Sea Bacteria May Offer New Way to Make Cancer Drugs

In a study published November 5, 2006, in the online journal Nature Chemical Biology, researchers from the University of Utah (Salt Lake City, UT, USA) studied symbiotic bacteria that live only in sea squirts and other marine life. These bacteria are responsible for making a variety of chemicals, which accumulate in the tissues of sea squirts and may help to defend them against predators. Many of these compounds have anticancer properties, but harvesting them in quantities for large-scale testing and production has been impractical.

The new technique utilizes genetic pathways in the bacteria to generate the small chemical compounds and to manipulate them to devise new potential anti-cancer agents. The ability to make these chemicals in the laboratory opens numerous possibilities for developing drugs to combat cancer, HIV, and other disorders, according to Eric W. Schmidt, Ph.D., assistant professor of medicinal chemistry at the University of Utah College of Pharmacy and senior investigator on the study.

"This represents a new way of attacking the problem,” Dr. Schmidt said. "We're hoping we can use this to find a way to make natural molecules of compounds through single mutations in DNA.”

To synthesize natural compounds, researchers have conventionally produced them in the lab using labor-intensive techniques. More recently, researchers have started to use genes to produce small molecules within laboratory strains of bacteria. This genetic synthesis method is complex because it is still difficult to understand how changing genes can lead to changes in small drug molecules. "The promise of genes is that you can access the tremendous natural diversity of the world's organisms to find new natural compounds for human health,” Dr. Schmidt said. "You can also use genetic engineering to modify these compounds and invent new drugs to target human diseases.”

Sea squirts live with diverse bacteria that synthesize many small molecules. By studying the natural chemical and genetic diversity found in sea squirts and their symbionts, Dr. Schmidt and his colleagues from several institutions in the United States identified individual mutations responsible for changing from one compound to another. By mimicking this natural process, the investigators synthesized a totally new compound. This development may provide a way to genetically create of large chemical libraries for testing against human diseases. "This proves the concept works,” Dr. Schmidt said. "We can extract bacteria from animals, take DNA from the bacteria, and produce compounds.”

Now that the investigators have shown that compounds can be synthesized from DNA, they want to determine how to produce greater quantities of compounds for testing and drug development. Escherichia coli is a good producer of compounds, but production is not yet practical. For the study, Dr. Schmidt obtained sample bacteria from 46 ascidians in the tropical Pacific Ocean near New Guinea.



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