Equilibrium position, kinetics, and reactor concepts for the adipyl-7-ADCA-hydrolysis process

C.G.P.H. Schroën, S. van de Wiel, P.J. Kroon, E. de Vroom, A.E.M. Janssen, J. Tramper

    Research output: Contribution to journalArticleAcademicpeer-review

    19 Citations (Scopus)

    Abstract

    One of the building blocks of cephalosporin antibiotics is 7-amino-deacetoxycephalosporanic acid (7-ADCA). It is currently produced from penicillin G using an elaborate chemical ring-expansion step followed by an enzyme-catalyzed hydrolysis. However, 7-ADCA-like components can also be produced by direct fermentation. This is of scientific and economic interest because the elaborate ring-expansion step is performed within the microorganism. In this article, the hydrolysis of the fermentation product adipyl-7-ADCA is studied. Adipyl-7-ADCA can be hydrolyzed in an equilibrium reaction to adipic acid and 7-ADCA using glutaryl-acylase. The equilibrium reaction yield is described as a function of pH, temperature, and initial adipyl-7-ADCA concentration. Reaction rate equations were derived for adipyl-7-ADCA-hydrolysis using three (pH-independent) reaction rate constants and the apparent equilibrium constant. The reaction rate constants were calculated from experimental data. Based on the equilibrium position and reaction rate equations the hydrolysis reaction was optimized and standard reactor configurations were evaluated. It was found that equilibrium yields are high at high pH, high temperature and low-initial adipyl-7-ADCA concentration. The course of the reaction could be described well as a function of pH (7-9), temperature (20-40°C) and concentration using the reaction rate equations. It was shown that a series of CSTR's is the best alternative for the process.
    Original languageEnglish
    Pages (from-to)654-661
    JournalBiotechnology and Bioengineering
    Volume70
    DOIs
    Publication statusPublished - 2000

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