Biosynthetic Origin of the Antibiotic Pseudopyronines A and B in Pseudomonas putida BW11M1.
Within the framework of our effort to discover new antibiotics from pseudomonads, pseudopyronines A and B were isolated from the plant-derived Pseudomonas putida BW11M1. Pseudopyronines are 3,6-dialkyl-4-hydroxy-2-pyrones and displayed high in vitro activities against several human pathogens, and in our hands also towards the plant pathogen Pseudomonas savastanoi. Here, the biosynthesis of pseudopyronine B was studied by a combination of feeding experiments with isotopically labeled precursors, genomic sequence analysis, and gene deletion experiments. The studies resulted in the deduction of all acetate units and revealed that the biosynthesis of these α-pyrones occurs with a single PpyS-homologous ketosynthase. It fuses, with some substrate flexibility, a 3-oxo-fatty acid and a further unbranched saturated fatty acid, both of medium chain-length and provided by primary metabolism.
Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.|German Centre for Infection Research (DZIF), Partner site Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany.
Judith S
JS
Bauer
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, 3001, Heverlee-Leuven, Belgium.
Maarten G K
MG
Ghequire
Junior Research Group "Secondary Metabolism of Predatory Bacteria", Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institut, Beutenbergstrasse 11 A, 07745, Jena, Germany.
Markus
M
Nett
Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, Meckenheimer Allee 168, 53115, Bonn, Germany.|German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Meckenheimer Allee 168, 53115, Bonn, Germany.
Michaele
M
Josten
Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), Pharmaceutical Microbiology Unit, University of Bonn, Meckenheimer Allee 168, 53115, Bonn, Germany.|German Centre for Infection Research (DZIF), Partner site Bonn-Cologne, Meckenheimer Allee 168, 53115, Bonn, Germany.
Hans-Georg
HG
Sahl
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, 3001, Heverlee-Leuven, Belgium. rene.demot@biw.kuleuven.be.
René
R
De Mot
Department of Pharmaceutical Biology, Pharmaceutical Institute, University of Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany. harald.gross@uni-tuebingen.de.|German Centre for Infection Research (DZIF), Partner site Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany. harald.gross@uni-tuebingen.de.
Harald
H
Gross
D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism; D002247:Carbon Isotopes / Q000737:chemistry; D005658:Fungi / Q000187:drug effects; D005798:Genes, Bacterial; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D005810:Multigene Family; D016296:Mutagenesis; D010088:Oxidoreductases / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D016958:Pseudomonas putida / Q000235:genetics / Q000378:metabolism*; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002247:Carbon Isotopes; D011753:Pyrones; C502674:pseudopyronine A; C502676:pseudopyronine B; D010088:Oxidoreductases
PpyS; Pseudomonas; alpha-pyrone; biosynthesis; natural products; sch 419560