Bioprocess for preparing 7-ACA and 7-ADAC
US5559005A · kind A · utility
Assignee
Inventors
Key dates
| Filing date | May 27, 1994 |
| Grant date | Sep 24, 1996 |
| Priority date | — |
| Expiry date | May 27, 2014 |
Classification
- Technology area (CPC Y)Emerging Cross-Sectional Technologies
- CPC primaryY10S435/935
- WIPO fieldBiotechnology
- WIPO sectorChemistry
Abstract
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: PA1 1) an expandase gene, e.g., from Cephalosporium acremonium, whose expression product converts the adipoyl-6-APA by ring expansion to adipoyl-7-ADCA; PA1 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 PA1 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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.