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It sounds like a movie plot – a marine remake of Medicine Man, perhaps – but the source of a molecule with cancer-fighting potential sought for 25 years has finally been found. Better still, the discovery will not lead to an over-harvesting of the soft corals that make it, instead allowing scientists to synthesize it and study it properly.
Coral reefs are so rich with life that competition is fierce. To survive, soft corals need an armory of chemical weapons, and the molecules they make represent an ongoing source of inspiration for medical researchers seeking the next big antibiotic or pain-killer drug.
In the 1990s, biochemical prospectors found a compound they called eleutherobin in samples collected from the Great Barrier Reef. Subsequent research showed the way eleutherobin breaks down cell scaffolding disrupts cancer growth, but further studies couldn't explain how it was made.
Now, a paper in Nature Chemical Biology reveals the gene cluster soft corals use to produce eleutherobin. An accompanying paper from a separate team provides evidence other diterpenes – a suite of molecules to which eleutherobin belongs – also come from soft corals.
“This is the first time we have been able to do this with any drug lead on Earth,” said Professor Eric Schmidt of the University of Utah in a statement.
Although the presence of eleutherobin in soft corals was established decades ago, no one could identify the genes for making it. Indeed, there was debate whether the corals were making the eleutherobin themselves, or getting it from the symbiotic dinoflagellates that give corals their color and sugars.
Harvesting corals on the scale required for clinical quantities of eleutherobin was out of the question – there wasn't even enough for researchers to test whether this really is a likely life-saver or another dead end.
Such is eleutherobin's potential that Schmidt put Drs Paul Scesa and Zhenjian Lin on the case of finding where the soft corals get it from. The fact sea pens – coral relatives that lack symbiotic dinoflagellates – contain molecules very similar to eleutherobin convinced the team the corals were making it themselves, rather than getting it from symbionts.
The authors then searched the genomes of Erythropodium caribaeorum that Scesa brought back from near his Florida birthplace, seeking gene sequences resembling those known to produce molecules resembling eleutherobin. They then transferred promising gene clusters into bacteria to see how this changed what they produced.
The search succeeded, marking the first proof of biosynthetic genes clustered together in animals, as occurs in other organisms. The team also demonstrated the capacity to synthesize eleutherobin in the lab using E. coli modified with the appropriate gene cluster.
The genes to make precursors of eleutherobin and cembrene, a molecule similarly used to repel predators, exist in all soft corals the authors sampled. They believe the capacity to produce these defensive molecules probably dates back to the evolutionary split between hard and soft corals, making soft corals' survival possible.
So many molecules with medical potential have been found in nature that there are currently nowhere near enough researchers employed to investigate them all. It's a near certainty that compounds capable of saving millions sit unstudied in archives because laboratories lack funding to prove their value.
Soft corals' products are considered particularly promising because they have evolved to be effective when digested by predators. This means they can usually be taken orally by humans, rather than needing to be injected, and are also usually easier to study once identified.
“These compounds are harder to find but they’re easier to make in the lab and easier to take as medicine,” Schmidt said.
With coral reefs among the ecosystems most vulnerable to climate change – also threatened by ocean acidification, local pollution, and overfishing – opportunities to study this cornucopia are disappearing fast. We may have found eleutherobin in time, but countless other molecules of potential value are slipping through our fingers.
