C - Chemistry – Metallurgy – 12 – P
Patent
C - Chemistry, Metallurgy
12
P
C12P 17/18 (2006.01) C12N 1/15 (2006.01) C12N 9/00 (2006.01) C12N 9/02 (2006.01) C12N 9/10 (2006.01) C12N 15/53 (2006.01) C12N 15/54 (2006.01) C12N 15/60 (2006.01) C12N 15/62 (2006.01) C12N 15/80 (2006.01) C12P 35/00 (2006.01) C12P 37/04 (2006.01)
Patent
CA 2080573
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 P. 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-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-aminodeacetylcephalosporanic acid (7-ADAC); and 3) an acetyltransferase gene whose expression product converts the 3-hydroxymethyl side chain to the 3-acetyloxymethyl side chain of 7-ACA. The final product, 7-ACA, 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.
Conder Michael J.
Crawford Lorilee
Mcada Phyllis C.
Rambosek John A.
Reeves Christopher D.
Conder Michael J.
Crawford Lorilee
Gist-Brocades B.v.
Mcada Phyllis C.
Ogilvy Renault Llp/s.e.n.c.r.l.,s.r.l.
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