For 25 years, researchers have been searching for the source of a natural chemical that had shown promise in initial studies for treating cancer. Now, researchers at the University of Utah (U of U) Health report they have found the elusive compound in soft corals. Their findings may pave the way for a potential new cancer therapeutic.

The findings are published in the journal Nature Chemical Biology in a paper titled, “Ancient defensive terpene biosynthetic gene clusters in the soft corals.”

“Diterpenes are major defensive small molecules that enable soft corals to survive without a tough exterior skeleton, and, until now, their biosynthetic origin has remained intractable,” wrote the researchers. “Furthermore, biomedical application of these molecules has been hampered by lack of supply. Here, we identify and characterize coral-encoded terpene cyclase genes that produce the eunicellane precursor of eleutherobin and cembrene, representative precursors for the >2,500 terpenes found in octocorals.”

“This is the first time we have been able to do this with any drug lead on Earth,” explained Eric Schmidt, PhD, professor of medicinal chemistry at U of U Health. He led the study with Paul Scesa, PhD, postdoctoral scientist and first author, and Zhenjian Lin, PhD, assistant research professor.

A second research group led by Bradley Moore, PhD, from Scripps Institution of Oceanography at the University of California, San Diego, independently showed that corals make related molecules.

Scesa discovered the compound in a common species of soft coral living off the Florida coast—just a mile from his brother’s apartment. In the 1990s, marine scientists reported that a rare coral near Australia carried a chemical, eleutherobin, with anticancer properties. The chemical disrupts the cytoskeleton, but laboratory studies showed that the compound was also a potent inhibitor of cancer cell growth.

Paul Scesa, PhD, dives for soft corals off the Florida coast. He studies the potential of soft coral chemicals as drug leads. [Paul Scesa]

In the decades following, scientists searched but could not find the chemical in the quantities needed for drug development.

“It didn’t make sense,” Scesa said. “We knew that corals must make eleutherobin.” After all, he and Schmidt reasoned, some soft coral species don’t have symbiotic organisms and yet their bodies contain the same class of chemicals.

The researchers discovered regions of coral DNA that resembled genetic instructions for similar types of compounds from other species. After programming bacteria grown in the lab to follow coral DNA instructions specific to the soft coral, the microorganisms were able to replicate the first steps of making a potential cancer therapeutic.

This proved that soft corals are the source of eleutherobin. It also demonstrated that it should be possible to manufacture the compound in the lab.

The researchers are now focused on filling in the missing steps of the compound’s recipe and determining the best way to produce large amounts of the potential drug.

“My hope is to one day hand these to a doctor,” said Scesa. “I think of it as going from the bottom of the ocean to bench to bedside.”

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