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Antiterminator-Mediated Unveiling of Cryptic Polythioamides in an Anaerobic Bacterium

Authors

  • Dipl.-Biochem. Swantje Behnken,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Dept. of Biomolecular Chemistry, and Bio Pilot Plant, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Dr. Thorger Lincke,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Dept. of Biomolecular Chemistry, and Bio Pilot Plant, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Dipl.-Chem. Florian Kloss,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Dept. of Biomolecular Chemistry, and Bio Pilot Plant, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Dr. Keishi Ishida,

    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Dept. of Biomolecular Chemistry, and Bio Pilot Plant, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • Prof. Dr. Christian Hertweck

    Corresponding author
    1. Leibniz Institute for Natural Product Research and Infection Biology, HKI, Dept. of Biomolecular Chemistry, and Bio Pilot Plant, Beutenbergstrasse 11a, 07745 Jena (Germany)
    2. Friedrich Schiller University, Jena (Germany)
    • Leibniz Institute for Natural Product Research and Infection Biology, HKI, Dept. of Biomolecular Chemistry, and Bio Pilot Plant, Beutenbergstrasse 11a, 07745 Jena (Germany)
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  • We thank A. Perner for MS measurements and E. T. Papoutsakis for providing plasmid pSOS95. We are grateful to U. Knüpfer for support in 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 Microbial and Biomolecular Interactions (ILRS), as part of the excellence graduate school “Jena School for Microbial Communication” (JSMC).

Abstract

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Anti-Terminator: Rise of the Molecules: Overexpression of an antiterminator gene (nusG) in Clostridium cellulolyticum induced the biosynthesis of the novel antibiotic closthioamide and related thioamides. This is the first successful genetic engineering of an anaerobe to trigger a cryptic pathway. Furthermore, synthetic probes provide valuable insights into the biogenetic relationship of the rare thioamide metabolites.

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