title: MS/MS-based networking and peptidogenomics guided genome mining revealed the stenothricin gene cluster in Streptomyces roseosporus.
abstract: Most (75%) of the anti-infectives that save countless lives and enormously improve quality of life originate from microbes found in nature. Herein, we described a global visualization of the detectable molecules produced from a single microorganism, which we define as the 'molecular network' of that organism, followed by studies to characterize the cellular effects of antibacterial molecules. We demonstrate that Streptomyces roseosporus produces at least four non-ribosomal peptide synthetase-derived molecular families and their gene subnetworks (daptomycin, arylomycin, napsamycin and stenothricin) were identified with different modes of action. A number of previously unreported analogs involving truncation, glycosylation, hydrolysis and biosynthetic intermediates and/or shunt products were also captured and visualized by creation of a map through MS/MS networking. The diversity of antibacterial compounds produced by S. roseosporus highlights the importance of developing new approaches to characterize the molecular capacity of an organism in a more global manner. This allows one to more deeply interrogate the biosynthetic capacities of microorganisms with the goal to streamline the discovery pipeline for biotechnological applications in agriculture and medicine. This is a contribution to a special issue to honor Chris Walsh's amazing career.
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Liu
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Lamsa
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA, USA.
authors.forename: Weng Ruh
authors.initials: WR
authors.lastname: Wong
authors.affiliation: Center for Marine Biotechnology and Biomedicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Boudreau
authors.affiliation: Center for Marine Biotechnology and Biomedicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Roland
authors.initials: R
authors.lastname: Kersten
authors.affiliation: Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Wilna J
authors.initials: WJ
authors.lastname: Moree
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Duggan
authors.affiliation: Center for Marine Biotechnology and Biomedicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
authors.affiliation: Center for Marine Biotechnology and Biomedicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
authors.affiliation: Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, CA, USA.
authors.forename: Roger G
authors.initials: RG
authors.lastname: Linington
authors.affiliation: Division of Biological Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Kit
authors.initials: K
authors.lastname: Pogliano
authors.affiliation: 1] Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA [2] Center for Marine Biotechnology and Biomedicine, University of California San Diego, La Jolla, CA, USA [3] Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
authors.forename: Pieter C
authors.initials: PC
authors.lastname: Dorrestein
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001709:Biotechnology / Q000379:methods; D057225:Data Mining; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods*; D006031:Glycosylation; D006868:Hydrolysis; D005810:Multigene Family; D013302:Streptomyces / Q000235:genetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents