ORGN 5 |
| For the past 50 or more years, soil-derived bacteria (in particular the chemically-rich actinomycetes) have provided a major pharmaceutical resource for the discovery of over 120 clinically utilized antibiotics and related bioactive compounds. During this time, a major effort was undertaken to examine virtually every terrestrial habitat, world-wide. The oceans, however, which represent >70% of the Earth's surface, were never seriously considered as a source for chemically-unique bacterial diversity. This is because the prevailing view was that actinomycete bacteria were exclusively terrestrial, because the marine environment is far more difficult to sample, and because little methodology was available to insure the successful cultivation of the unusual organisms from the sea. During the last 3-4 years, we have examined deep ocean environments and undertaken a systematic approach to cultivate and identify “marine actinomycetes”, those uniquely adapted to growth in the sea. Our studies have revealed that taxonomically-unique representatives of all the major actinomycete families can readily be cultured. At least 13 diverse phylotypes, which appear unique at the genus level, have been isolated. In culture, we are now observing the production of a diversity of bioactive and structurally-unique secondary metabolites. One recent study identified Salinosporamide A, a potent proteasome inhibitor from the new genus “Salinispora”, that is scheduled for clinical trials in early 2006 for the treatment of cancer. From another genus, the Marinispora, we have isolated potent antitumor-antibiotics, which are active against drug resistant pathogens and have a high degree of selective cytotoxicity against human melanoma. Aspects of the biological diversity of this new drug resource, and the discovery of new molecules relevant to drug discovery will be the focus of this presentation. |
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Ernest Guenther Award in the Chemistry of Natural Products
8:00 AM-12:00 PM, Sunday, 26 March 2006 Georgia World Congress Center -- Georgia Ballroom 2, Oral
Division of Organic Chemistry |