Direct Reductive Amination of Ketones: Structure and Activity of S-Selective Imine Reductases from Streptomyces

Authors

  • Tobias Huber,

    1. Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany)
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  • Lisa Schneider,

    1. Institute of Biochemistry, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg (Germany)
    2. BIOSS Centre for Biological Signalling Studies, Hebelstrasse 25, 79104 Freiburg (Germany)
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  • Dr. Andreas Präg,

    1. Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany)
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  • Dr. Stefan Gerhardt,

    1. Institute of Biochemistry, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg (Germany)
    2. BIOSS Centre for Biological Signalling Studies, Hebelstrasse 25, 79104 Freiburg (Germany)
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  • Prof. Dr. Oliver Einsle,

    1. Institute of Biochemistry, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg (Germany)
    2. BIOSS Centre for Biological Signalling Studies, Hebelstrasse 25, 79104 Freiburg (Germany)
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  • Prof. Dr. Michael Müller

    Corresponding author
    1. Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany)
    • Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany)

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Abstract

The importance and structural diversity of chiral amines is well-demonstrated by the myriad nonenzymatic methods for their chemical production. In nature, the production of amines is performed by transamination rather than by reduction of an imine precursor derived from the corresponding ketone. Imine reductases, however, show great potential in the reduction of cyclic imines that are stable towards hydrolysis in aqueous reaction media. Here, we report the catalytic activity of two S-selective imine reductases towards 3,4-dihydroisoquinolines and 3,4-dihydro-β-carbolines and their activity in the direct reductive amination of ketone substrates. The crystal structures of the enzyme from Streptomyces sp. GF3546 in complex with the cofactor NADPH and from Streptomyces aurantiacus in native form have been solved and refined to a resolution of 1.9 Å.

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