Health

One of the biggest “biosynthetic” puzzles of the last century, solved: we have managed to synthesize the puffer fish toxin in a simple way

The operation is delicate. The liver and ovaries must be removed with great care and the skin, in order not to contaminate the rest of the animal’s meat, must be removed in a very specific way, developed over 2,300 years ago. For this reason, not everyone can do it. Only after three full years dedicated to study and a very complex exam that includes theoretical tests, but also consuming the result of your own work, a cook can prepare the most toxic fish in the world.

We have now learned how to easily synthesize that poison. Something that will be key to the new generation of painkillers.

the fugu. The fugu, known among us as ‘puffer fish’, is considered a delicacy in Japan and the United States; In Europe, regardless of its consideration, its consumption is prohibited and it is for a good reason: it is a tremendously toxic animal, the second most poisonous vertebrate species in the world (after the poisonous golden frog). The explanation is simple (and, at the same time, tremendously complicated): tetrodotoxin.

One of the most dangerous toxins in the world. Tetrodotoxin is one of the most potent neurotoxins known. Traditionally, it was believed to be something specific to puffer fish. However, in recent years, it has been found in a wide variety of species: from octopuses to toads and newts. This is how we discovered that it was not something that those animals produced.

It was something biosynthesized by certain bacteria that infect these species; something that accumulates in the bodies of its hosts and, finally, by one of those evolutionary tricks, has a key role in defending them against predators.

beyond the fish. What’s interesting about this is that the toxin has many uses beyond fish. It has been tested as a treatment for diseases such as cancer or migraines and, in recent years, has been studied very carefully to learn about the biosynthesis and ecology of the next generation of painkillers.

Focusing on its current practical uses, tetrodotoxin has become an indispensable tool in neurological research because it selectively blocks sodium channels and can therefore be used to silence electrical signals within specific neuronal circuits.

A biosynthetic puzzle. The problem is that the tetrodotoxin molecule has an intricate structure of interconnected oxygen-rich rings that, frankly, has been a huge challenge to synthesize. The first time it was achieved was in 1972, but the method to achieve it was so complex that it was not worth doing. Now researchers led by David Konrad have found a relatively simple way to synthesize the toxin from a glucose derivative.

We are not talking about a revolution, it is true. It is a 22-step process that allows an overall yield of 11% from the starting materials. However, it is a giant step in our ability to understand and produce some of the most complex molecules in nature. One step will open new paths to modern medicine.

Image | Brian Yurasits

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