Development of a data dependent acquisition-based approach for the identification of unknown fast-acting toxins and their ester metabolites

Varriale, Fabio; Tartaglione, Luciana; Cinti, Stefano; Milandri, Anna; Dall’Ara, Sonia; Calfapietra, Anna

doi:10.1016/j.talanta.2020.121842

Cited by 13 publications

(10 citation statements)

References 33 publications

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“…The fragmentation spectra found coincide perfectly with those reported by Harju et al [11], Martens et al [12], and Zurhelle et al [5] for these compounds in A. ostenfeldii. Up to now, the only GYMs found in shellfish have been GYM A in New Zealand [2], Tunisia [23,24], South Africa [25], China [26], Italy [27], France [28], and Spain [29]; GYM B just in Tunisia [23,24]; and supposed GYM G, GYM H, GYM I, GYM J, GYM F, 5 isobaric analogues of GYM B/C, and some ester metabolites of GYMs in a pool of Mediterranean samples [30]. As far as we know, there is no report of the presence of GYM D or 16-desmethyl GYM D in shellfish.…”

Section: Discussionmentioning

confidence: 99%

First Report of Two Gymnodimines and Two Tetrodotoxin Analogues in Invertebrates from the North Atlantic Coast of Spain

Rossignoli¹,

Mariño²,

Martín³

et al. 2023

Marine Drugs

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Gymnodimine D (GYM D), 16-desmethyl gymnodimine D (16-desmethyl GYM D), and two tetrodotoxin analogues have been found in invertebrates obtained from the north Atlantic coast of Spain from May 2021 to October 2022. It is the first report of GYMD and 16-desmethyl GYM D in invertebrates worldwide and of the tetrodotoxin analogues, 5,6,11 trideoxy tetrodotoxin (5,6,11 trideoxy TTX) and its isomer (referred to as 5,6,11 trideoxy-epi-TTX), in the north Atlantic Coast of Spain. In this study, we also report for the first time the detection of tetrodotoxin (TTX) in three species (the cnidaria Calliactis parasitica, an unidentified species, and the bivalve Tellina donacina). The prevalence was medium for GYM D and 16-desmethyl GYM D and low for TTXs overall. The concentrations recorded were variable, with maximum values of GYM D in the bivalve Cerastoderma edule (8.8 μg GYM A equivalents kg−1), of 16-desmethyl GYM D in the bivalve Magellana gigas (10 μg GYM A equivalents kg−1) and of TTX and 5,6,11 trideoxy TTX in the cnidaria C. parasitica (49.7 and 233 μg TTX equivalents kg−1, respectively). There is very scarce information about these compounds. Therefore, the reporting of these new detections will increase the knowledge on the current incidence of marine toxins in Europe that the European Food Safety Authority (EFSA), in particular, and the scientific community, in general, have. This study also highlights the importance of analyzing toxin analogues and metabolites for effective monitoring programs and adequate health protection.

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Section: Discussionmentioning

confidence: 99%

First Report of Two Gymnodimines and Two Tetrodotoxin Analogues in Invertebrates from the North Atlantic Coast of Spain

Rossignoli¹,

Mariño²,

Martín³

et al. 2023

Marine Drugs

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“…Various LC–MS/MS methods have been developed by the advancement of technology. For example, the establishment of the liquid chromatography–high-resolution mass spectrometry (LC–HRMS) approach is conducive to the discovery of new derivatives of GYMs and the in-depth investigation of the metabolic characteristics of shellfish samples [ 36 ]. The combination of the dispersive liquid–liquid microextraction (DLLME) with the liquid chromatography with triple quadrupole mass spectrometry (LC–QqQ-MS/MS) allowed for the sensitive and selective analysis of thirteen lipophilic marine toxins, including GYM in seawater samples [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

Selection, Characterization, and Optimization of DNA Aptamers against Challenging Marine Biotoxin Gymnodimine-A for Biosensing Application

Zhang

Gao²,

Deng³

et al. 2022

Toxins

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Gymnodimines (GYMs), belonging to cyclic imines (CIs), are characterized as fast-acting toxins, and may pose potential risks to human health and the aquaculture industry through the contamination of sea food. The existing detection methods of GYMs have certain defects in practice, such as ethical problems or the requirement of complicated equipment. As novel molecular recognition elements, aptamers have been applied in many areas, including the detection of marine biotoxins. However, GYMs are liposoluble molecules with low molecular weight and limited numbers of chemical groups, which are considered as “challenging” targets for aptamers selection. In this study, Capture-SELEX was used as the main strategy in screening aptamers targeting gymnodimine-A (GYM-A), and an aptamer named G48nop, with the highest KD value of 95.30 nM, was successfully obtained by screening and optimization. G48nop showed high specificity towards GYM-A. Based on this, a novel aptasensor based on biolayer interferometry (BLI) technology was established in detecting GYM-A. This aptasensor showed a detection range from 55 to 1400 nM (linear range from 55 to 875 nM) and a limit of detection (LOD) of 6.21 nM. Spiking experiments in real samples indicated the recovery rate of this aptasensor, ranging from 96.65% to 109.67%. This is the first study to report an aptamer with high affinity and specificity for the challenging marine biotoxin GYM-A, and the new established aptasensor may be used as a reliable and efficient tool for the detection and monitoring of GYMs in the future.

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“…15−20 and sensitivity of current mass spectrometers can overcome the limited chromatographic resolution between biotoxin analogues and the need to work with large volumes of culture. Against all odds, the study of dinoflagellates by dereplication using LC-HRMS has not attempted except for a few recent studies, 20,21 although it could ignite compound discovery programs by facilitating the selection of the best candidate strains to undergo biotechnological processes. The current main bottleneck of LC-HRMS n dereplication approaches is the lack of experimental reference data.…”

Section: ■ Introductionmentioning

confidence: 99%

Rapid Screening of Polyol Polyketides from Marine Dinoflagellates

et al. 2022

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Dinoflagellate-derived polyketides are typically large molecules (>1000 Da) with complex structures, potent bioactivities, and high toxicities. Their discovery suffers three major bottlenecks: insufficient bioavailability, low-yield cultivation of producer organisms, and production of multiple highly related analogues by a single strain. Consequently, the biotechnological production of therapeutics or toxicological standards of dinoflagellate-derived polyketides is also hampered. Strategies based on sensitive and selective techniques for chemical prospection of dinoflagellate extracts could aid in overcoming these limitations, as it allows selecting the most interesting candidates for discovery and exploitation programs according to the biosynthetic potential. In this work, we assess the combination of data-dependent liquid chromatography coupled with high-resolution tandem mass spectrometry (LC–HRMS2) and molecular networking to screen polyol polyketides. To demonstrate the power of this approach, we selected dinoflagellate Amphidinium carterae since it is commonly used as a biotechnological model and produces amphidinols, a family of polyol-polyene compounds with antifungal and antimycoplasmal activity. First, we screened families of compounds with multiple hydroxyl groups by examining MS2 profiles that contain sequential neutral losses of water. Then, we clustered MS2 spectra by molecular networking to facilitate the dereplication and discovery of amphidinols. Finally, we used the MS2 fragmentation behavior of well-characterized luteophanol D as a model to propose a structural hypothesis of nine novel amphidinols. We envision that this strategy is a valuable approach to rapidly monitoring toxin production of known and unknown polyol polyketides in dinoflagellates, even in small culture volumes, and distinguishing strains according to their toxin profiles.

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Development of a data dependent acquisition-based approach for the identification of unknown fast-acting toxins and their ester metabolites

Cited by 13 publications

References 33 publications

First Report of Two Gymnodimines and Two Tetrodotoxin Analogues in Invertebrates from the North Atlantic Coast of Spain

First Report of Two Gymnodimines and Two Tetrodotoxin Analogues in Invertebrates from the North Atlantic Coast of Spain

Selection, Characterization, and Optimization of DNA Aptamers against Challenging Marine Biotoxin Gymnodimine-A for Biosensing Application

Rapid Screening of Polyol Polyketides from Marine Dinoflagellates

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