Biosynthetic Origin of the Antibiotic Pseudopyronines A and B in Pseudomonas putida BW11M1
Judith S. Bauer
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
These authors contributed equally to this work.
Search for more papers by this authorDr. Maarten G. K. Ghequire
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, 3001 Heverlee-Leuven, Belgium
These authors contributed equally to this work.
Search for more papers by this authorDr. habil. Markus Nett
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
Search for more papers by this authorMichaele 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
Search for more papers by this authorProf. Dr. Hans-Georg Sahl
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
Search for more papers by this authorCorresponding Author
Prof. Dr. René De Mot
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, 3001 Heverlee-Leuven, Belgium
Search for more papers by this authorCorresponding Author
Prof. Dr. Harald Gross
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
Search for more papers by this authorJudith S. Bauer
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
These authors contributed equally to this work.
Search for more papers by this authorDr. Maarten G. K. Ghequire
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, 3001 Heverlee-Leuven, Belgium
These authors contributed equally to this work.
Search for more papers by this authorDr. habil. Markus Nett
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
Search for more papers by this authorMichaele 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
Search for more papers by this authorProf. Dr. Hans-Georg Sahl
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
Search for more papers by this authorCorresponding Author
Prof. Dr. René De Mot
Centre of Microbial and Plant Genetics, Department of Microbial and Molecular Systems, University of Leuven, Kasteelpark Arenberg 20, 3001 Heverlee-Leuven, Belgium
Search for more papers by this authorCorresponding Author
Prof. Dr. Harald Gross
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
Search for more papers by this authorGraphical Abstract
Only one enzyme does the job. Dialkylpyrones are commonly biosynthesized by polyketidic systems. However, in the case of the dialkylpyrones pseudopyronines A and B, mutagenic experiments correlated their biosynthesis to a single ppyS-like gene. Isotopic labelling experiments support a two-chain mechanism in which two fatty acids are fused by PpyS to give the secondary metabolite pseudopyronine.
Abstract
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.
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