Маитотоксин: Өте күшті биоуғы және оның құрылымы туралы даулар

Chemical compound

Maitotoxin (MTX) is an extremely potent biotoxin produced by Gambierdiscus toxicus, a dinoflagellate species. Maitotoxin has been shown to be more than one hundred thousand times as potent as VX nerve agent. Maitotoxin is so potent that it has been demonstrated that an intraperitoneal injection of 130 ng/kg was lethal in mice. 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 the dinoflagellate Gambierdiscus toxicus.

Maitotoxin activates extracellular calcium channels, leading to an increase in levels of cytosolic Ca2+ ions. The exact molecular target of maitotoxin is unknown, but it has been suggested that maitotoxin binds to the plasma membrane Ca2+ ATPase (PMCA) and turns it into an ion channel, similar to how palytoxin turns the Na+/K+ ATPase into an ion channel. Ultimately, a necroptosis cascade is activated, resulting in membrane blebbing and eventually cell lysis. Maitotoxin can indirectly activate calcium binding proteases calpain 1 and calpain 2, contributing to necrosis. The toxicity of maitotoxin in mice is the highest for nonprotein toxins: the LD50 is 50 ng/kg.

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 methyl groups, 28 hydroxyl groups, and 2 sulfuric acid esters and has an amphipathic structure. Its structure was established through analysis using nuclear magnetic resonance at Tohoku University, Harvard University and the University of Tokyo in combination with mass spectrometry, and synthetic chemical methods. However, Andrew Gallimore and Jonathan Spencer have 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. K. C. Nicolaou and Michael Frederick argue that despite this biosynthetic argument, the originally proposed structure could still be correct. The controversy has yet to be resolved.

The molecule is produced in nature via a polyketide synthase pathway. although as of 2015 the project is on hold due to lack of funding.