetoxy

Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound having a 1-thia-5-aza-bicyclo

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435 51, 435183, 435230, 435935, C12P 3502, C12P 3506, C12N 984

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active

053188969

ABSTRACT:
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.

REFERENCES:
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patent: 5108918 (1992-04-01), Groenen et al.
Baldwin et al., "The Enzymatic Ring Expansion of Penicillins to Cephalosporins: Side Chain Specificity", Tetrahedron, 43:3009-3014, (1987).
Ballio et al., "Incorporation of .alpha.,.omega.-Dicarboxylic Acids as Side-chains into the Penicillin Molecule", Nature, 185:97-99 (1960).
Cantwell et al., "Cloning and Expression of a hybrid S. clavuligerus cefE gene . . . ", Curr. Genet., 17:213-221 (1990).
Matsuda et al., "Cloning and Characterization of the Genes . . . ", J. Bacteriol., 169:5815-5820 (1987).

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