Key trigger for potent cancer-fighting marine product identified
London, January 5: Scientists at Scripps Institution of Oceanography have made a significant discovery in their marine biomedical laboratories by uncovering a key trigger for a potent cancer-fighting marine product, currently being tested to treat cancer in humans.
The researchers say that their findings may pave the way for new applications of the natural product in treating human diseases.
Lead researcher Bradley Moore, a professor at the Skaggs School of Pharmacy and Pharmaceutical Sciences and Scripps Institute of Oceanography, has revealed that his team has discovered an enzyme called SalL inside Salinispora tropica, a promising marine bacterium identified in 1991 by Scripps researchers.
The researcher, who carried out this study working with postdoctoral researcher Alessandra Eustaquio and with their colleagues at The Salk Institute for Biological Studies, said that his team had also identified a novel process by which the marine bacterium incorporates a chlorine atom, a key ingredient for triggering its potent cancer-fighting natural product.
While previously known methods for activating chlorine were processed through oxygen-based approaches, the new method employs a substitution strategy that uses non-oxidized chlorine as it is found in nature.
"This was a totally unexpected pathway. 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," Nature Chemical Biology quoted Moore as saying.
The Salinispora derivative "salinosporamide A" is currently in phase I human clinical trials for the treatment of multiple myeloma and other cancers. Moore and his colleagues solved the genome of Salinispora tropica (S. tropica) in June, an achievement that helped pave the way for the new discoveries.
Eustaquio and her colleagues discovered a new enzyme and biological pathway in S. tropica, a promising marine organism that creates a natural product being tested to treat cancer.
Moore feels that such discoveries may help increase S. tropicaâ€™s potential for drug development. He says that the knowledge of how the natural product is made biologically may give scientists the ability to manipulate key molecules to engineer new versions of Salinispora-derived drugs.
He even feels that genetic engineering may allow the development of second-generation compounds that are not found in nature.
"It's possible that drug companies could manufacture this type of drug in greater quantities now that we know how nature makes it," said Moore.
Moore admits that, as of now, his team is unclear about how pervasively SalL and its unique biological activation pathway exist in the ocean environment. He, however, says that chlorine is a major component of seawater, and a fundamental component of Salinispora's disease-inhibiting abilities.
He corroborates his statement by pointing out that this is the reason why salinosporamide A is 500 times more potent than its chlorine-free analog salinosporamide B.
"The chlorine atom in salinosporamide A is key to the drug's irreversible binding to its biological target and one of the reasons the drug is so effective against cancer," said Moore.
Eustaquio believes that findings the enzyme and its new pathway may carry implications for understanding evolutionary developmentsâ€”such as clues for how and why related enzymes are activated in different ways. (ANI)