Soft corals produce diterpenoids, chemicals that could be used to treat human disease. Now, scientists have identified the genes that make these important chemicals, opening the door to creating a limitless supply that can be used to produce and test new drugs.
Soft corals are just what their name suggests: they have bodies that move and flow with the ocean’s currents, unlike their more well-known, reef-forming, rigid cousins. They also, like so many plants and animals, produce chemicals that have the potential to fight human disease.
A new study led by scientists at UC San Diego’s Scripps Institution of Oceanography has advanced the science around these health-aiding chemicals, called diterpenoids, by isolating the genes responsible for producing them.
“Coral produce unique chemical compounds not seen in the terrestrial world, so there is lots of excitement to study their biomedical potential,” said corresponding author Bradley Moore, PhD, a marine chemist who is the director of the Center for Marine Biotechnology and Biomedicine and a professor at UC San Diego’s School of Pharmacy and Pharmaceutical Sciences. “Unfortunately, it is super challenging to get enough supply directly from nature. With the genetic blueprint for producing these chemicals now in hand, the door is open to solve the supply issue and discover new compounds that could benefit humankind.”
Plant diterpenoids are known to have diverse biological activities, including anti-cancer, anti-inflammatory, and cardiovascular effects. The most famous example of a plant diterpenoid-derived medicine is the chemotherapy drug paclitaxel (Taxol). However, diterpenoids from soft corals, or octocorals, which are animals, are less researched, but it seems they are about to have their day in the sun.
It started with the discovery, in 2022, that a species of octocoral called the sea pansy (Renilla muelleri) produced diterpenoids and appeared to do that using genes that were close together in the animal’s genome. Moore was the corresponding author on that study, too. In the present study, the researchers set out to confirm the genetic basis of octocoral diterpenoid production.
“Picking through an organism’s entire genome to find all the genes involved in the production of a particular compound is an incredibly daunting task – especially when we may not even know which genes we’re looking for,” said lead author Natalie Grayson, a PhD candidate at Scripps.
First, the researchers sequenced and assembled the genomes of five species of octocoral, identifying a common set of five clustered genes that looked to be involved in producing diterpenoids. Inserting the genes into yeast and bacteria and then analyzing the chemicals they produced, the researchers confirmed what they’d suspected.
“Finding these gene clusters gives us as scientists all the knowledge we need to synthesize these chemicals and makes discovering new drugs or products practical,” Moore said. “This can finally address the supply issue that’s held back exploration of coral biochemistry.”
That “supply issue” is the slow-growing, uncommon nature of octocorals and the fact that they produce only minute amounts of diterpenoids. Also, ripping up a lot of soft coral to extract their diterpenoids on the off chance that they’ll be developed into a therapeutic agent is a bit environmentally unethical. So, the door to development is well and truly open now that they have the means to produce these chemicals in the lab.
“Nature is the best chemist,” said Grayson. “We are only so creative, and we need a healthy ocean if we want to keep discovering this kind of novel chemistry that has evolved over millions and billions of years.”
The study was published in the journal Nature Chemical Biology.
