Effect of temperature on the enzymatic synthesis of cefaclor with in situ product removal

An integrated process of cefaclor synthesis from phenylglycine methyl ester (PGME) and 7-aminodesacetoxymethyl-3-chlorocephalosporanic acid (7-ACCA) catalyzed by penicillin G acylase (PGA) with in situ product removal (ISPR) was established. The integrated process was more significantly influenced by temperature than the separate synthesis process as without ISPR. The difference between the overall yields with and without ISPR was minified as reaction temperatures rose. For instance, the maximum 7-ACCA conversion was 86 and 68%, respectively, in the process with and without ISPR at 5 °C. Both the maximum conversions, however, decreased to around 45% at 40 °C. The effect of substrate concentration on the overall conversion was also obviously dependent on the reaction temperature. The product cefaclor inhibited PGME hydrolysis in the enzymatic synthesis. ISPR stimulated cefaclor synthesis at lower temperatures, but was not useful at higher temperatures which accelerated PGME hydrolysis.