title: Indexing the Pseudomonas specialized metabolome enabled the discovery of poaeamide B and the bananamides.
abstract: Pseudomonads are cosmopolitan microorganisms able to produce a wide array of specialized metabolites. These molecules allow Pseudomonas to scavenge nutrients, sense population density and enhance or inhibit growth of competing microorganisms. However, these valuable metabolites are typically characterized one-molecule-one-microbe at a time, instead of being inventoried in large numbers. To index and map the diversity of molecules detected from these organisms, 260 strains of ecologically diverse origins were subjected to mass-spectrometry-based molecular networking. Molecular networking not only enables dereplication of molecules, but also sheds light on their structural relationships. Moreover, it accelerates the discovery of new molecules. Here, by indexing the Pseudomonas specialized metabolome, we report the molecular-networking-based discovery of four molecules and their evolutionary relationships: a poaeamide analogue and a molecular subfamily of cyclic lipopeptides, bananamides 1, 2 and 3. Analysis of their biosynthetic gene cluster shows that it constitutes a distinct evolutionary branch of the Pseudomonas cyclic lipopeptides. Through analysis of an additional 370 extracts of wheat-associated Pseudomonas, we demonstrate how the detailed knowledge from our reference index can be efficiently propagated to annotate complex metabolomic data from other studies, akin to the way in which newly generated genomic information can be compared to data from public databases.
authors: Department of Chemistry and Biochemistry, University of California San Diego, California 92093, USA.
authors: Don D
authors: DD
authors: Nguyen
authors: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.
authors: Alexey V
authors: AV
authors: Melnik
authors: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.|Graduate School of Pharmaceutical Sciences, Kitasato University, Tokyo 108-8641, Japan.
authors: Nobuhiro
authors: N
authors: Koyama
authors: Bioinformatics Group, Wageningen University, Droevendaalsesteeg 1, 6708PB Wageningen, The Netherlands.
authors: Xiaowen
authors: X
authors: Lu
authors: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, California 92093, USA.
authors: Michelle
authors: M
authors: Schorn
authors: Department of Chemistry and Biochemistry, University of California San Diego, California 92093, USA.
authors: Jinshu
authors: J
authors: Fang
authors: Ion Torrent by Thermo Fisher, 5781 Van Allen Way, Carlsbad, California 92008, USA.
authors: Kristen
authors: K
authors: Aguinaldo
authors: Ion Torrent by Thermo Fisher, 5781 Van Allen Way, Carlsbad, California 92008, USA.
authors: Tommie L
authors: TL
authors: Lincecum
authors: Centre of Microbial and Plant Genetics, KU Leuven, 3001 Heverlee, Belgium.
authors: Maarten G K
authors: MG
authors: Ghequire
authors: Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), 6708PB Wageningen, The Netherlands.
authors: Victor J
authors: VJ
authors: Carrion
authors: Department of Ecology and Evolutionary Biology, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
authors: Tina L
authors: TL
authors: Cheng
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.
authors: Brendan M
authors: 0000-0002-7034-8374
authors: BM
authors: Duggan
authors: Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.|School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
authors: Jacob G
authors: JG
authors: Malone
authors: Department of AgroEcology, Rothamsted Research, West Common, Harpenden AL5 2JQ, UK.
authors: Tim H
authors: TH
authors: Mauchline
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.
authors: Laura M
authors: 0000-0001-9223-7977
authors: LM
authors: Sanchez
authors: Department of Ecology and Evolutionary Biology, University of California, 1156 High Street, Santa Cruz, California 95064, USA.
authors: A Marm
authors: AM
authors: Kilpatrick
authors: Department of Microbial Ecology, Netherlands Institute of Ecology (NIOO-KNAW), 6708PB Wageningen, The Netherlands.
authors: Jos M
authors: JM
authors: Raaijmakers
authors: Centre of Microbial and Plant Genetics, KU Leuven, 3001 Heverlee, Belgium.
authors: René
authors: R
authors: De Mot
authors: Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, California 92093, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.
authors: Bradley S
authors: BS
authors: Moore
authors: Bioinformatics Group, Wageningen University, Droevendaalsesteeg 1, 6708PB Wageningen, The Netherlands.
authors: Marnix H
authors: MH
authors: Medema
authors: Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.|Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, California 92093, USA.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, California 92093, USA.
authors: Pieter C
authors: PC
authors: Dorrestein
mesh_terms: D053898:Biosynthetic Pathways; D055666:Lipopeptides / Q000302:isolation & purification*; D013058:Mass Spectrometry; D055442:Metabolome; D010456:Peptides, Cyclic / Q000302:isolation & purification*; D011549:Pseudomonas / Q000737:chemistry* / Q000235:genetics; D014908:Triticum / Q000382:microbiology
chemical_list: D055666:Lipopeptides; D010456:Peptides, Cyclic