The structure elucidation and
biological activities ofhigh molecular weight algal toxins: maitotoxin,
prymnesins andzooxanthellatoxins
Department of
Chemistry, Graduate School of Science, Osaka University, 1-16
Machikaneyama, Toyonaka, Osaka, Japan
b
Japan Food Research Laboratories, 6-11-10 Nagayama, Tama, Tokyo, Japan
Nat. Prod. Rep., 2000,17, 293-314
DOI: 10.1039/A901979K
.Maitotoxin (or MTX) is an extremely potent toxin produced by Gambierdiscus toxicus, a dinoflagellate species. Maitotoxin is so potent that it has been demonstrated that an intraperitoneal injection of 0.13 µg/kg was lethal in mice.[1] Maitotoxin was named from the ciguateric fish Ctenochaetus striatus—called "maito" in Tahiti—from which maitotoxin was isolated for the first time. It was later shown that maitotoxin is actually produced by Gambierdiscus toxicus.
Mechanism of toxicity
Maitotoxin activates Ca2+ permeable, non-selective cation channels, leading to an increase in levels of cytosolic Ca2+ ions. It is thought that maitotoxin leads to the formation of pores on these ion channels. Ultimately, a cell death cascade is activated, resulting in membrane blebbing and eventually cell lysis.[2] Maitotoxin is known to activate cytosolic calcium-activated proteases calpain-1 and calpain-2, contributing to necrosis.[3] The toxicity of maitotoxin in mice is the highest for nonprotein toxins: the LD50 is 50 ng/kg.Molecular structure
The molecule itself is a system of 32 fused rings. It resembles large fatty acid chains and it is notable because it is one of the largest and most complex non-protein, non-polysaccharide molecules produced by any organism. Maitotoxin includes 32 ether rings, 22 methyls, 28 hydroxyls, and 2 sulfuric acid esters and has an amphipathic structure.[4][5][6] Its structure was established through analysis using nuclear magnetic resonance at Tohoku University, Harvard and the University of Tokyo in combination with mass spectrometry, and synthetic chemical methods. However, Gallimore and Spencer recently questioned the structure of maitotoxin at a single ring-junction (the J-K junction), based purely on biosynthetic considerations and their general model for marine polyether biogenesis.[7] Nicolaou and Frederick on the other hand argue that despite this biosynthetic argument, the originally proposed structure could still be correct. [8] The controversy has yet to be resolved.Biosynthesis
The core synthetic route is via a polyketide synthase pathway.[7]Total synthesis
Since 1996 the Nicolaou research group is involved in an effort to synthesise the molecule via total synthesis [9] [10] [11] [12] although the project is currently on hold due to a lack of funding. [13]References
- Chemistry's toughest total synthesis challenge put on hold by lack of funds Katrina Kramer 15 January 2015 Chemistry World http://www.rsc.org/chemistryworld/2015/01/chemistry-grandest-total-synthesis-challenge-maitotoxin-put-hold-lack-funds
Further reading
- Jones, Maitland (2004). Organic Chemistry, Third Edition. W. W. Norton & Company. ISBN 978-0-393-92408-4.
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| Identifiers | |
|---|---|
59392-53-9  |
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| ChemSpider | 25991548 |
| Jmol-3D images | Image |
| Properties | |
| C164H256O68S2Na2 | |
| Molar mass | 3422 g/mol |
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