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Innovative study finds way to 'bio-synthesize' an anti-cancer compound

In a project that could have far-reaching implications for natural-product drug development, scientists have shown how a microbe that lives inside sea squirts could be used to biosynthesize a chemical compound that may help fight cancer.

The photosynthetic microbe, Prochloron didemni, lives as an endosymbiont inside the sea squirt Lissoclinum patella. So far, scientists have not been able to culture the microbe anywhere else.

Ground-up extracts of that sea squirt have been shown to contain patellamides, small peptides that appear useful in treating some cancers. Until this study, scientists had suspected but had not proven that Prochloron microbes produce patellamides.

The research paper, published online this week in the Proceedings of the National Academy of Sciences (PNAS), demonstrates that Prochloron didemni produces two patellamide compounds (A and C) and pinpoints the gene pathways that are used in that chemical biosynthesis.

"Coral reefs and other ocean environments are like rainforests full of natural chemicals to potentially treat human disease," says Eric W. Schmidt, Ph.D., assistant professor of medicinal chemistry at the University of Utah's College of Pharmacy. "Unfortunately, it's difficult to supply pharmaceuticals from these delicate environments. We have solved this by finding specific genes for the synthesis of chemicals using laboratory bacteria."

Schmidt had isolated and prepared the DNA of the microbe samples collected from sea squirts in the seabed near the Republic of Palau in Micronesia. Jacques Ravel, Ph.D., and other scientists at The Institute for Genomic Research (TIGR) in Rockville, MD, then sequenced the Prochloron genome. Working with Schmidt, they found the chemical pathways in the microbe's gene sequence that are responsible for producing patellamide A and C.

Ravel, who led TIGR's role in the project, says: "For the first time, we have demonstrated the bacterial origin of a natural
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Contact: Phil Sahm
Phil.Sahm@hsc.utah.edu
801-581-2517
University of Utah Health Sciences Center
9-May-2005


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