Ampicillin Synthesis Using a Two-Enzyme Cascade with Both α-Amino Ester Hydrolase and Penicillin G Acylase

Authors

  • Janna K. Blum,

    1. School of Chemical and Biomolecular Engineering, Parker H. Petit Institute of Bioengineering and Bioscience, 315 Ferst Drive, Atlanta, GA 30332-0363 (USA)
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  • Andria L. Deaguero,

    1. School of Chemical and Biomolecular Engineering, Parker H. Petit Institute of Bioengineering and Bioscience, 315 Ferst Drive, Atlanta, GA 30332-0363 (USA)
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  • Carolina V. Perez,

    1. School of Chemical and Biomolecular Engineering, Parker H. Petit Institute of Bioengineering and Bioscience, 315 Ferst Drive, Atlanta, GA 30332-0363 (USA)
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  • Andreas S. Bommarius Prof.

    1. School of Chemical and Biomolecular Engineering, Parker H. Petit Institute of Bioengineering and Bioscience, 315 Ferst Drive, Atlanta, GA 30332-0363 (USA)
    2. School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta,GA 30332-0400 (USA), Fax: (+1) 404-894-2291
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Abstract

The current enzymatic production of semisynthetic β-lactam antibiotics requires isolation and purification of the intermediate 6-aminopenicillanic acid which adds cost and complexity to the manufacturing process. In this work, we took advantage of the unique substrate specificity of α-amino ester hydrolases to perform a purely aqueous one-pot production of ampicillin from penicillin G and D-phenylglycine methyl ester, catalyzed by α-amino ester hydrolase and penicillin G acylase. The synthesis was performed in both a one-pot, one-step synthesis resulting in a maximum conversion of 39 %, and a one-pot, two-step process resulting in a maximum conversion of 47 %. The two-enzyme cascade reported in this paper is a promising alternative to the current enzymatic two-step, two-pot manufacturing process for semisynthetic β-lactam antibiotics which requires intermittent isolation of 6-aminopenicillanic acid.

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