Enzyme-Primed Native Chemical Ligation Produces Autoinducing Cyclopeptides in Clostridia.

Autor: Molloy EM; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Dell M; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Hänsch VG; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Dunbar KL; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Feldmann R; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Oberheide A; Institute for Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena, Humboldtstr. 10, 07743, Jena, Germany., Seyfarth L; Institute for Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena, Humboldtstr. 10, 07743, Jena, Germany., Kumpfmüller J; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Horch T; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany., Arndt HD; Institute for Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena, Humboldtstr. 10, 07743, Jena, Germany., Hertweck C; Dept. of Biomolecular Chemistry, Leibniz Institute for Natural, Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745, Jena, Germany.; Faculty of Biological Sciences, Friedrich Schiller University Jena, 07743, Jena, Germany.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2021 May 03; Vol. 60 (19), pp. 10670-10679. Date of Electronic Publication: 2021 Mar 26.
DOI: 10.1002/anie.202016378
Abstrakt: Clostridia coordinate many important processes such as toxin production, infection, and survival by density-dependent communication (quorum sensing) using autoinducing peptides (AIPs). Although clostridial AIPs have been proposed to be (thio)lactone-containing peptides, their true structures remain elusive. Here, we report the genome-guided discovery of an AIP that controls endospore formation in Ruminiclostridium cellulolyticum. Through a combination of chemical synthesis and chemical complementation assays with a mutant strain, we reveal that the genuine chemical mediator is a homodetic cyclopeptide (cAIP). Kinetic analyses indicate that the mature cAIP is produced via a cryptic thiolactone intermediate that undergoes a rapid S→N acyl shift, in a manner similar to intramolecular native chemical ligation (NCL). Finally, by implementing a chemical probe in a targeted screen, we show that this novel enzyme-primed, intramolecular NCL is a widespread feature of clostridial AIP biosynthesis.
(© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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