Sulfo-Gambierones, Two New Analogs of Gambierone Produced by Gambierdiscus excentricus

Abstract

Ciguatera poisoning is caused by the ingestion of fish or shellfish contaminated with ciguatoxins produced by dinoflagellate species belonging to the genera Gambierdiscus and Fukuyoa. Unlike in the Pacific region, the species producing ciguatoxins in the Atlantic Ocean have yet to be definitely identified, though some ciguatoxins responsible for ciguatera have been reported from fish. Previous studies investigating the ciguatoxin-like toxicity of Atlantic Gambierdiscus species using Neuro2a cell-based assay identified G. excentricus as a potential toxin producer. To more rigorously characterize the toxin profile produced by this species, a purified extract from 124 million cells was prepared and partial characterization by high-resolution mass spectrometry was performed. The analysis revealed two new analogs of the polyether gambierone: sulfo-gambierone and dihydro-sulfo-gambierone. Algal ciguatoxins were not identified. The very low ciguatoxin-like toxicity of the two new analogs obtained by the Neuro2a cell-based assay suggests they are not responsible for the relatively high toxicity previously observed when using fractionated G. excentricus extracts, and are unlikely the cause of ciguatera in the region. These compounds, however, can be useful as biomarkers of the presence of G. excentricus due to their sensitive detection by mass spectrometry.

Characterization of New Gambierones Produced by Gambierdiscus balechii 1123M1M10

“…Four of them were tentatively proposed as novel compounds (desulfo-hydroxyl gambierone ( 2 ), 38-dehydroxy-12,13-dihydro-44-methylgambierone ( 3 ), 12,13-dihydro-44-methylgambierone ( 4 ) and 38-dehydroxy-44-methylgambierone ( 6 )) and were eluted at 5.35 min, 6.00 min, 6.01 min, and 6.29 min, respectively ( Figure 1 A). The other two compounds were proposed as gambierone ( 1 ) and 44-methylgambierone ( 5 ), based on the comparison of the fragmentation behaviors and retention times with the published data and standards [ 40 , 48 ]. The retention time of putative 44-methylgambierone was 6.28 min, consistent with the standard, while the putative gambierone (retention time: 5.26 min) was eluted earlier than the standard (retention time: 5.92 min) ( Figure 1 ).…”

“…In contrast to CTXs and MTXs, gambierone and its analogues are frequently found in Gambierdiscus species. For instance, except for three species ( G. scabrosus , G. carolinianus , and G. jejuensis ) with no information on NMR or HPLC-MS analyses of toxins, all reported Gambierdiscus species have been confirmed to produce gambierones [ 6 , 24 , 26 , 33 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Although gambierone and 44-methylgambierone are less toxic than CTXs, their extensive distribution proves their vital role [ 24 , 45 ].…”

“…Although gambierone and 44-methylgambierone are less toxic than CTXs, their extensive distribution proves their vital role [ 24 , 45 ]. Moreover, there are only four gambireones reported hitherto, including gambierone, 44-methylgambierone, and two partially identified sulfo-gambierones [ 8 , 39 , 40 ]. A lack of structural information and insufficient samples have limited the comprehensive evaluation of these toxins.…”

Occurrence of three dominant epibenthic dinoflagellates (Ostreopsis spp., Coolia monotis and Prorocentrum lima) in relation to biotic substrates and environmental factors in a highly dynamic ecosystem, the Strait of Gibraltar (Southwestern Mediterranean)

“…A screening of several toxic compound families was performed using a system composed of an ultrahigh-performance liquid chromatography (UHPLC) system (UFLC, Nexera, Shimadzu, Japan) coupled to a hybrid triple quadrupole-linear ion-trap mass spectrometer (API4000 QTRAP, Sciex, CA, USA) equipped with a TurboV source (ESI), according to the methods of Sibat et al ( 2018 ) for detection of ciguatoxins and Yon et al ( 2021 ) for the detection of maitotoxins and gambierones. The transitions monitored were either based on the literature (Nagai et al, 1992 ; Pisapia et al, 2017 ; Watanabe et al, 2013 ) or the result of optimization by infusion of available standards (only P-CTX3C and MTX1, Wako Chemicals).…”

Comparative Study on the Performance of Three Detection Methods for the Quantification of Pacific Ciguatoxins in French Polynesian Strains of Gambierdiscus polynesiensis

“…Subsequently, two additional species, F. paulensis and F. koreansis, were also identified [13][14][15]. These microalgae are able to produce a suite of polyketide secondary metabolites, including liposoluble compounds, i.e., ciguatoxins (CTXs) [16][17][18][19][20][21][22][23][24] versus more hydrosoluble compounds, i.e., maitotoxins (MTXs) [25][26][27][28][29][30][31][32][33][34][35][36], gambieric acids [37,38], gambierol [39,40], gambieroxide [41], and gambierones [42][43][44][45][46][47][48][49][50]. While CTXs and, to a lesser extent, MTXs, have been implicated in CP [51][52][53], it is not fully understood if the other metabolites could also play a role in CP, and most of them are considered compounds of interest due to their bioactivity and/or potential therapeutic applications [54][55][56][57]…”