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Epidithiol Formation by an Unprecedented Twin Carbon–Sulfur Lyase in the Gliotoxin Pathway

Authors

  • Daniel H. Scharf,

    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
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    • These authors contributed equally to this work.

  • Pranatchareeya Chankhamjon,

    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
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    • These authors contributed equally to this work.

  • Dr. Kirstin Scherlach,

    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Dr. Thorsten Heinekamp,

    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Dr. Martin Roth,

    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Prof. Dr. Axel A. Brakhage,

    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
    2. Friedrich Schiller University, Jena (Germany)
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  • Prof. Dr. Christian Hertweck

    Corresponding author
    1. Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
    2. Friedrich Schiller University, Jena (Germany)
    • Depts. of Biomolecular Chemistry, Molecular and Applied Microbiology, and Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • We thank A. Perner for MS measurements, S. Fricke and C. Schult for technical assistance, P. Hortschansky for artwork, and C. Heiden and P. Berthel for performing fermentations. This work was supported by the “Pakt für Forschung und Innovation” of the Free State of Thuringia and the BMBF, and the International Leibniz Research School for Biomolecular and Microbial Interactions (ILRS), as part of the excellence graduate school Jena School for Microbial Communication (JSMC).

Abstract

original image

Zwei auf einmal: Die Aufklärung des Schlüsselschritts in der Biosynthese von Gliotoxin, dem berüchtigten Virulenzfaktor des Humanpathogens Aspergillus fumigatus, gibt Einblicke in die Bildung eines Epidithiols. Die Isolierung eines Bis(cystein)-S-Konjugats aus einer ΔgliI-Mutante und In-vitro-Studien belegen, dass GliI zwei C-S-Bindungen auf einmal spaltet, wodurch Ammoniak und Pyruvat freigesetzt werden.

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