title: Discovery of the antibiotic phosacetamycin via a new mass spectrometry-based method for phosphonic acid detection.
abstract: Naturally occurring phosphonates such as phosphinothricin (Glufosinate, a commercially used herbicide) and fosfomycin (Monurol, a clinically used antibiotic) have proved to be potent and useful biocides. Yet this class of natural products is still an under explored family of secondary metabolites. Discovery of the biosynthetic pathways responsible for the production of these compounds has been simplified by using gene based screening approaches, but detection and identification of the natural products the genes produce have been hampered by a lack of high-throughput methods for screening potential producers under various culture conditions. Here, we present an efficient mass-spectrometric method for the selective detection of natural products containing phosphonate and phosphinate functional groups. We have used this method to identify a new phosphonate metabolite, phosacetamycin, whose structure, biological activity, and biosynthetic gene cluster are reported.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Evans
authors.forename: Changming
authors.initials: C
authors.lastname: Zhao
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Gao
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Evans
authors.forename: Kou-San
authors.initials: KS
authors.lastname: Ju
authors.forename: James R
authors.initials: JR
authors.lastname: Doroghazi
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
authors.forename: Neil L
authors.initials: NL
authors.lastname: Kelleher
authors.forename: William W
authors.initials: WW
authors.lastname: Metcalf
mesh_terms: D000081:Acetamides / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology*; D053898:Biosynthetic Pathways / Q000235:genetics; D002846:Chromatography, Affinity / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004926:Escherichia coli / Q000187:drug effects; D016680:Genome, Bacterial; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D010710:Phosphates / Q000302:isolation & purification; D010757:Phosphorous Acids / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D010710:Phosphates; D010757:Phosphorous Acids; C585896:phosacetamycin; C570063:phosphonic acid