Structure Elucidation, Total Synthesis, Antibacterial In Vivo Efficacy and Biosynthesis Proposal of Myxobacterial Corramycin.


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
19 12 2022
Historique:
received: 21 07 2022
pubmed: 6 10 2022
medline: 15 12 2022
entrez: 5 10 2022
Statut: ppublish

Résumé

Herein, we describe the myxobacterial natural product Corramycin isolated from Corallococcus coralloides. The linear peptide structure contains an unprecedented (2R,3S)-γ-N-methyl-β-hydroxy-histidine moiety. Corramycin exhibits anti-Gram-negative activity against Escherichia coli (E. coli) and is taken up via two transporter systems, SbmA and YejABEF. Furthermore, the Corramycin biosynthetic gene cluster (BGC) was identified and a biosynthesis model was proposed involving a 12-modular non-ribosomal peptide synthetase/polyketide synthase. Bioinformatic analysis of the BGC combined with the development of a total synthesis route allowed for the elucidation of the molecule's absolute configuration. Importantly, intravenous administration of 20 mg kg

Identifiants

pubmed: 36197755
doi: 10.1002/anie.202210747
pmc: PMC10099666
doi:

Substances chimiques

Anti-Bacterial Agents 0
Polyketide Synthases 79956-01-7

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202210747

Informations de copyright

© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Auteurs

Cédric Couturier (C)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Sebastian Groß (S)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Alexander von Tesmar (A)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Judith Hoffmann (J)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Selina Deckarm (S)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Anouchka Fievet (A)

Evotec, 40 avenue Tony Garnier, 69007, Lyon, France.

Nelly Dubarry (N)

Evotec, 40 avenue Tony Garnier, 69007, Lyon, France.

Thomas Taillier (T)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Christoph Pöverlein (C)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Heike Stump (H)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Michael Kurz (M)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Luigi Toti (L)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Sabine Haag Richter (S)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Dietmar Schummer (D)

Technische Hochschule Mittelhessen, Wiesenstraße 14, 35390, Gießen, Germany.

Philippe Sizun (P)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Michael Hoffmann (M)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Ram Prasad Awal (R)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Nestor Zaburannyi (N)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Kirsten Harmrolfs (K)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Joachim Wink (J)

Mikrobielle Stammsammlung, Helmholtz Centre for Infection Research (HZI), Inhoffenstraße 7, 38124, Braunschweig, Germany.

Emilie Lessoud (E)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Thierry Vermat (T)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Veronique Cazals (V)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Sandra Silve (S)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Armin Bauer (A)

Sanofi, 13, Quai Jules Guesde, 94400, Vitry-sur-Seine, France.

Michael Mourez (M)

Ecole d'Ingénieurs de Purpan, 75 voie du Toec, BP57611, 31076, Toulouse, France.

Laurent Fraisse (L)

Drug for Neglected Diseases Initiative, Chemin Camille-Vidart 15, 1202, Geneva, Switzerland.

Corinne Leroi-Geissler (C)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Astrid Rey (A)

Charles River Laboratories, 327 impasse du domaine rozier, 69210, Saint-Germain-Nuelles, France.

Stéphanie Versluys (S)

Evotec, 195, route d'Espagne, 31000, Toulouse, France.

Eric Bacqué (E)

Evotec, 1541, avenue Marcel Mérieux, 69280, Marcy L'Etoile, France.

Rolf Müller (R)

Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Department of Pharmacy at Saarland University, Campus Building E8.1, 66123, Saarbrücken, Germany.

Stephane Renard (S)

Evotec, 40 avenue Tony Garnier, 69007, Lyon, France.

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Classifications MeSH