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Biosynthetic Origin of the Antibiotic Cyclocarbamate Brabantamide A (SB‐253514) in Plant‐Associated Pseudomonas. |
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| Authors: | Dr. Yvonne Schmidt Dr. Menno van der Voort Dr. Max Crüsemann Prof. Dr. Jörn Piel Michaele Josten Prof. Dr. Hans‐Georg Sahl Henrike Miess Prof. Dr. Jos M. Raaijmakers Prof. Dr. Harald Gross |
| Affiliation: | 1. Institute for Pharmaceutical Biology, University of Bonn, Nussallee 6, 53115 Bonn (Germany);2. Laboratory of Phytopathology, Wageningen University, PO Box 8025, 6700 EE, Wageningen (The Netherlands);3. Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard‐Domagk‐Strasse 1, 53121 Bonn (Germany);4. currently at CMBB/Scripps Institution of Oceanography, UCSD, 9500 Gilman Drive, San Diego, CA 92093‐0204 (USA);5. Institute of Microbiology, Eidgen?ssische Technische Hochschule (ETH) Zürich, Vladimir‐Prelog‐Weg 1–5/10, 8093 Zürich (Switzerland);6. Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, Meckenheimer Allee 168, 53115 Bonn (Germany);7. German Centre for Infection Research (DZIF), partner site Bonn‐Cologne, Meckenheimer Allee 168, 53115 Bonn (Germany);8. Pharmaceutical Institute, Department of Pharmaceutical Biology, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen (Germany);9. Microbial Ecology Department, Netherlands Institute of Ecology (NIOO‐KNAW), Droevendaalsesteeg10, 6708 PB Wageningen (The Netherlands) |
| Abstract: | Within the framework of our genome‐based program to discover new antibiotic lipopeptides from Pseudomonads, brabantamides A–C were isolated from plant‐associated Pseudomonas sp. SH‐C52. Brabantamides A–C displayed moderate to high in vitro activities against Gram‐positive bacterial pathogens. Their shared structure is unique in that they contain a 5,5‐bicyclic carbamate scaffold. Here, the biosynthesis of brabantamide A (SB‐253514) was studied by a combination of bioinformatics, feeding experiments with isotopically labelled precursors and in vivo and in vitro functional analysis of enzymes encoded in the biosynthetic pathway. The studies resulted in the deduction of all biosynthetic building blocks of brabantamide A and revealed an unusual feature of this metabolite: its biosynthesis occurs via an initially formed linear di‐lipopeptide that is subsequently rearranged by a novel FAD‐dependent Baeyer–Villiger monooxygenase. |
| Keywords: | biosynthesis carbamates monooxygenases peptides Pseudomonas SB‐253514 |