Soft corals are the first animals found to make complex terpenes

Two research teams have discovered independently that soft corals make a class of molecules called terpenes. Scientists had previously believed that these natural products were made by symbiotic microbes that live in corals. What’s more, the researchers have found that the coral genes responsible for terpene synthesis are closely clustered, which means chemists might be able to use them to make these promising drug candidates in the lab more easily.

Plants and bacteria use terpenes to form toxins, fragrances, and other bioactive compounds. Natural product chemists have found a few cases of simple terpene synthesis in animals, but nothing as intricate as the pharmacopeia isolated from soft corals, says Wilfred van der Donk, a chemist at the University of Illinois Urbana-Champaign who was not involved in the coral research.

High-quality genome data for a broad diversity of soft coral species have become available in recent years. Two groups of chemists, one led by Bradley Moore at the Scripps Institution of Oceanography and another led by Eric Schmidt at the University of Utah, scoured the coral genomes for sequences coding for potential terpene-building enzymes.

Both teams found proteins called terpene cyclases, which transform simple precursors into the ring structures that are crucial for synthesizing more complex terpenes. To confirm that these cyclase enzymes were truly part of the corals’ genomes rather than artifacts of the animals’ symbiotic bacteria, the researchers looked for coral-specific genes in nearby coding regions. They were surprised to find other enzymes that could add functional decorations to the cyclic terpenes (Nat. Chem. Biol. 2022, DOI: 10.1038/s41589-022-01027-1 and 10.1038/s41589-022-01026-2).

Because gene clusters like these are common in bacteria, it’s possible that the terpene-synthesizing genes were once acquired from microbes, the authors say. Yet both teams found terpene synthesis pathways in every soft coral genome analyzed, which suggests that they arose in an ancient progenitor of soft corals, Schmidt says. These squishy, sessile animals may use terpenes as a chemical defense against grazing predators; if they do, he says, it could help explain the divergence of soft corals from their stony relatives. Moore agrees, noting that this evolutionary timeline suggests that soft corals began producing terpenes millions of years before plants. The conveniently clustered genes could make coral terpenes easier to study, he says. Moore hopes scientists will soon have access to a steady supply of potential drug candidates by genetically engineering bacteria such as Escherichia coli to make the natural products.

The groups’ joint discovery is a “huge advance” in both natural product biosynthesis and chemical ecology, says David Christianson, a chemist at the University of Pennsylvania. “It’s a big splash,” he says.

Van der Donk says the “profound” revelation that animals can make complex terpenes sparks new questions about corals’ chemical diversity and about which other animals might be hiding similarly remarkable talents.