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Open Access An Industrial View on Enzymes for the Cleavage of Cephalosporin C

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The enzymatic cleavage of cephalosporin C (CephC) into 7-aminocephalosporanic acid (7-ACA) and deacetyl-7-aminocephalosporanic acid (HACA), both key intermediates for cephalosporin antibiotics, has now been commercialized on an industrial scale. This article illustrates economic, technical, and regulatory aspects of the process, with special focus on the enzymes involved.

Due to the compensation for low operational stability by low costs of preparation, cell immobilization of Trigonopsis variabilis seems an economically attractive and technically feasible way to prepare D-amino acid oxidase (EC 1.4.3.3). However, the application of immobilized cells is restricted to large-volume products, since it involves extensive development and characterization work.

For glutaryl-7-ACA acylase (EC 3.5.1.3), expressed in Escherichia coli, isolation and immobilization of the enzyme on a commercial carrier seems more attractive from a regulatory point of view. The immobilized enzyme shows very high operational stability, which may compensate for the costs of the carrier.

Despite its lower stability, cephalosporin G acetylesterase (EC 3.1.1.41), expressed in E. coli, was also immobilized on a commercial carrier for regulatory reasons. Moreover, extensive development of immobilized whole cells seemed economically not acceptable for this low-volume product.

A mathematical model for the enzymatic cleavage showed limitations of a combined application of two biocatalysts in a stirred tank reactor, e.g., in terms of product yield.
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Document Type: Research Article

Publication date: December 1, 1999

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  • International Journal for Chemistry and Official Membership Journal of the Swiss Chemical Society (SCS) and its Divisions

    CHIMIA, a scientific journal for chemistry in the broadest sense, is published 10 times a year and covers the interests of a wide and diverse readership. Contributions from all fields of chemistry and related areas are considered for publication in the form of Review Articles and Notes. A characteristic feature of CHIMIA are the thematic issues, each devoted to an area of great current significance.

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