There’s more than Spanish doubloons in the seas around the Bahamas. A sea-dwelling organism, Salinispora tropica, was found in the marine sediment there in 1991 by
William Fenical and Paul Jensen of the Center for Marine Biotechnology and
Biomedicine at UCSD’s Scripps Institution of Oceanography.
A recent series of discoveries is helping unlock the secrets of this ocean bacterium
that has shown promise in fighting human diseases. The Salinispora derivative "salinosporamide A” is currently in phase I human clinical trials for the treatment of multiple myeloma and other cancers.
First, in June 2007, a research team led by Bradley Moore, a professor at Scripps
and UCSD’s Skaggs School of Pharmacy and Pharmaceutical Sciences and postdoctoral
researcher Daniel Udwary solved the genome of S. tropica. Unlocking the genome is
allowing the researchers to investigate the potential of the organism ’s ability to naturally produce compounds with disease-fighting potential. In the wild, the organism uses such molecules as a chemical defense and for nutrient scavenging.
More recently, Moore and postdoctoral researcher Alessandra Eustáquio, along with their colleagues at the Salk Institute for Biological Studies, discovered an enzyme called SalL inside the organism.
They made a second significant discovery when they turned their attention to how
the organism incorporates chlorine, the key ingredient for triggering Salinispora’s potent cancer-fighting products. After four of the well-established incorporation mechanisms,
or “biological pathways” were tried and rejected, Eustáquio and Moore realized they had just identified a new, fifth biological pathway.
“This was a totally unexpected pathway,” says Moore. “There are well over 2,000
chlorinated natural products and this is the first example in which chlorine is assimilated by this kind of pathway.”
Moore believes the discoveries offer a “road map” that could boost Salinispora’s prospects as a source of disease treatment. Knowing the pathway for how the compounds are produced in nature may help biotechnology scientists manipulate key molecules to
engineer new versions of Salinispora-type drugs.
“It’s possible that drug companies could manufacture this type of drug in greater
quantities now that we know how nature makes it,” says Moore.
— Mario C. Aguilera, ’89 |
