Engineering deacetoxycephalosporin C synthase as a catalyst for the bioconversion of penicillins.

Abstract

7-aminodeacetoxycephalosporanic acid (7-ADCA) is a key intermediate of many clinically useful semisynthetic cephalosporins that were traditionally prepared by processes involving chemical ring expansion of penicillin G. Bioconversion of penicillins to cephalosporins using deacetoxycephalosporin C synthase (DAOCS) is an alternative and environmentally friendly process for 7-ADCA production. Arnold Demain and co-workers pioneered such a process. Later, protein engineering efforts to improve the substrate specificity and catalytic efficiency of DAOCS for penicillins have been made by many groups, and a whole cell process using Escherichia coli for bioconversion of penicillins has been developed.