FSU chemists use sea sponge bacteria to create new molecules for drug discovery

Florida State University chemists have synthesized new molecules derived from bacteria found in a Pacific Ocean sea sponge, a breakthrough for the future of drug development, particularly for rare forms of cancer.

“Around 50 percent of approved drugs are either natural products or derivatives of natural products,” said Zackary Firestone, a fourth-year doctoral student in FSU’s Department of Chemistry and Biochemistry, and the study’s lead author. “Synthetic access to these molecules is important because it allows for easier procurement for biological testing as well as the making of new derivatives.”

The research team is the first to successfully synthesize two new marine natural products: tetradehydrohalicyclamine B and epi-tetradehydrohalicyclamine B. Both were isolated from bacteria that lives in symbiosis with Acanthostrongylophora ingens, a Pacific-dwelling sea sponge.

Sea sponges and their cohabitant bacteria are an important source of biologically active molecules. The chemists who realize these natural marine products’ potential through chemical synthesis play a foundational role in evaluating their merit as new medicinal leads for various diseases. The findings were published earlier this year in the Journal of the American Chemical Society, ACS’ flagship scholarly journal.

How it works

Discovered in 2018, tetradehydrohalicyclamine B can inhibit proteasomes, large, barrel-shaped protein complexes that perform waste-management activities within cells by disposing of damaged proteins.

Some rare cancers, like multiple myeloma and mantle cell lymphoma, produce an abundance of toxic proteins, meaning the cancer’s survival and spread rates are heavily dependent on the cancer cell’s ability to dispose of this additional waste. Proteasome inhibitors are an important form of cancer therapy: They enable a buildup of toxic proteins, which places cancer cells under so much stress that they die off, slowing or stopping the spread in its tracks.

Epi-tetradehydrohalicyclamine B, discovered in 2019, hasn’t yet been the subject of published biological study. However, due to its unique structure, the molecule has attracted considerable attention among organic synthetic chemists for its pharmaceutical potential.

Both molecules are derived from bacteria growing in Acanthostrongylophora ingens, a sea sponge primarily found off the coast of Indonesia. As the source for a variety of bioactive molecules, the sponge is in high global demand by researchers. These samples are individually collected by trained scuba divers and often frozen immediately to prevent chemical degradation before shipment. Laboratory synthesis of key molecules within the sponge will expand research activity without limits instilled by natural sea sponge populations.

“These complex molecules have shown promise in medicinal applications, but gathering large quantities of them is difficult and expensive,” Firestone said. “We make these molecules from materials you can buy from suppliers, giving researchers easier access to the molecules as well as the ability to modify them to improve their properties.”