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Drugs from the deep blue

rine natural products are an eclectic mix of chemical types, drawing on all the pathways of metabolism, Molinski said. Some are related to fats and proteins; others include elements such as bromine, sometimes bonded into improbable structures.

"It's a rich, complex and edited chemical library," Molinski said. "They're really fascinating little jewels made by niche creatures."

As well as being largely unexplored, the chemistry of these marine organisms is very different than that of land plants and animals, reflecting both a different environment and millions of years of separate evolution. That should make it harder for microbes to evolve resistance to such drugs, as they are being attacked from a completely different direction.

Molinski, a certified diver, and his graduate students make regular collecting trips to study sites in Micronesia, Western Australia and -- using a seagoing vessel, the R/V Seward Johnson based in Florida -- the Atlantic Ocean around the Bahamas. Warm tropical waters support a wider variety of sponges, making them richer prospecting grounds.

Back in the lab, the scientists put extracts from the animals they have collected through a battery of tests. If they find something with interesting properties, the researchers attempt to isolate and identify the molecule.

The next step is to start from conventional chemistry and make the compound in the lab, then try to find the simplest structure with the same properties. This work can pull in techniques from different areas of chemistry and biochemistry, but the pathways used to make these products naturally are far too complex to reproduce with current genetic engineering techniques, Molinski said.

One of their finds is phorboxazole, made by an Indian Ocean sponge collected by Molinski's team off the coast of Western Australia. Phorboxazole A is a potent toxin that in the laboratory, can inhibit the growth of a wide range of tumor cell types even at ve
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Source:University of California - Davis


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