Salamandamide Lipodipeptides Are Biosynthetic Intermediate Shunt Products of the Nonamodular Nonribosomal Peptide Assembly Lines of the Viscosin Family
Chemical investigation of a salamander-mucus-associated <i>Pseudomonas tolaasii</i> strain led to the isolation and chemical characterization of salamandamide A, a new lipo-dipeptide, along with known lipopeptides of the pseudodesmin and tolaasin class. Genome mining revealed that no specific gene cluster codes for the biosynthesis of salamandamide A. Stereochemical analyses and mutagenesis experiments linked the biosynthesis of the lipo-dipeptide salamandamide A to the NRPS gene cluster of the lipo-nonapeptide pseudodesmin. Further chemical investigations showed that this finding appears to be a broader concept and that all nonamodular NRPS gene clusters of the viscosin family were capable to produce, beside the expected lipo-nonapeptide, the corresponding lipo-dipeptide as a shunt product which also led to the discovery of salamandamide B from <i>Pseudomonas lactis</i> SS101.
Authors
- Monica Höfte (ORCID: https://orcid.org/0000-0002-0850-3249)
- Natalia Ruétalo (ORCID: https://orcid.org/0000-0001-6798-0443)
- Michael Lämmerhofer (ORCID: https://orcid.org/0000-0002-1318-0974)
- Harald Gross (ORCID: https://orcid.org/0000-0002-0731-821X)
- Michael Schindler (ORCID: https://orcid.org/0000-0001-8989-5813)
- Rabea Voget (ORCID: https://orcid.org/0009-0003-9249-8773)
- Rosanna C. Hennessy (ORCID: https://orcid.org/0000-0002-2359-8565)
- Michael Gütschow (ORCID: https://orcid.org/0000-0002-9376-7897)
- Feyisara Eyiwumi Oni (ORCID: https://orcid.org/0000-0002-7013-9644)
- Jan Straetener
- Heike Brötz‐Oesterhelt (ORCID: https://orcid.org/0000-0001-9364-1832)
- Carly R. Muletz‐Wolz (ORCID: https://orcid.org/0000-0001-5047-9601)
- Thomas Majer
- Benedikt Masberg (ORCID: https://orcid.org/0000-0003-2041-4983)
- Keshab Bhattarai (ORCID: https://orcid.org/0000-0003-0824-0415)
- Ryan Karongo (ORCID: https://orcid.org/0000-0002-5481-3563)
- Dieter Schollmeyer
- Markus Krämer (ORCID: https://orcid.org/0009-0009-6298-3296)
- Tatjana Wannenwetsch
- Manuela Haussmann
Institutions
- University of Copenhagen (DK)
- University of Bonn (DE)
- Johannes Gutenberg University Mainz (DE)
- Smithsonian Conservation Biology Institute (US)
- Ghent University Hospital (BE)
- Rijk Zwaan (Netherlands) (NL)
- National Zoological Park (US)
- German Center for Infection Research (DE)
- Czech Academy of Sciences, Institute of Microbiology (CZ)
- University Children's Hospital Tübingen (DE)
- Genomics (United Kingdom) (GB)
- Institute of Virology of the Slovak Academy of Sciences (SK)
- Chemical Pharmaceutical Research Institute (BG)
- Conservation Biology Institute
- University of Tübingen (DE)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-04-15
- DOI
- https://doi.org/10.1021/acs.jnatprod.5c00084
- Primary Topic
- Biochemical and Structural Characterization
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Deutsches Zentrum für Infektionsforschung
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Directorate for Biological Sciences