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.

Effects of Harmful Algal Blooms on Fish: Insights from Prymnesium parvum

“…, and 4: [7]), and Δ indicates results from this study. The prymnesins excreted [40] by P. parvum possess some membrane activity that causes gill damage [6][7][8]13]. The gill damage elicits the FATS gill irritant syndrome observed via oxygen consumption and ventilation rate shown here.…”

“…Thus, in contrast to the results obtained in this study that ranged from 1.28 to 24.80 h). In the case of P. parvum, studies showed that each strain of P. parvum likely produces slightly different types and amounts of prymnesins (A-, B-, and C-types), which are the substances suspected to be responsible for the ichthyotoxicity of P. parvum blooms [40]. This could explain why different strains of P. parvum express different toxicities [9] and could be the reason for the discrepancy between the results reported in this study (strain: UTEX-2797) and those previously reported by Bergmann et al [41] for an unknown strain.…”

“…The time to reach the 400,000 cells·mL −1 was approximately 2 weeks. At the time of the experiment, the proposed toxins (the prymnesins [38]), were unquantifiable [39,40]. Whether prymnesins are the sole toxins in a P. parvum bloom is debatable, so controlling for prymnesin content might confound the effects of other unknown toxins [7,8,[40][41][42][43].…”

“…Whether prymnesins are the sole toxins in a P. parvum bloom is debatable, so controlling for prymnesin content might confound the effects of other unknown toxins [7,8,[40][41][42][43]. Significant variations in toxicity have been reported when exposing fish externally to P. parvum culture [8,40]. The P. parvum toxicity has been reported to vary with pH [7,43], temperature, adsorbents, oxidizing agents [43], and mechanical disturbance [44].…”

Isolation and Characterization of a Double Stranded DNA Megavirus Infecting the Toxin-Producing Haptophyte Prymnesium parvum

“…However, the toxic metabolites responsible for bloom toxicity are not established in Heterosigma akashiwo , making studies of viral impact on toxicity difficult. On the other hand, reports of toxic P. parvum metabolites are numerous and include fatty acids [48], glycerolipids [49] and very large ladder-frame polyether toxins, known collectively as the prymnesins [50,51,52]. Reports of cases of toxic and non-toxic blooms of Prymnesium and other harmful algal species [37] has led to speculation that an ecological trigger exists for toxicity.…”