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Leiodermatium, a sponge of the order Lithistida is the source of the natural product leiodermatolide, a potent antimitotic agent that exhibits nanomolar level cytotoxicity against a variety of human tumor cell lines while showing reduced toxicity to normal cell lines. This natural product is of interest as a potential anticancer agent however the provision of the material required for advanced preclinical and clinical investigation remains an issue.
The microbial population of sponges has been implicated in the production of many of the complex metabolites isolated from sponges. If production can be shown to occur in a microbial system then there is the potential for a relatively inexpensive method to supply the needs of clinical trials and the marketplace.
This project, funded by Florida Sea Grant, is studying the Florida representatives of the genus Leiodermatium which grow in three distinct morphotypes at depths of 200-500m. Of these, only one contains leiodermatolide and in this morphotype the level of production is highly variable ranging from not detectable to 10mg/kg sponge biomass. The unique structural characteristics of leiodermatolide are allowing us to develop molecular probes that can be used to identify microbes with the genetic potential for leiodermatolide production.
While the ultimate goal of this project is to develop a fermentation process for the production of leiodematolide, we are also making significant progress in defining the microbial population of this group of sponges, comparing the sponge-associated population with that of the environment, and developing new microbial cultivation methods.