Cloning a Sea Organism Gene to Treat Cancer

Scientists are cloning the bryA gene found in the marine invertebrate Bugula neritina, which may be the first step in the production of bryostatins, potential anticancer agents.

"To be able to show that this gene really exists has been the Holy Grail for the last 10 years,” observed Prof. Margo Haygood, from the Scripps Institution of Oceanography at the University of California (San Diego, CA, USA). "This takes us beyond just suspecting that a bacteria might be involved to actually having a gene that looks like the right thing.”

Specific marine organisms including B neritina, a brown bryozoan marine animal with thread-like tufts, have a symbiotic relationship with bacteria that acts as a chemical defense mechanism for the host animal. In 2001, Prof. Haygood and coworkers discovered that the bacteria living in this marine animal were the source of bryostatins, a family of chemical agents being closely evaluated for their possible role as anticancer agents.

One of the key hurdles hindering widespread bryostatin production is the lack of a practical and inexpensive functional method of making the compounds. The bacteria cannot be cultured in laboratories, and gathering large numbers of the animals at sea would be environmentally damaging. One way to solve this problem is to clone the genes involved in normal bryostatin development. In the December 2004 issue of Chemistry and Biology, the researchers describe the mechanism by which they cloned a large complex of genes and extracted bryA, a gene for a catalyst active in bryostatin biosynthesis. The gene may synthesize a piece of the pharmacologically active part of bryostatin and thus may be useful in developing clinical beneficial bryostatin byproducts.

"The isolation of bryA represents a significant step forward in understanding bryostatin biosynthesis and eventually harnessing bry genes to produce bryostatins and derivatives inexpensively and in abundant quantities,” wrote the study's authors. The Scripps researchers are now trying to utilize bryA to extract bryostatin compounds.

Most cancer agents act by destroying quickly growing cells, in many instances, interfering with the body's normal processes. Bryostatin appears to work by turning on the mechanism that controls how cells behave in the body. In the instance of leukemia, for example, it appears to normalize the cells and make them behave like healthy blood cells.




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Scripps Institution of Oceanography