Abstract
7-Aminodeacetoxycephalosporanic acid (7-ADCA) and 7-aminocephalosporanic acid (7-ACA) are the starting materials for the production of all clinically important semisynthetic derivatives of cephalosporins. Whereas 7-ADCA is conventionally produced from penicillin by a synthetic chemical method, here we describe an alternative bioprocess for its production. The method is based on the disruption by one-step replacement of the cefEF gene, encoding the bifunctional expandase/hydroxylase activity, of a cephalosporin C-producing strain of Acremonium chrysogenum. Subsequently, cloning and expression of the cefE gene from Streptomyces clavuligerus in the A. chrysogenum disrupted transformant yield recombinant strains producing deacetoxycephalosporin C (DAOC). DAOC production level is almost equivalent to the total β-lactams biosynthesized by the parental strain. DAOC deacylation is carried out by two final enzymatic bioconversions catalyzed by D-amino acid oxidase (DAO) and glutaryl acylase (GLA), yielding 7-ADCA.
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RodrÍguez-Sáiz, M., de la Fuente, JL., Barredo, JL. (2005). Metabolic Engineering of Acremonium chrysogenum to Produce Deacetoxycephalosporin C and Bioconversion to 7-Aminodeacetoxycephalosporanic Acid. In: Barredo, JL. (eds) Microbial Processes and Products. Methods in Biotechnology, vol 18. Humana Press. https://doi.org/10.1385/1-59259-847-1:041
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DOI: https://doi.org/10.1385/1-59259-847-1:041
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