Genome-Led Discovery of the Antibacterial Cyclic Lipopeptide Kutzneridine A and Its Silent Biosynthetic Gene Cluster from <i>Kutzneria</i> Species
Genome analysis of <i>Kutzneria</i> sp. CA-103260 revealed a putative lipopeptide-encoding biosynthetic gene cluster (BGC) that was cloned into a bacterial artificial chromosome (BAC) and heterologously expressed in <i>Streptomyces coelicolor</i> M1152. As a result, a novel cyclic lipo-tetrapeptide containing two diaminopropionic acid residues and an exotic <i>N</i>,<i>N</i>-acetonide ring, kutzneridine A (<b>1</b>), was isolated and structurally characterized. Evaluation of the extraction conditions and isotope-labeling chemical modifications showed that the acetonide ring originated from acetone during isolation. The BGC was analyzed <i>in silico</i> and a biosynthetic pathway to <b>1</b> was proposed. Kutzneridine A displayed remarkable antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant <i>Enterococci</i>.
Authors
- Daniel Oves‐Costales (ORCID: https://orcid.org/0000-0001-9986-4623)
- Fernando Reyes (ORCID: https://orcid.org/0000-0003-1607-5106)
- Jesús Martı́n (ORCID: https://orcid.org/0000-0001-7487-2790)
- Pilar Sánchez (ORCID: https://orcid.org/0000-0002-6034-1857)
- Kai Blin (ORCID: https://orcid.org/0000-0003-3764-6051)
- Ignacio Fernández-Pastor (ORCID: https://orcid.org/0000-0003-1729-0860)
- Olga Genilloud (ORCID: https://orcid.org/0000-0002-4202-1219)
- Tetiana Gren (ORCID: https://orcid.org/0000-0003-2517-9978)
- Jaime Felipe Guerrero Garzón (ORCID: https://orcid.org/0000-0002-1492-4816)
- José R. Tormo (ORCID: https://orcid.org/0000-0001-6984-2941)
- Tue Sparholt Jørgensen (ORCID: https://orcid.org/0000-0002-2437-7086)
- Mercedes de la Cruz (ORCID: https://orcid.org/0000-0002-2389-8576)
- Xinglin Jiang (ORCID: https://orcid.org/0000-0002-4935-8025)
- Tilmann Weber (ORCID: https://orcid.org/0000-0002-8260-5120)
- Eva Baggesgaard Sterndorff (ORCID: https://orcid.org/0009-0008-2920-9058)
- Francisco Javier Ortiz‐López (ORCID: https://orcid.org/0000-0002-9410-3718)
Institutions
- Novo Nordisk Foundation (DK)
- Fundación Medina (ES)
- Technical University of Denmark (DK)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2024-09-27
- DOI
- https://doi.org/10.1021/acs.jnatprod.4c00633
- Citations
- 4
- Primary Topic
- Microbial Natural Products and Biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 1.79
Funders
- Novo Nordisk Fonden