Effect of Substrate Concentration on the Synthesis of Cefaclor by Penicillin Acylase with in Situ Product Removal

Y. Zhang, D. Li, Q. Song, S. Liu and D. Z. Wei

Abstract
Enzymatic synthesis of 3-chloro-7-D-(2-phenylglycinamide)-3-cephem-4-carboxylic acid (cefaclor) by penicillin acylase (PA) was carried out with in situ product removal (ISPR) under kinetic control. The yield of cefaclor highly depended on substrate concentrations and the ratio of nucleus to acyl donor. Substrate concentrations were optimized as 50 mmol l–1 of 7-aminodesacetoxymethyl-3-chlorocephalosporanic acid (7ACCA) and 100 mmol l–1 of phenylglycine methyl ester (PGME) at the conditions: temperature 20 °C, pH 6.3; and enzyme load was 8 IU ml–1. It is effective to improve the transfer of acyl donor through controlling the substrate concentration with feeding acyl donor. The conversion of nucleus and acyl donor was improved to 93 % and 62 %, respectively.

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Keywords
Acyl donor feeding, 3-chloro-7-D-(2-phenylglycinamide)-3-cephem-4-carboxylic acid, enzymatic synthesis, in situ product removal, penicillin acylase, substrate concentration