Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species
Identifying compounds responsible for the observed toxicity of the <i>Gambierdiscus</i> species is a critical step to ascertaining whether they contribute to ciguatera poisoning. Macroalgae samples were collected during research expeditions to Rarotonga (Cook Islands) and North Meyer Isl...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/7/453 |
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| author | J. Sam Murray Sarah C. Finch Elizabeth M. Mudge Alistair L. Wilkins Jonathan Puddick D. Tim Harwood Lesley L. Rhodes Roel van Ginkel Frode Rise Michèle R. Prinsep |
| author_facet | J. Sam Murray Sarah C. Finch Elizabeth M. Mudge Alistair L. Wilkins Jonathan Puddick D. Tim Harwood Lesley L. Rhodes Roel van Ginkel Frode Rise Michèle R. Prinsep |
| author_sort | J. Sam Murray |
| collection | DOAJ |
| description | Identifying compounds responsible for the observed toxicity of the <i>Gambierdiscus</i> species is a critical step to ascertaining whether they contribute to ciguatera poisoning. Macroalgae samples were collected during research expeditions to Rarotonga (Cook Islands) and North Meyer Island (Kermadec Islands), from which two new <i>Gambierdiscus</i> species were characterized, <i>G. cheloniae</i> CAWD232 and <i>G. honu</i> CAWD242. Previous chemical and toxicological investigations of these species demonstrated that they did not produce the routinely monitored Pacific ciguatoxins nor maitotoxin-1 (MTX-1), yet were highly toxic to mice via intraperitoneal (i.p.) injection. Bioassay-guided fractionation of methanolic extracts, incorporating wet chemistry and chromatographic techniques, was used to isolate two new MTX analogs; MTX-6 from <i>G. cheloniae</i> CAWD232 and MTX-7 from <i>G. honu</i> CAWD242. Structural characterization of the new MTX analogs used a combination of analytical chemistry techniques, including LC–MS, LC–MS/MS, HR–MS, oxidative cleavage and reduction, and NMR spectroscopy. A substantial portion of the MTX-7 structure was elucidated, and (to a lesser extent) that of MTX-6. Key differences from MTX-1 included monosulfation, additional hydroxyl groups, an extra double bond, and in the case of MTX-7, an additional methyl group. To date, this is the most extensive structural characterization performed on an MTX analog since the complete structure of MTX-1 was published in 1993. MTX-7 was extremely toxic to mice via i.p. injection (LD<sub>50</sub> of 0.235 µg/kg), although no toxicity was observed at the highest dose rate via oral administration (155.8 µg/kg). Future research is required to investigate the bioaccumulation and likely biotransformation of the MTX analogs in the marine food web. |
| first_indexed | 2024-03-09T13:28:54Z |
| format | Article |
| id | doaj.art-176f02129dee4652b1c61911507fbb51 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T13:28:54Z |
| publishDate | 2022-07-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-176f02129dee4652b1c61911507fbb512023-11-30T21:20:21ZengMDPI AGMarine Drugs1660-33972022-07-0120745310.3390/md20070453Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> SpeciesJ. Sam Murray0Sarah C. Finch1Elizabeth M. Mudge2Alistair L. Wilkins3Jonathan Puddick4D. Tim Harwood5Lesley L. Rhodes6Roel van Ginkel7Frode Rise8Michèle R. Prinsep9Cawthron Institute, Private Bag 2, Nelson 7040, New ZealandAgResearch, Ruakura Research Centre, Private Bag 3123, Hamilton 3240, New ZealandBiotoxin Metrology, National Research Council Canada, 1411 Oxford Street, Halifax, NS B3H 3Z1, CanadaSchool of Science, University of Waikato, Private Bag 3105, Hamilton 3240, New ZealandCawthron Institute, Private Bag 2, Nelson 7040, New ZealandCawthron Institute, Private Bag 2, Nelson 7040, New ZealandCawthron Institute, Private Bag 2, Nelson 7040, New ZealandCawthron Institute, Private Bag 2, Nelson 7040, New ZealandDepartment of Chemistry, University of Oslo, Blindern, P.O. Box 1033, NO-0315 Oslo, NorwaySchool of Science, University of Waikato, Private Bag 3105, Hamilton 3240, New ZealandIdentifying compounds responsible for the observed toxicity of the <i>Gambierdiscus</i> species is a critical step to ascertaining whether they contribute to ciguatera poisoning. Macroalgae samples were collected during research expeditions to Rarotonga (Cook Islands) and North Meyer Island (Kermadec Islands), from which two new <i>Gambierdiscus</i> species were characterized, <i>G. cheloniae</i> CAWD232 and <i>G. honu</i> CAWD242. Previous chemical and toxicological investigations of these species demonstrated that they did not produce the routinely monitored Pacific ciguatoxins nor maitotoxin-1 (MTX-1), yet were highly toxic to mice via intraperitoneal (i.p.) injection. Bioassay-guided fractionation of methanolic extracts, incorporating wet chemistry and chromatographic techniques, was used to isolate two new MTX analogs; MTX-6 from <i>G. cheloniae</i> CAWD232 and MTX-7 from <i>G. honu</i> CAWD242. Structural characterization of the new MTX analogs used a combination of analytical chemistry techniques, including LC–MS, LC–MS/MS, HR–MS, oxidative cleavage and reduction, and NMR spectroscopy. A substantial portion of the MTX-7 structure was elucidated, and (to a lesser extent) that of MTX-6. Key differences from MTX-1 included monosulfation, additional hydroxyl groups, an extra double bond, and in the case of MTX-7, an additional methyl group. To date, this is the most extensive structural characterization performed on an MTX analog since the complete structure of MTX-1 was published in 1993. MTX-7 was extremely toxic to mice via i.p. injection (LD<sub>50</sub> of 0.235 µg/kg), although no toxicity was observed at the highest dose rate via oral administration (155.8 µg/kg). Future research is required to investigate the bioaccumulation and likely biotransformation of the MTX analogs in the marine food web.https://www.mdpi.com/1660-3397/20/7/453ciguatera poisoningmass spectrometrynuclear magnetic resonance spectroscopydinoflagellatebenthicbioassay |
| spellingShingle | J. Sam Murray Sarah C. Finch Elizabeth M. Mudge Alistair L. Wilkins Jonathan Puddick D. Tim Harwood Lesley L. Rhodes Roel van Ginkel Frode Rise Michèle R. Prinsep Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species Marine Drugs ciguatera poisoning mass spectrometry nuclear magnetic resonance spectroscopy dinoflagellate benthic bioassay |
| title | Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species |
| title_full | Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species |
| title_fullStr | Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species |
| title_full_unstemmed | Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species |
| title_short | Structural Characterization of Maitotoxins Produced by Toxic <i>Gambierdiscus</i> Species |
| title_sort | structural characterization of maitotoxins produced by toxic i gambierdiscus i species |
| topic | ciguatera poisoning mass spectrometry nuclear magnetic resonance spectroscopy dinoflagellate benthic bioassay |
| url | https://www.mdpi.com/1660-3397/20/7/453 |
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