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Guidelines for development and implementation of biocatalytic P450 processes

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Abstract

Biocatalytic reactions performed by cytochrome P450 monooxygenases are interesting in pharmaceutical research since they are involved in human drug metabolism. Furthermore, they are potentially interesting as biocatalysts for synthetic chemistry because of the exquisite selectivity of the chemistry they undertake. For example, selective hydroxylation can be undertaken on a highly functionalized molecule without the need for functional group protection. Recent progress in the discovery of novel P450s as well as protein engineering of these enzymes strongly encourages further development of their application, including use in synthetic processes. The biological characteristics of P450s (e.g., cofactor dependence) motivate the use of whole-cell systems for synthetic processes, and those processes implemented in industry are so far dominated by growing cells and native host systems. However, for an economically feasible process, the expression of P450 systems in a heterologous host with sufficient biocatalyst yield (g/g cdw) for non-growing systems or space-time yield (g/L/h) for growing systems remains a major challenge. This review summarizes the opportunities to improve P450 whole-cell processes and strategies in order to apply and implement them in industrial processes, both from a biological and process perspective. Indeed, a combined approach of host selection and cell engineering, integrated with process engineering, is suggested as the most effective route to implementation.

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Acknowledgments

MTL has received funding from the People Programme (Marie Curie Actions) of the European Union’s 7th Framework Programme (FP7/2007-2013) under REA Grant Agreement 289217.

Conflict of interest

The authors declare that they have no conflict of interest.

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  1. Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, 2800, Kgs. Lyngby, Denmark

    Marie T. Lundemo & John M. Woodley

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  1. Marie T. Lundemo
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  2. John M. Woodley
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Correspondence to John M. Woodley.

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Lundemo, M.T., Woodley, J.M. Guidelines for development and implementation of biocatalytic P450 processes. Appl Microbiol Biotechnol 99, 2465–2483 (2015). https://doi.org/10.1007/s00253-015-6403-x

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  • DOI: https://doi.org/10.1007/s00253-015-6403-x

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