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In situ product recovery (ISPR) by crystallization: basic principles, design, and potential applications in whole-cell biocatalysis


The removal of inhibiting or degrading product from a bioreactor as soon as the product is formed is an important issue in industrial bioprocess development. In this review, the potential of crystallization as an in situ product removal (ISPR) technique for the biocatalytic production of crystalline compounds is discussed. The emphasis of this review is on the current status of crystalline product formation by metabolically active cells for application in fine-chemicals production. Examples of relevant biocatalytic conversions are summarized, and some basic process options are discussed. Furthermore, a case study is presented in which two conceptual process designs are compared. In one process, product formation and crystallization are integrated by applying ISPR, whereas a second, nonintegrated process is based on a known conventional process equivalent for the production of 6R-dihydro-oxoisophorone. The comparison indicates that employing ISPR leads to significant advantages over the nonintegrated case in terms of increased productivity and yield with a corresponding decrease in the number of downstream processing steps, as well as in the quantity of waste streams. This leads to an economically more interesting process alternative. Finally, a general outlook on the various research aspects of ISPR by crystallization is given.

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This study has partly been funded by the Joint Financing Program for Cooperation in Higher Education–University of San Carlos–Delft University of Technology Project in Chemical Engineering. The following persons are gratefully acknowledged for their important contributions to this work: Sjoerd Blokker, Marcel Dabkowski, Willem Groendijk, Dirk Renckens, Jeroen de Rond, and Johan Grievink of the Delft University of Technology.

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Correspondence to Adrie J. J. Straathof.

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Buque-Taboada, E.M., Straathof, A.J.J., Heijnen, J.J. et al. In situ product recovery (ISPR) by crystallization: basic principles, design, and potential applications in whole-cell biocatalysis. Appl Microbiol Biotechnol 71, 1–12 (2006).

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