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Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species

Identifying compounds responsible for the observed toxicity of the Gambierdiscus 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 Islan...

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Autores principales: Murray, J. Sam, Finch, Sarah C., Mudge, Elizabeth M., Wilkins, Alistair L., Puddick, Jonathan, Harwood, D. Tim, Rhodes, Lesley L., van Ginkel, Roel, Rise, Frode, Prinsep, Michèle R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324523/
https://www.ncbi.nlm.nih.gov/pubmed/35877746
http://dx.doi.org/10.3390/md20070453
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author Murray, J. Sam
Finch, Sarah C.
Mudge, Elizabeth M.
Wilkins, Alistair L.
Puddick, Jonathan
Harwood, D. Tim
Rhodes, Lesley L.
van Ginkel, Roel
Rise, Frode
Prinsep, Michèle R.
author_facet Murray, J. Sam
Finch, Sarah C.
Mudge, Elizabeth M.
Wilkins, Alistair L.
Puddick, Jonathan
Harwood, D. Tim
Rhodes, Lesley L.
van Ginkel, Roel
Rise, Frode
Prinsep, Michèle R.
author_sort Murray, J. Sam
collection PubMed
description Identifying compounds responsible for the observed toxicity of the Gambierdiscus 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 Gambierdiscus species were characterized, G. cheloniae CAWD232 and G. honu 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 G. cheloniae CAWD232 and MTX-7 from G. honu 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(50) 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.
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spelling pubmed-93245232022-07-27 Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species Murray, J. Sam Finch, Sarah C. Mudge, Elizabeth M. Wilkins, Alistair L. Puddick, Jonathan Harwood, D. Tim Rhodes, Lesley L. van Ginkel, Roel Rise, Frode Prinsep, Michèle R. Mar Drugs Article Identifying compounds responsible for the observed toxicity of the Gambierdiscus 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 Gambierdiscus species were characterized, G. cheloniae CAWD232 and G. honu 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 G. cheloniae CAWD232 and MTX-7 from G. honu 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(50) 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. MDPI 2022-07-12 /pmc/articles/PMC9324523/ /pubmed/35877746 http://dx.doi.org/10.3390/md20070453 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Murray, J. Sam
Finch, Sarah C.
Mudge, Elizabeth M.
Wilkins, Alistair L.
Puddick, Jonathan
Harwood, D. Tim
Rhodes, Lesley L.
van Ginkel, Roel
Rise, Frode
Prinsep, Michèle R.
Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species
title Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species
title_full Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species
title_fullStr Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species
title_full_unstemmed Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species
title_short Structural Characterization of Maitotoxins Produced by Toxic Gambierdiscus Species
title_sort structural characterization of maitotoxins produced by toxic gambierdiscus species
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9324523/
https://www.ncbi.nlm.nih.gov/pubmed/35877746
http://dx.doi.org/10.3390/md20070453
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