title: Chemodiversity of Ladder-Frame Prymnesin Polyethers in Prymnesium parvum.
abstract: Blooms of the microalga Prymnesium parvum cause devastating fish kills worldwide, which are suspected to be caused by the supersized ladder-frame polyether toxins prymnesin-1 and -2. These toxins have, however, only been detected from P. parvum in rare cases since they were originally described two decades ago. Here, we report the isolation and characterization of a novel B-type prymnesin, based on extensive analysis of 2D- and 3D-NMR data of natural as well as 90% (13)C enriched material. B-type prymnesins lack a complete 1,6-dioxadecalin core unit, which is replaced by a short acyclic C2 linkage compared to the structure of the original prymnesins. Comparison of the bioactivity of prymnesin-2 with prymnesin-B1 in an RTgill-W1 cell line assay identified both compounds as toxic in the low nanomolar range. Chemical investigations by liquid chromatography high-resolution mass spectrometry (LC-HRMS) of 10 strains of P. parvum collected worldwide showed that only one strain produced the original prymnesin-1 and -2, whereas four strains produced the novel B-type prymnesin. In total 13 further prymnesin analogues differing in their core backbone and chlorination and glycosylation patterns could be tentatively detected by LC-MS/HRMS, including a likely C-type prymnesin in five strains. Altogether, our work indicates that evolution of prymnesins has yielded a diverse family of fish-killing toxins that occurs around the globe and has significant ecological and economic impact.
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark , Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.
authors.forename: Silas Anselm
authors.initials: SA
authors.lastname: Rasmussen
authors.affiliation: Department of Chemistry, Technical University of Denmark , Kemitorvet 207, 2800 Kgs. Lyngby, Denmark.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Meier
authors.affiliation: Marine Biological Section, Department of Biology, Copenhagen University , Strandpromenaden 5, 2100 Helsingør, Denmark.
authors.forename: Nikolaj Gedsted
authors.initials: NG
authors.lastname: Andersen
authors.affiliation: Marine Biological Section, Department of Biology, Copenhagen University , Strandpromenaden 5, 2100 Helsingør, Denmark.
authors.forename: Hannah Eva
authors.initials: HE
authors.lastname: Blossom
authors.affiliation: Department of Chemistry, Technical University of Denmark , Kemitorvet 207, 2800 Kgs. Lyngby, Denmark.
authors.forename: Jens Øllgaard
authors.initials: JØ
authors.lastname: Duus
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark , Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.
authors.forename: Kristian Fog
authors.initials: KF
authors.lastname: Nielsen
authors.affiliation: Marine Biological Section, Department of Biology, Copenhagen University , Strandpromenaden 5, 2100 Helsingør, Denmark.
authors.forename: Per Juel
authors.initials: PJ
authors.lastname: Hansen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark , Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.
authors.forename: Thomas Ostenfeld
authors.initials: TO
authors.lastname: Larsen
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000737:chemistry* / Q000302:isolation & purification*; D058087:Haptophyta / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D061065:Polyketides; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D011714:Pyrans / Q000737:chemistry* / Q000302:isolation & purification*
chemical_list: D006027:Glycosides; D008074:Lipoproteins; D061065:Polyketides; D011108:Polymers; D011714:Pyrans; C440216:prymnesin 1; C440215:prymnesin 2; C001884:prymnesin