What humans can learn from the sea cucumber’s venomous arsenal

But this chemical defense poses a major problem for sea cucumbers: they must avoid killing themselves with their own toxins. And that means their own cells can’t contain cholesterol, the target that the saponins bind to and penetrate. Instead, they have developed two types of cholesterol alternatives: lathosterol and 9(11)-sterols, which likely serve the same function of maintaining cell membrane stability. The scientists believe that sea cucumbers’ ability to make saponins — and these saponin-resistant sterols — evolved at the same time. “We think it’s a self-defense strategy,” Osbourn says. “Anyone who can produce these toxic compounds does not have to be able to poison themselves.”

As it turned out, these unique evolutionary abilities depended on a single point. Sea cucumbers belong to the echinoderm family along with starfish and sea urchins. They all share a common ancestor, but sea urchins don’t have the same saponin defense superpowers. To find out how the sea cucumbers were genetically different from the rest of the group, Osbourn and Thimmappa (now an assistant professor of genomic engineering at Amity University) compared their genomes to those of their echinoderm counterparts. In particular, researchers were interested in studying lanosterol synthase, an evolutionarily highly conserved enzyme critical to sterol and saponin biosynthesis. It folds their precursor molecules into intricate origami-like shapes.

The team discovered that sea cucumbers just don’t have it. Instead, they have two enzymes that come from the same family but differ drastically in their biological function: one creates the saponins found in young sea cucumbers, the other creates their cholesterol alternative and also creates saponins found in their outer walls. Changing the traditional lanosterol synthase sequence in the amino acid chain was enough to create these two sea cucumber-specific enzymes with vastly different functions — an evolutionary adaptation that was “simple but very elegant,” says Thimmappa.

This work to characterize and determine the functions of individual chemical compounds in sea cucumbers is “super cool,” says Leah Dann, a PhD student at the University of Queensland who studies island conservation and was not involved in the study. In sea cucumbers that don’t have adaptive immunity (the ability to make antibodies that can prevent future disease), these saponins could help protect against harmful microbes or fungi. And since they don’t have a spiny outer shell, these chemical defenses could explain why many organisms leave them alone. “They look so delicious,” says Dann. “But most fish don’t touch them.”

“They explained why sea cucumbers contain triterpenoid saponins,” says Lina Sun, a professor at the Institute of Oceanology of the Chinese Academy of Sciences. (Sun is not involved in the study, and her comments have been translated from Chinese.) Discovering and characterizing the two synthase pathways that make these saponins and specific sterols is “very important,” she adds. Based on this work, Sun is interested to see how other echinoderm species might have different genes associated with saponin biosynthesis from those in sea cucumbers.

A compound that attacks cholesterol has some intriguing implications for human health care. “Sea cucumbers are highly valued for both food and health,” says Osbourn. “Sea cucumber extracts, which are rich in saponins, are very valuable.” Long harvested as a culinary delicacy, they are revered for their antioxidant and anti-inflammatory health benefits. (While the saponin dosage in certain sea cucumbers is sometimes fatal to fish and other small critters, it can be edible and even beneficial to humans.) Studies have previously found that sea cucumber saponins may lower cholesterol and inhibit inflammation to help prevent atherosclerotic plaques alleviate in mice. and have been associated with anti-tumor activity against cancer.

Saponins also have other household and personal care uses, such as making soap. Originally named for their presence in the roots of the soapwort plant (Saponaria) Saponins can dissolve in water to create a frothy broth. “Nature is so good at making chemicals,” says Osbourn admiringly.

In the future, she and her team are interested in learning how to synthesize more of these naturally derived compounds — to replicate them on a larger scale without having to harm sea cucumbers, and to “use all the diversity of triterpenes that’s out there.” Nature.” Ultimately, she believes, such molecules could be designed and manufactured on demand, to be used as medicines or marketed as propellants or emulsifiers.

In the meantime, though, you’re most likely to find sea cucumbers and their compounds in soups — something Osbourn was once served for lunch while attending a conference in China. “It was pretty tough,” she says. “I’m sure it was good for me.”

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