The Intricate Nonribosomal Assembly of a Potent Antifungal Lipopeptide from the <i>Burkholderia cepacia</i> Complex
The <i>Burkholderia cepacia</i> complex (BCC) is a group of Gram-negative bacteria known for their pathogenicity to patients suffering from cystic fibrosis (CF). The BCC-belonging strain <i>B. pyrrocinia</i> BC11 (formerly <i>B. cepacia</i> BC11) produces AFC-BC11, a compound with strong activity against phytopathogenic fungi. In this contribution, we report on the unprecedented <i>N</i>-acyl-tetrapeptide structure and antifungal potency of this natural product. We further provide insights into central steps of its biosynthesis mediated by a nonclassical nonribosomal peptide synthesis machinery lacking condensation domains. With the involvement of a sole acyl/peptidyl carrier protein AfcK, an acyltransferase AfcL and coenzyme A, the growing acyl-peptide chain is shuffled between different thioester carriers during the intricate biosynthetic assembly. The knowledge of the AFC-BC11 structure may contribute to the development of antifungals against phytopathogens and, with the <i>afc</i> gene cluster being conserved in various <i>Burkholderia</i> strains, possibly to an understanding of the human pathogenesis of the BCC.
Authors
- Manuel Gemander (ORCID: https://orcid.org/0000-0002-2112-6409)
- Tam Dang (ORCID: https://orcid.org/0000-0002-3602-1917)
- Roderich D. Süßmuth (ORCID: https://orcid.org/0000-0001-7027-2069)
- Andi Mainz (ORCID: https://orcid.org/0000-0003-3428-864X)
- Maria Seidel (ORCID: https://orcid.org/0000-0003-2838-8230)
- Lei Zhong (ORCID: https://orcid.org/0000-0003-4842-7145)
- Annette Poch
- Sebastian Kemper (ORCID: https://orcid.org/0000-0003-0192-518X)
- Stéphane Cociancich (ORCID: https://orcid.org/0000-0001-8601-3598)
- Agnes Mühlenweg
- Grit Walther (ORCID: https://orcid.org/0000-0003-0022-9027)
- Dan Xu (ORCID: https://orcid.org/0000-0003-1753-3594)
- Dou Hong (ORCID: https://orcid.org/0009-0000-6281-7532)
- Monique Royer
- Sarah Yammine
- Malo Boulanger
- Franziska Graeger
- Yasemin Kirimlioglu
- Lisa Großgloß
Institutions
- Centre de Coopération Internationale en Recherche Agronomique pour le Développement (FR)
- Université de Montpellier (FR)
- Institut Agro Montpellier (FR)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Institut Agro Montpelier (FR)
- Services déconcentrés d'appui à la recherche Occitanie-Montpellier (FR)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Institut de Recherche pour le Développement (FR)
- Plant Health Institute de Montpellier (FR)
- L'Institut Agro (FR)
- Technische Universität Berlin (DE)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2025-06-02
- DOI
- https://doi.org/10.1021/jacs.5c04167
- Citations
- 2
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 2.79
Funders
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- China Scholarship Council