Biosynthesis of 13-Desmethyl Spirolide C by the DinoflagellateAlexandriumostenfeldii

Abstract

Biosynthetic origins of the cyclic imine toxin 13-desmethyl spirolide C were determined by supplementing cultures of the toxigenic dinoflagellate Alexandrium ostenfeldii with stable isotope-labeled precursors [1,2-13C2]acetate, [1-13C]acetate, [2-13CD3]acetate, and [1,2-13C2,15N]glycine and measuring the incorporation patterns by 13C NMR spectroscopy. Despite partial scrambling of the acetate labels, the results show that most carbons of the macrocycle are polyketide-derived and that glycine is incorporated as an intact unit into the cyclic imine moiety. This work represents the first conclusive evidence that such cyclic imine toxins are polyketides and provides support for biosynthetic pathways previously defined for other polyether dinoflagellate toxins.

Identification of Fredericamycin E from Streptomyces griseus: Insights into Fredericamycin A Biosynthesis Highlighting Carbaspirocycle Formation

“…Biosynthetic experiments with 13-desmethylspirolide C implicate Diels-Alder chemistry for the production of the carbaspirocycle in the spirolides and related natural products such as pinnatoxin A, pteriatoxin A, and gymnodimine. 24 Related studies have been conducted with spirodionic acid supporting the potential relevance of Diels-Alder cycloadditions as a means of carbaspirocycle formation in natural products. 23 5 against HT-29 and MCF-7 cells relative to 1 suggests that the carbaspirocyclic fusion of rings C and D in both polyketides plays a larger role in cytotoxic activity than in the other tumor cell lines evaluated.…”

First direct fluorescence polarization assay for the detection and quantification of spirolides in mussel samples

“…Apart from some substituent radicals, the main differences found from spirolides class are the open imine ring from spirolide E and F and the unusual 5:6:6-trispiroketal ring system observed in spirolide G and its derivatives. This feature has not been found in other marine toxins [1] and its toxicity is not yet described. Nevertheless, the lack of the imine cyclic group in the spirolides E and F gives rise to a lack of toxicity in the mouse bioassay.…”

“…These toxins are members of the cyclic imine group that includes other compounds such as gymnodimine, pteriatoxins, pinnatoxins, prorocentrolide, spiro-prorocentrimine and symbioimines [1][2][3]. Spirolides were first identified in extracts of the digestive glands of mussels (Mytilus edulis) and scallops (Placopecten magellanicus) from the Atlantic coast of Nova Scotia, Canada, in 1991 [4].…”

“…However, spirolides have been detected in a great number of species and locations around the world. Apart from Canada, these toxins have been reported in USA (Gulf of Maine) [6], Spain [7], France [8], Italy [9], Scotland [10], Norway [11] and Denmark [1] and Chile [12]. Therefore, spirolides have a global distribution range and they may be a risk to human health around the world.…”

Complete 13C-labeling pattern of yessotoxin a marine ladder-frame polyether

“…Numerous efforts have been directed toward the synthesis of these marine natural products using various strategies, 2 but compared with such chemical studies, their biological aspects, such as mode of action and biosynthetic studies are not as well developed. Only a few biosynthetic studies of dinoflagellate metabolites have been reported about okadaic acid and its derivatives, 3 goniodomin, 4 amphidinolides, 5 13-desmethylspirolide C, 6 and amphidinols 7 whose structural features are classified into a polyether carboxylic acid, a macrolide, and a linear polyene-polyol. Interestingly, the 13 C incorporation patterns are unique and quite different from those of polyketides obtained from fungi and bacteria.…”