But this chemical defense creates a big problem for sea cucumbers: They must avoid killing themselves with their own toxins. And this means that their own cells cannot contain cholesterol, the target to which the saponins bind and pierce. Instead, they have developed two kinds of cholesterol alternatives: latosterol and 9 (11) sterols, which are likely to fulfill the same function of maintaining cell membrane stability. The researchers believe that the ability of sea cucumbers to make saponins – and these saponin-resistant sterols – developed in parallel. “We think it’s a self-defense strategy,” Osbourn said. “If you can produce these toxic compounds, you need to be able to not poison yourself.”
As it turns out, these unique evolutionary properties depended on a single point. Sea cucumbers are part of the echinoderm family along with starfish and sea urchins. They all have a common ancestor, but sea urchins do not have the same saponin defense superpowers. So to find out how the cucumbers were genetically different from the rest of the group, Osbourn and Thimmappa (now assistant professor of genome engineering at Amity University) compared their genomes with their counterparts in echinoderms. Specifically, the researchers were interested in studying lanosterol synthase, a highly evolutionarily conserved enzyme that is essential for 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 are from the same family but that are drastically different in biological function: One gives rise to the saponins found in young cucumbers, the other creates their cholesterol alternative and also generates saponins found in their exterior walls. A change from the traditional lanosterol synthase sequence in the amino acid chain was all it took to create these two 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 affiliated with the study. For sea cucumbers that do not have adaptive immunity (the ability to generate antibodies that can prevent future diseases), these saponins can help protect against harmful microbes or fungi. And since they do not have a thorny outer shell, these chemical defenses may explain why many organisms leave them alone. “They look so delicious,” Dann says. “But most fish will not touch them.”
“They explained why sea cucumbers have triterpenoid saponins,” says Lina Sun, a professor at the Department of Oceanology at the Chinese Academy of Sciences. (Sun is not affiliated with the study, and her comments have been translated from Chinese.) Discovering and characterizing the two synthase pathways that generate these saponins and special sterols is “very important,” she adds. From this work, Sun is interested in seeing how the genes associated with saponin biosynthesis in other echinoderm species can differ from those in sea cucumbers.
A compound that attacks cholesterol has some exciting 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.” They have long been harvested as a culinary delicacy – and honored for their antioxidant and anti-inflammatory health benefits. (The saponin dosage in certain cucumbers, while sometimes lethal to fish and other small creatures, can be edible and even beneficial to humans.) Studies have previously found that cucumber saponins can reduce cholesterol and inhibit inflammation to relieve atherosclerotic plaques in mice, and has been associated with anti-tumor activity against cancer.
Saponins also have other uses for home care and personal care, such as for making soap. Originally named after their presence in the roots of the soapwort plant (Saponaria), saponins can be dissolved in water to create 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 derived compounds – to recreate them on a larger scale without harming any sea cucumbers, and to “take advantage of all the triterpendiversity that is out there in nature. ” Ultimately, she believes that such molecules could be designed and manufactured as needed, to be used as medicine or commercialized as foaming agents or emulsifiers.
Meanwhile, one of the most likely places you will find sea cucumbers and their compounds is in soup – something Osbourn was once served for lunch when he attended a conference in China. “It was pretty cool,” she says. “I’m sure it was good for me.”