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

But this chemical defense creates a big problem for sea cucumbers: they have to avoid being killed by their own toxins. And this means that their own cells cannot contain cholesterol, the target that saponins bind to and penetrate. Instead, they developed two types of cholesterol alternatives: lathosterol and 9(11) sterols, which presumably fulfill the same function of maintaining cell membrane stability. Scientists believe that sea cucumbers’ ability to produce saponins—and these saponin-resistant sterols—evolved simultaneously. “We think it’s a self-defense strategy,” Osbourn says. “If you can produce these toxic compounds, you must be able to not poison yourself.”

As it turns out, these unique evolutionary abilities depended on one point. Sea cucumbers are part of the echinoderm family, along with starfish and sea urchins. They all share a common ancestor, but sea urchins don’t have the same defensive superpowers of saponins. To figure out how sea cucumbers diverged genetically 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, the researchers were interested in studying lanosterol synthase, a highly evolutionarily conserved enzyme that is critical for the biosynthesis of sterols and saponins. It folds their precursor molecules into intricate origami-like shapes.

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

This work of characterizing and determining 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 associated with the study. For sea cucumbers, which do not have adaptive immunity (the ability to make antibodies that can prevent future diseases), these saponins can help protect against harmful microbes or fungi. And since they don’t have a spiny outer shell, this chemical defense may explain why many organisms leave them alone. “They look so delicious,” says Dann. “But most fish won’t touch them.”

“They explained why sea cucumbers have triterpenoid saponins,” says Lina Sun, a professor at the Institute of Oceanology of the Chinese Academy of Sciences. (Sun is not affiliated with the study, and her comments were translated from Chinese.) Discovering and characterizing the two synthase pathways that create these saponins and special sterols is “very important,” she adds. From this work, Sun is interested to see how in other species of echinoderms, genes related to saponin biosynthesis might differ from those in sea cucumbers.

A compound that attacks cholesterol has some intriguing implications for human health. “Sea cucumbers are highly valued for both food and health,” says Osbourn. “Sea cucumber extracts, which are rich in saponin, are very valuable.” They have long been harvested as a culinary delicacy – and prized for their antioxidant and anti-inflammatory health benefits. (The dose of saponins in certain sea cucumbers, while sometimes lethal to fish and other small creatures, can be edible and even beneficial to humans.) Research has previously found that sea cucumber saponins can lower cholesterol and inhibit inflammation to help alleviate atherosclerotic plaques. in mice, and are associated with antitumor activity against cancer.

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

In the future, she and her team are interested in learning how to synthesize more of these naturally occurring compounds—to recreate them on a larger scale without having to harm the sea cucumbers, and to “use all the diversity of triterpenes that exist in nature.” Ultimately, she believes, such molecules could be designed and made on demand, to be used as drugs or commercialized as foaming agents or emulsifiers.

In the meantime, though, one of the most likely places you’ll find sea cucumbers and their compounds is in soup—something Osbourn once served for lunch when he attended a conference in China. “It was quite chewy,” she says. “I’m sure it was good for me.”

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