A new study uncovers the genetic blueprint for coral chemicals with anti-cancer and anti-inflammatory properties.
A new study led by scientists at UC San Diego’s Scripps Institution of Oceanography may finally unlock soft corals’ chemical potential, empowering researchers to study the chemicals in depth.
The chemicals, called diterpenoids, have shown promise in fighting cancer and reducing inflammation but are produced in tiny amounts by slow-growing and uncommon corals, making it environmentally destructive and impractical to supply enough of the compounds to test or produce new drugs.
The study, published June 13 in Nature Chemical Biology and supported by grants from the National Institutes of Health, the National Science Foundation and NOAA, found a cluster of five genes responsible for the production of diterpenoids across multiple species of a type of coral called octocorals.
Discovering this gene cluster enables biochemists to produce the octocoral compounds in the lab and investigate their potential as medicines or other products.
“Corals produce unique chemical compounds not seen in the terrestrial world, so there is lots of excitement to study their biomedical potential,” Bradley Moore, the study’s senior author and a marine chemist with joint appointments at SIO, where he is the director of the Center for Marine Biotechnology and Biomedicine, and UCSD’s Skaggs School of Pharmacy and Pharmaceutical Sciences, said in a press release.
“The door is open to solve the supply issue and discover new compounds that could benefit humankind.”
Octocorals are an ancient group of animals that includes soft corals and sea pens. Compared to their reef-forming cousins, octocorals are soft-bodied, lacking the physical defense of a hard skeleton. To avoid being eaten, scientists believe octocorals use chemical defenses that include diterpenoids, which are also widely used by plants to ward off herbivores and for a variety of other biological functions.
Plant diterpenoids have been the basis of numerous important medicines such as the anti-cancer drug taxol, which comes from the Pacific yew tree and has been administered to millions of patients to slow tumor growth.
Octocoral diterpenoids have shown anti-cancer and anti-inflammatory properties as well, but have chemical structures unlike anything seen on land.
Until this study, scientists knew very little about octocorals’ genetic makeup.
Natalie Grayson, a PhD candidate in the Moore Lab at UC San Diego’s Scripps Institution of Oceanography, works in the lab to unlock the biomedical potential of soft corals.
Erik Jepsen, SIO UCSD
“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 Natalie Grayson, a PhD candidate at Scripps and first author of the study.
Finding all the genes an organism uses to code for the production of a given chemical matters as it allows researchers to insert those genes into microbes such as yeasts, which serve as living chemical factories to produce larger quantities of the chemical in the lab. If those genes are clustered together, finding them is much easier.
In the study, the researchers set out to prove that octocorals cluster the genes related to diterpenoid production. The team started by sequencing and assembling the genomes of five octocoral species. By exploring those five genomes as well as those of three other species that were publicly available, the researchers were able to identify a common set of five genes clustered together that appeared to be involved in diterpenoid production.
To test whether this gene cluster was actually related to making the compounds, the researchers inserted the genes into yeast and bacteria and then analyzed the chemicals the microbes produced. The results confirmed that the clustered genes were indeed the genetic assembly line for these unique chemicals.
“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,” said Moore.
“This can finally address the supply issue that’s held back exploration of coral biochemistry.”
Next, Moore’s lab plans to insert the gene clusters they discovered in these octocorals into microbes to produce larger quantities of the diterpenoids for further study. This ability to synthesize the compounds in the lab also allows researchers mining marine biochemistry to tread more lightly on the planet by requiring fewer samples from the deep.
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