But this chemical defense creates 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 the saponins bind to and pierce. Instead, they have developed two types of cholesterol alternatives: lathosterol and 9(11) sterols, which probably perform the same function of maintaining cell membrane stability. The scientists believe that sea cucumbers’ ability to make 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 shouldn’t be able to poison yourself.”
It turns out that these unique evolutionary possibilities depended on a single 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 superpowers for defending saponin. To find out how the sea cucumbers were genetically different from the rest of the group, Osbourn and Thimmappa (now an assistant professor of genome engineering at Amity University) compared their genomes with those of their echinoderm counterparts. The researchers were particularly interested in studying lanosterol synthase, a highly evolutionarily conserved enzyme crucial for sterol and saponin biosynthesis. It folds their precursor molecules into intricate origami-like shapes.
The team found that sea cucumbers just don’t have it. Instead, they have two enzymes that are of the same family but drastically different in biological function: one gives rise to the saponins found in young sea cucumbers, the other creates their cholesterol alternative and also generates saponins found in their outer walls. One change from the traditional lanosterol synthase sequence in the amino acid chain 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,” Thimmappa says.
This work to characterize and determine the functions of individual chemical compounds in sea cucumbers is “super cool,” said Leah Dann, a PhD student at the University of Queensland who studies island conservation and was not involved in the research. For sea cucumbers, which lack adaptive immunity (the ability to generate antibodies that can prevent future diseases), these saponins may help protect against harmful microbes or fungi. And since they don’t have a spiny outer shell, these chemical defenses may explain why many organisms leave them alone. “They look so delicious,” Dann says. “But most fish won’t touch them.”
“They explained why sea cucumbers contain triterpenoid saponins,” said 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 generate these saponins and special sterols is “very important,” she adds. From this work, Sun is interested in seeing how, in other echinoderm species, the genes associated with saponin biosynthesis may differ 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 nutrition and health,” Osbourn says. “Sea cucumber extracts, which are rich in saponins, are very valuable.” They have long been harvested as a culinary delicacy and revered for their antioxidant and anti-inflammatory health benefits. (The saponin dosage in certain sea cucumbers, while sometimes deadly to fish and other small critters, can be edible and even beneficial to humans.) Studies have previously shown that sea cucumber saponins can lower cholesterol and inhibit inflammation to relieve inflammation. atherosclerotic plaques in mice, and have been associated with anti-tumor activity against cancer.
Saponins also have other home and personal care uses, such as soap making. 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,” 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 sea cucumbers, and to “exploit all the triterpene diversity there is in nature.” Ultimately, she thinks, such molecules could be designed and made on demand, to be used as drugs or marketed as foaming agents or emulsifiers.
In the meantime, though, one of the most likely places to find sea cucumbers and their compounds is in soup — something Osbourn was once served for lunch while attending a conference in China. “It was quite tough,” she says. “I’m sure it was good for me.”