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Enhanced Enzymatic Synthesis of a Cephalosporin, Cefadroclor, in the Presence of Organic Co-solvents

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Abstract

In this study, we investigated the enzymatic synthesis of a semi-synthetic cephalosporin, cefadroclor, from 7-aminodesacetoxymethyl-3-chlorocephalosporanic acid (7-ACCA) and p-OH-phenylglycine methyl ester (D-HPGM) using immobilized penicillin G acylase (IPA) in organic co-solvents. Ethylene glycol (EG) was employed as a component of the reaction mixture to improve the yield of cefadroclor. EG was found to increase the yield of cefadroclor by 15–45%. An investigation of altered reaction parameters including type and concentration of organic solvents, pH of reaction media, reaction temperature, molar ratio of substrates, enzyme loading, and IPA recycling was carried out in the buffer mixture. The best result was a 76.5% conversion of 7-ACCA, which was obtained from the reaction containing 20% EG (v/v), D-HPGM to 7-ACCA molar ratio of 4:1 and pH 6.2, catalyzed by 16 IU mL−1 IPA at 20 °C for 10 h. Under the optimum conditions, no significant loss of IPA activity was found after seven repeated reaction cycles. In addition, cefadroclor exhibited strong inhibitory activity against yeast, Bacillus subtilis NX-2, and Escherichia coli and weaker activity against Staphylococcus aureus and Pseudomonas aeruginosa. Cefadroclor is a potential antibiotic with activity against common pathogenic microorganisms.

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Acknowledgements

This work was supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (11KJD180001), the Natural Science Foundation of Jiangsu Education Ministry (14KJB530005), and the Science and Technology Program of Joint Innovation Fund—A Prospective Joint Research Project in Jiangsu Province (No. BY2014005-10).

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Authors and Affiliations

  1. State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China

    Kun Liu, Sha Li, Xiao Pang, Zheng Xu & Hong Xu

  2. College of Food Science and Light Industry, Nanjing Tech University, No. 30 South of Puzhu Road, Pukou District, 211800, Nanjing, China

    Kun Liu, Sha Li, Xiao Pang, Zheng Xu & Hong Xu

  3. School of Life Science, Huaiyin Normal University, No. 111 West of Changjiang Road, Huaiyin District, 223300, Huai’an, China

    Dengchao Li

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  1. Kun Liu
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  2. Sha Li
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Correspondence to Dengchao Li or Hong Xu.

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Liu, K., Li, S., Pang, X. et al. Enhanced Enzymatic Synthesis of a Cephalosporin, Cefadroclor, in the Presence of Organic Co-solvents. Appl Biochem Biotechnol 182, 29–40 (2017). https://doi.org/10.1007/s12010-016-2308-0

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