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Mechanism-Inspired Engineering of Phenylalanine Aminomutase for Enhanced β-Regioselective Asymmetric Amination of Cinnamates

Authors

  • Dr. Bian Wu,

    1. Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen (The Netherlands)
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  • Dr. Wiktor Szymański,

    1. Center for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen (The Netherlands)
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  • Gjalt G. Wybenga,

    1. Laboratory of Biophysical Chemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen (The Netherlands)
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  • Matthew M. Heberling,

    1. Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen (The Netherlands)
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  • Dr. Sebastian Bartsch,

    1. Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen (The Netherlands)
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  • Dr. Stefaan de Wildeman,

    1. DSM Pharmaceutical Products, Geleen (The Netherlands)
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  • Dr. Gerrit J. Poelarends,

    1. Department of Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen (The Netherlands)
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  • Prof. Ben L. Feringa,

    1. Center for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen (The Netherlands)
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  • Prof. Bauke W. Dijkstra,

    1. Laboratory of Biophysical Chemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen (The Netherlands)
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  • Prof. Dick B. Janssen

    Corresponding author
    1. Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen (The Netherlands)
    • Department of Biochemistry, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen (The Netherlands)
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  • The work was supported through B-Basic, a public–private NWO–ACTS program. The authors thank Dr. O. May and Dr. B. Kaptein from DSM and Hans Raj from the Department of Pharmaceutical Biology, University of Groningen, for helpful discussions.

Abstract

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Turn to switch: A mutant of phenylalanine aminomutase was engineered that can catalyze the regioselective amination of cinnamate derivatives (see scheme, red) to, for example, β-amino acids. This regioselectivity, along with the X-ray crystal structures, suggests two distinct carboxylate binding modes differentiated by Cβ[BOND]Cipso bond rotation, which determines if β- (see scheme) or α-addition takes place.

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