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1.
J Agric Food Chem ; 68(5): 1427-1435, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31913622

RESUMO

A number of new C-11 hydroxyl metabolites (so-called M-toxins) of paralytic shellfish toxins (PSTs) have been discovered in contaminated shellfish, and trace amounts have also been detected in some strains of PST-producing microalgae. To investigate the chemical conversion and stability of M-toxins, mussel extracts were purified with solid-phase extraction cartridges (Oasis HLB) and Biogel P-2 resin columns and four partially purified M-toxin fractions were stored at different temperatures (-20, 4, and 20 °C) and pH values (3, 4, and 5). The concentrations and profiles of M-toxins in these fractions were analyzed using liquid chromatography coupled with tandem mass spectrometry for 27 weeks. Results further confirmed the chemical conversion pathway M1 → M3 → M5 and determined for the first time two new transformation pathways: M2 → M4 → M6 and neosaxitoxin (NEO) → M10. The half-lives of M1, M2, M4, and M10 were calculated using a first-order degradation kinetics model, which indicated that the degradation of all M-toxins was dependent upon the temperature and pH, increasing with rising temperature and pH. In comparison to M4 and M10, M1 was more sensitive to the temperature, followed by M2. Results suggest that M-toxins should be maintained at a low temperature (-20 °C) and low pH (3) for their prolonged storage. M-toxins were less stable than all of the common analogues of PSTs, which may be beneficial for shellfish to achieve rapid detoxification through transformation of PSTs to M-toxins. These new findings are of significance because they enable further understanding of the metabolism of PSTs and their detoxification mechanisms in contaminated shellfish.


Assuntos
Bivalves/química , Toxinas Marinhas/química , Frutos do Mar/toxicidade , Animais , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos/análise , Concentração de Íons de Hidrogênio , Toxinas Marinhas/toxicidade , Estrutura Molecular , Frutos do Mar/análise , Espectrometria de Massas em Tandem , Temperatura Ambiente
2.
J Agric Food Chem ; 67(46): 12911-12917, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31647661

RESUMO

Tetrodotoxin and its analogues are the causative toxins of pufferfish poisoning. Tetrodotoxin has been recently detected in bivalve mollusks collected in New Zealand and Europe, highlighting the need to include tetrodotoxin in monitoring programs for bivalves by instrumental methods. In the present study, tetrodotoxin and its analogues in commercially available tetrodotoxin reagents were quantitated accurately by quantitative 1H-nuclear magnetic resonance (qNMR) spectroscopy. The results were applied to estimate relative molar responses of tetrodotoxin and its analogues in hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC/MS/MS). All four components (tetrodotoxin hemilactal form (1), tetrodotoxin 10,7-lactone form (2), 4-epitetrodotoxin (3), and 4,9-anhydrotetrodotoxin (4)) generated by equilibrating tetrodotoxin in aqueous solution were prepared as a mixture. From the HSQC spectrum of the mixture, the separated signals derived from three components, excluding 1, were selected and used for the quantitation. In addition, the relative molar responses of 3 and 4 on HILIC/MS/MS were calculated to be 0.73 and 0.46, respectively. These values could be useful for quantitation of 3 and 4 using the tetrodotoxin standard by HILIC/MS/MS. Our results also indicate that qNMR is useful for preparation of tetrodotoxin certified reference material.


Assuntos
Cromatografia Líquida/métodos , Espectroscopia de Ressonância Magnética/métodos , Toxinas Marinhas/química , Espectrometria de Massas em Tandem/métodos , Tetrodotoxina/química , Animais , Estrutura Molecular , Tetraodontiformes
3.
Ecotoxicology ; 28(9): 1085-1104, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559558

RESUMO

Many species of marine life in southwestern Florida, including sea turtles, are impacted by blooms of the toxic dinoflagellate, Karenia brevis. Sublethal exposure to toxins produced by K. brevis has been shown to impact sea turtle health. Since all sea turtles in the Gulf of Mexico have protected status, a freshwater turtle, Trachemys scripta, was used as a model for immune system effects following experimental exposure to a predominant brevetoxin congener in K. brevis blooms, PbTx-3. Exposure to PbTx-3 was oral or intratracheal and health effects were assessed using a suite of immune function parameters: innate immune function (phagocytosis, plasma lysozyme activity), adaptive immune function (lymphocyte proliferation), and measures of oxidative stress (superoxide dismutase (SOD) and glutathione-S-transferase (GST) activity in plasma). Inflammation was also measured using plasma protein electrophoresis. In addition, differential expression of genes in peripheral blood leukocytes was determined using suppression subtractive hybridization followed by real-time PCR of specific genes. The primary immune effects of sublethal brevetoxin exposure in T. scripta following PbTx-3 administration, appear to be an increase in oxidative stress, a decrease in lysozyme activity, and modulation of immune function through lymphocyte proliferation responses. Plasma protein electrophoresis showed a decreased A:G ratio which may indicate potential inflammation. Genes coding for oxidative stress, such as thioredoxin and GST, were upregulated in exposed animals. That sublethal brevetoxin exposures impact immune function components suggests potential health implications for sea turtles naturally exposed to toxins. Knowledge of physiological stressors induced by brevetoxins may contribute to the ultimate goal of developing directed treatment strategies in exposed animals for reduced mortality resulting from red tide toxin exposure in sea turtles.


Assuntos
Imunidade Inata/efeitos dos fármacos , Toxinas Marinhas/toxicidade , Tartarugas/fisiologia , Animais , Toxinas Marinhas/química , Oxocinas/química , Testes de Toxicidade
4.
Mar Drugs ; 17(6)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159276

RESUMO

Currently a few compounds isolated from marine sources have become drugs, mainly directed towards cancer and pain. Compounds from marine sources have exquisite potencies against eukaryotic cells, as they act as protective agents against attack by predators in the marine environment. Their toxicities act as a "double-edged sword" as they are often too toxic for direct use in humans and thus have to be chemically modified. By linking suitably modified compounds to monoclonal antibodies directed against specific epitopes in mammalian cancer cells, they can be delivered to a specific cell type in humans. This review updates and extends an article published in early 2017, demonstrating how by careful chemical modifications, highly toxic compounds, frequently peptidic in nature, can be utilized as antitumor drug candidates. The antibody-drug- conjugates (ADCs) discussed are those that are currently in clinical trials listed in the NIH Clinical Trials Registry as, "currently active, recruiting or in some cases, recently completed". There are also some ADCs discussed that are at the advanced preclinical stage, that in some cases, are repurposing current drug entities, and the review finishes with a short discussion of the aplyronines as potential candidate warheads as a result of scalable synthetic processes.


Assuntos
Toxinas Marinhas/química , Toxinas Marinhas/uso terapêutico , Neoplasias/tratamento farmacológico , Analgésicos/química , Analgésicos/uso terapêutico , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Humanos , Imunoconjugados/uso terapêutico , Dor/tratamento farmacológico
5.
Mar Drugs ; 17(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31159357

RESUMO

Sea anemones produce venoms of exceptional molecular diversity, with at least 17 different molecular scaffolds reported to date. These venom components have traditionally been classified according to pharmacological activity and amino acid sequence. However, this classification system suffers from vulnerabilities due to functional convergence and functional promiscuity. Furthermore, for most known sea anemone toxins, the exact receptors they target are either unknown, or at best incomplete. In this review, we first provide an overview of the sea anemone venom system and then focus on the venom components. We have organised the venom components by distinguishing firstly between proteins and non-proteinaceous compounds, secondly between enzymes and other proteins without enzymatic activity, then according to the structural scaffold, and finally according to molecular target.


Assuntos
Venenos de Cnidários/química , Venenos de Cnidários/classificação , Toxinas Marinhas/química , Toxinas Marinhas/classificação , Animais , Modelos Moleculares , Anêmonas-do-Mar/química
6.
Mar Drugs ; 17(5)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052268

RESUMO

Prorocentrum lima is a typical benthic toxic dinoflagellate, which can produce phycotoxins such as okadaic acid (OA). In this study, we identified three ABC transporter genes (ABCB1, ABCC1 and ABCG2) and characterized their expression patterns, as well as OA production under different environmental conditions in P. lima. We found that the three ABC transporters all showed high identity with related ABC proteins from other species, and contained classical features of ABC transport proteins. Among them, ABCG2 was a half size transporter. The three ABC transporter genes displayed various expression profiles under different conditions. The high concentration of Cu2+ could up-regulate ABCB1, ABCC1 and ABCG2 transcripts in P. lima, suggesting the potential defensive role of ABC transporters against metal ions in surrounding waters. Cu2+, in some concentration, could induce OA production; meanwhile, tributyltin inhibited OA accumulation. The grazer Artemia salina could induce OA production, and P. lima displayed some toxicity to the grazer, indicating the possibility of OA as an anti-grazing chemical. Collectively, our results revealed intriguing data about OA production and the expression patterns of three ABC transporter genes. However, we could not find any significant correlation between OA production and expression pattern of the three ABC transporters in P. lima. Our results might provide new molecular insights on the defensive responses of P. lima to the surrounding environment.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Dinoflagelados/metabolismo , Dinoflagelados/crescimento & desenvolvimento , Meio Ambiente , Toxinas Marinhas/química , Ácido Okadáico/metabolismo , RNA Mensageiro
7.
Toxicon ; 164: 44-50, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954452

RESUMO

Compounds similar to maitotoxin (MTX) have been isolated from several laboratory strains of the dinoflagellate Gambierdiscus spp. from the Caribbean. Mass spectral results suggest that these compounds differ from MTX by the loss of one sulfate group and, in some cases, the loss of one methyl group with the addition of one degree of unsaturation. NMR experiments, using approximately 50 nmol of one of these compounds, have demonstrated that the 9-sulfo group of MTX is still present, suggesting that these compounds are 40-desulfo congeners of MTX.


Assuntos
Dinoflagelados/química , Toxinas Marinhas/química , Oxocinas/química , Região do Caribe , Cromatografia Líquida , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular
8.
Mar Drugs ; 17(4)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965587

RESUMO

A novel protein, soritesidine (SOR) with potent toxicity was isolated from the marine sponge Spongosorites sp. SOR exhibited wide range of toxicities over various organisms and cells including brine shrimp (Artemia salina) larvae, sea hare (Aplysia kurodai) eggs, mice, and cultured mammalian cells. Toxicities of SOR were extraordinary potent. It killed mice at 5 ng/mouse after intracerebroventricular (i.c.v.) injection, and brine shrimp and at 0.34 µg/mL. Cytotoxicity for cultured mammalian cancer cell lines against HeLa and L1210 cells were determined to be 0.062 and 12.11 ng/mL, respectively. The SOR-containing fraction cleaved plasmid DNA in a metal ion dependent manner showing genotoxicity of SOR. Purified SOR exhibited molecular weight of 108.7 kDa in MALDI-TOF MS data and isoelectric point of approximately 4.5. N-terminal amino acid sequence up to the 25th residue was determined by Edman degradation. Internal amino acid sequences for fifteen peptides isolated from the enzyme digest of SOR were also determined. None of those amino acid sequences showed similarity to existing proteins, suggesting that SOR is a new proteinous toxin.


Assuntos
Toxinas Marinhas/toxicidade , Poríferos , Sequência de Aminoácidos , Animais , Aplysia/efeitos dos fármacos , Artemia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Bioensaio/métodos , Linhagem Celular Tumoral , Humanos , Japão , Larva/efeitos dos fármacos , Masculino , Toxinas Marinhas/administração & dosagem , Toxinas Marinhas/química , Toxinas Marinhas/isolamento & purificação , Camundongos , Peso Molecular , Testes de Mutagenicidade/métodos
9.
Artigo em Inglês | MEDLINE | ID: mdl-30724672

RESUMO

Okadaic acid group (OA-group) is a set of lipophilic toxins which are characterised by being produced by species associated with the genera Dinophysis and Prorocentrum. OA-group has been regularly detected in endemic shellfish species from the southern zone of Chile only through the mouse bioassay. The purpose of this work was to determine the variability of OA-group toxins in endemic aquatic organisms (bivalves, crabs, gastropods and fish) and to establish the relationship with the concentration of fatty acids (FAs) detected in the evaluated species. The toxicity of OA-group and the FA profiles were determined using LC-MS/MS and gas chromatography with flame-ionisation detection, respectively. In the study area, the dinoflagellate Dinophysis acuta was detected in densities ≈2000 cells ml-1 with a toxicity ≈18.3 pg OA equiv cel-1. The analysis identified OA and dinophysistoxin-1 in shellfish in a range of ≈90 to ≈225 µg OA eq kg-1, where no toxins in fish were detected. A positive relationship between the FA level and the concentration of OA-group toxins in the digestive glands of bivalves and gastropods was established, noted for high levels of saturated FAs (C14:0 and C16:0). The toxic variability of OA-group toxins determined in the different species allowed us to establish that the consumption of these vectors, regulated by non-analytical methods, can be harmful when consumed by humans, thus suggesting that the sanitary regulations for the control of OA-group in Chile should be updated.


Assuntos
Organismos Aquáticos/química , Ácidos Graxos/análise , Toxinas Marinhas/química , Toxinas Marinhas/toxicidade , Ácido Okadáico/química , Ácido Okadáico/toxicidade , Animais , Bivalves/química , Braquiúros/química , Cromatografia Líquida , Peixes , Gastrópodes/química , Especificidade da Espécie , Espectrometria de Massas em Tandem
10.
Toxins (Basel) ; 11(2)2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717108

RESUMO

Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification of a structural homologue of the recently described gambierone isolated from the same strain. The structure was elucidated mainly by comparison of NMR and MS data with those of gambierone and ascertained by 2D NMR data analyses. Gratifyingly, a close inspection of the MS data of the new 44-methylgambierone suggests that this toxin would actually correspond to the structure of maitotoxin-3 (MTX3, m/z 1039.4957 for the protonated adduct) detected in 1994 in a Pacific strain of Gambierdiscus and recently shown in routine monitoring programs. Therefore, this work provides for the first time the chemical identification of the MTX3 molecule by NMR. Furthermore, biological data confirmed the similar activities of both gambierone and 44-methylgambierone. Both gambierone and MTX3 induced a small increase in the cytosolic calcium concentration but only MTX3 caused cell cytotoxicity at micromolar concentrations. Moreover, chronic exposure of human cortical neurons to either gambierone or MTX3 altered the expression of ionotropic glutamate receptors, an effect already described before for the synthetic ciguatoxin CTX3C. However, even when gambierone and MTX3 affected glutamate receptor expression in a similar manner their effect on receptor expression differed from that of CTX3C, since both toxins decreased AMPA receptor levels while increasing N-methyl-d-aspartate (NMDA) receptor protein. Thus, further studies should be pursued to clarify the similarities and differences in the biological activity between the known ciguatoxins and the new identified molecule as well as its contribution to the neurological symptoms of ciguatera.


Assuntos
Toxinas Marinhas/química , Toxinas Marinhas/farmacologia , Oxocinas/química , Oxocinas/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciguatoxinas/farmacologia , Dinoflagelados , Éteres/química , Éteres/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Receptores de Glutamato/metabolismo
11.
Toxicon ; 159: 32-37, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30659862

RESUMO

Searching for Amnesic (ASP), Paralytic (PSP) and Lipophilic (LT) toxins in seafood is of great importance for consumer protection. Studies are usually focused on the most aquacultured species, the mussel. But, there are a number of potentially commercially important shellfish species as rough cockle Acanthocardia tuberculata (Linnaeus, 1758) and smooth clam Callista chione (Linnaeus, 1758) which are common in the Croatian Adriatic Sea. Investigation of marine biotoxins accumulation in these two species of shellfish from the Adriatic Sea has not been conducted up to now. In order to detect the potential marine biotoxin profile of A. tuberculata and C. chione wild populations, samples were taken monthly during one-year survey from the estuarine area in the central Adriatic Sea. HPLC-FLD with pre-column oxidation and HPLC-UV-DAD methods were employed for PSP and ASP toxins determination, respectively, while LTs were determined by LC-MS/MS. This research had revealed the differences in the accumulation of ASP, PSP and LT toxins between the two studied species, as Acanthocardia tuberculata showed more diverse profile with higher concentrations of analysed toxins. Both investigated shellfish species had shown levels of these biotoxins under the legal limits set by the European Commission.


Assuntos
Bivalves/química , Cardiidae/química , Toxinas Marinhas/análise , Animais , Monitoramento Ambiental , Humanos , Toxinas Marinhas/química , Região do Mediterrâneo , Oceanos e Mares , Estações do Ano , Frutos do Mar , Intoxicação por Frutos do Mar/prevenção & controle
12.
Org Lett ; 21(2): 356-359, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30601015

RESUMO

Azaspiracid-34 (AZA34) is a recently described structurally unique member of the azaspiracid class of marine neurotoxins. Its novel structure, tentatively assigned on the basis of MS and 1H NMR spectroscopy, is accompanied by a 5.5-fold higher level of toxicity against Jurkat T lymphocytes than AZA1. To completely assign the structure of AZA34 and provide material for in-depth biological evaluation and detection, synthetic access to AZA34 was targeted. This began with the convergent and stereoselective assembly of the C1-C19 domain of AZA34 designed to dovetail with the recent total synthesis approach to AZA3.


Assuntos
Células Jurkat/citologia , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Compostos de Espiro/síntese química , Humanos , Células Jurkat/química , Espectroscopia de Ressonância Magnética , Toxinas Marinhas/síntese química , Toxinas Marinhas/química , Estrutura Molecular , Compostos de Espiro/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-30476593

RESUMO

The activities of two effectors, brevetoxin (PbTx) and manumycin-A (Man-A), of thioredoxin reductase (TrxR) have been evaluated against a series of fourteen TrxR orthologs originating from mammals, insects and protists and several mutants. Man-A, a molecule with numerous electrophilic sites, forms a covalent adduct with most selenocystine (Sec)-containing TrxR enzymes. The evidence also demonstrates that Man-A can form covalent adducts with some non-Sec-containing enzymes. The activities of TrxR enzymes towards various substrates are moderated by Man-A either positively or negatively depending on the enzyme. In general, the reduction of substrates by Sec-containing TrxR is inhibited and NADPH oxidase activity is activated. For non-Sec-containing TrxR the effect of Man-A on the reduction of substrates is variable, but NADPH oxidase activity can be activated even in the absence of covalent modification of TrxR. The effect of PbTx is less pronounced. A smaller subset of enzymes is affected by PbTx. With a single exception, the activities of most of this subset are activated. Although both PbTx variants can react with selenocysteine, a stable covalent adduct is not formed with any of the TrxR enzymes. The key findings from this work are (i) the identification of an alternate mechanism of toxicity for the algal toxin brevetoxin (ii) the demonstration that covalent modification of TrxR is not a prerequisite for the activation of NADPH oxidase activity of TrxR and (iii) the identification of an inhibitor which can discriminate between cytosolic and mitochondrial TrxR.


Assuntos
Toxinas Marinhas/farmacologia , Oxocinas/farmacologia , Polienos/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Tiorredoxina Dissulfeto Redutase/metabolismo , Animais , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Insetos , Mamíferos , Toxinas Marinhas/química , NADPH Oxidases/metabolismo , Oxocinas/química , Polienos/química , Alcamidas Poli-Insaturadas/química , Especificidade da Espécie , Tiorredoxinas/metabolismo
15.
Mar Drugs ; 16(11)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441860

RESUMO

Cyclic imine toxins are neurotoxic, macrocyclic compounds produced by marine dinoflagellates. Mass spectrometric screenings of extracts from natural plankton assemblages revealed a high chemical diversity among this toxin class, yet only few toxins are structurally known. Here we report the structural characterization of four novel cyclic-imine toxins (two gymnodimines (GYMs) and two spirolides (SPXs)) from cultures of Alexandrium ostenfeldii. A GYM with m/z 510 (1) was identified as 16-desmethylGYM D. A GYM with m/z 526 was identified as the hydroxylated degradation product of (1) with an exocyclic methylene at C-17 and an allylic hydroxyl group at C-18. This compound was named GYM E (2). We further identified a SPX with m/z 694 as 20-hydroxy-13,19-didesmethylSPX C (10) and a SPX with m/z 696 as 20-hydroxy-13,19-didesmethylSPX D (11). This is the first report of GYMs without a methyl group at ring D and SPXs with hydroxyl groups at position C-20. These compounds can be conceived as derivatives of the same nascent polyketide chain, supporting the hypothesis that GYMs and SPXs are produced through common biosynthetic genes. Both novel GYMs 1 and 2 were detected in significant amounts in extracts from natural plankton assemblages (1: 447 pg; 2: 1250 pg; 11: 40 pg per mL filtered seawater respectively).


Assuntos
Dinoflagelados/química , Compostos Heterocíclicos com 3 Anéis/química , Hidrocarbonetos Cíclicos/química , Iminas/química , Toxinas Marinhas/química , Fitoplâncton/química , Compostos de Espiro/química , Compostos Heterocíclicos com 3 Anéis/isolamento & purificação , Hidrocarbonetos Cíclicos/isolamento & purificação , Iminas/isolamento & purificação , Toxinas Marinhas/isolamento & purificação , Estrutura Molecular , Compostos de Espiro/isolamento & purificação
16.
Yakugaku Zasshi ; 138(11): 1335-1344, 2018.
Artigo em Japonês | MEDLINE | ID: mdl-30381641

RESUMO

Marine natural products and biologically active compounds often contain cyclic ether units. Thus, regio- and stereoselective construction of these structures has long been a topic of interest in organic synthesis. This review summarizes new synthetic approaches to polycyclic ether natural products utilizing the features of chemical elements.


Assuntos
Produtos Biológicos/síntese química , Elementos , Éteres Cíclicos/síntese química , Biologia Marinha , Toxinas Marinhas/síntese química , Oxocinas/síntese química , Animais , Produtos Biológicos/química , Catálise , Química Orgânica/métodos , Éteres Cíclicos/química , Ouro , Interações Hidrofóbicas e Hidrofílicas , Toxinas Marinhas/química , Camundongos , Conformação Molecular , Fenômenos de Química Orgânica , Oxocinas/química , Rênio/química , Estereoisomerismo
17.
Mar Drugs ; 16(11)2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30366463

RESUMO

Blue biotechnologies implement marine bio-resources for addressing practical concerns. The isolation of biologically active molecules from marine animals is one of the main ways this field develops. Strikingly, cnidaria are considered as sustainable resources for this purpose, as they possess unique cells for attack and protection, producing an articulated cocktail of bioactive substances. The Mediterranean sea anemone Anemonia viridis has been studied extensively for years. In this short review, we summarize advances in bioprospecting of the A. viridis toxin arsenal. A. viridis RNA datasets and toxin data mining approaches are briefly described. Analysis reveals the major pool of neurotoxins of A. viridis, which are particularly active on sodium and potassium channels. This review therefore integrates progress in both RNA-Seq based and biochemical-based bioprospecting of A. viridis toxins for biotechnological exploitation.


Assuntos
Venenos de Cnidários/química , Venenos de Cnidários/genética , Toxinas Marinhas/química , Neurotoxinas/química , Neurotoxinas/genética , Anêmonas-do-Mar/química , Anêmonas-do-Mar/genética , Animais , Venenos de Cnidários/isolamento & purificação , Venenos de Cnidários/farmacologia , Mineração de Dados , Toxinas Marinhas/genética , Toxinas Marinhas/isolamento & purificação , Toxinas Marinhas/farmacologia , Neurotoxinas/isolamento & purificação , Neurotoxinas/farmacologia , RNA/química , RNA/genética , Análise de Sequência de RNA , Pesquisa Médica Translacional
18.
J Am Chem Soc ; 140(37): 11863-11869, 2018 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-30192526

RESUMO

The remarkable degree of synthetic selectivity found in Nature is exemplified by the biosynthesis of paralytic shellfish toxins such as saxitoxin. The polycyclic core shared by saxitoxin and its relatives is assembled and subsequently elaborated through the installation of hydroxyl groups with exquisite precision that is not possible to replicate with traditional synthetic methods. Here, we report the identification of the enzymes that carry out a subset of C-H functionalizations involved in paralytic shellfish toxin biosynthesis. We have shown that three Rieske oxygenases mediate hydroxylation reactions with perfect site- and stereoselectivity. Specifically, the Rieske oxygenase SxtT is responsible for selective hydroxylation of a tricyclic precursor to the famous natural product saxitoxin, and a second Rieske oxygenase, GxtA, selectively hydroxylates saxitoxin to access the oxidation pattern present in gonyautoxin natural products. Unexpectedly, a third Rieske oxygenase, SxtH, does not hydroxylate tricyclic intermediates, but rather a linear substrate prior to tricycle formation, rewriting the biosynthetic route to paralytic shellfish toxins. Characterization of SxtT, SxtH, and GxtA is the first demonstration of enzymes carrying out C-H hydroxylation reactions in paralytic shellfish toxin biosynthesis. Additionally, the reactions of these oxygenases with a suite of saxitoxin-related molecules are reported, highlighting the substrate promiscuity of these catalysts and the potential for their application in the synthesis of natural and unnatural saxitoxin congeners.


Assuntos
Toxinas Marinhas/biossíntese , Frutos do Mar , Animais , Hidroxilação , Toxinas Marinhas/química , Modelos Moleculares , Estrutura Molecular
19.
Harmful Algae ; 78: 1-8, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30196917

RESUMO

Three strains of the toxic benthic dinoflagellate Prorocentrum hoffmannianum were isolated in the Canary Islands (north-east Atlantic Ocean, Spain). The identity of the strains was determined by phylogenetic analyses of partial LSU rDNA (D1-D2 regions) but their morphology based on SEM images corresponded to P. maculosum. Their toxin profiles were analyzed by liquid chromatography and high resolution mass spectrometry analysis (LC-HRMS) on cell extracts and culture media. Okadaic acid and three analogs were detected in all strains. Rather, in culture media the detected compounds were variable among strains, two of them being okadaic acid analogs not found on cell extracts. As a result, the taxonomy of the species was revised and P. maculosum is proposed as a junior synonym of P. hoffmannianum whose description is emended.


Assuntos
Dinoflagelados/química , Dinoflagelados/classificação , Toxinas Marinhas/química , Ácido Okadáico/química , Cromatografia Líquida , Dinoflagelados/citologia , Dinoflagelados/genética , Espectrometria de Massas , Filogenia , RNA de Algas/análise , RNA de Protozoário/análise , RNA Ribossômico/análise , Espanha
20.
Harmful Algae ; 78: 95-105, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30196930

RESUMO

Previous studies indicate differences in bloom magnitude and toxicity between regional populations, and more recently, between geographical isolates of Dinophysis acuminata; however, the factors driving differences in toxicity/toxigenicity between regions/strains have not yet been fully elucidated. Here, the roles of prey strains (i.e., geographical isolates) and their associated attributes (i.e., biovolume and nutritional content) were investigated in the context of growth and production of toxins as a possible explanation for regional variation in toxicity of D. acuminata. The mixotrophic dinoflagellate, D. acuminata, isolated from NE North America (MA, U.S.) was offered a matrix of prey lines in a full factorial design, 1 × 2 × 3; one dinoflagellate strain was fed one of two ciliates, Mesodinium rubrum, isolated from coastal regions of Japan or Spain, which were grown on one of three cryptophytes (Teleaulax/Geminigera clade) isolated from Japan, Spain, or the northeastern USA. Additionally, predator: prey ratios were manipulated to explore effects of the prey's total biovolume on Dinophysis growth or toxin production. These studies revealed that the biovolume and nutritional status of the two ciliates, and less so the cryptophytes, impacted the growth, ingestion rate, and maximum biomass of D. acuminata. The predator's consumption of the larger, more nutritious prey resulted in an elevated growth rate, greater biomass, and increased toxin quotas and total toxin per mL of culture. Grazing on the smaller, less nutritious prey, led to fewer cells in the culture but relatively more toxin exuded from the cells on per cell basis. Once the predator: prey ratios were altered so that an equal biovolume of each ciliate was delivered, the effect of ciliate size was lost, suggesting the predator can compensate for reduced nutrition in the smaller prey item by increasing grazing. While significant ciliate-induced effects were observed on growth and toxin metrics, no major shifts in toxin profile or intracellular toxin quotas were observed that could explain the large regional variations observed between geographical populations of this species.


Assuntos
Cilióforos/fisiologia , Dinoflagelados/química , Dinoflagelados/crescimento & desenvolvimento , Cadeia Alimentar , Toxinas Marinhas/química , Cilióforos/crescimento & desenvolvimento , Proliferação Nociva de Algas
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