November 2009

Document Type


Degree Name



Dept. of Science & Engineering


Oregon Health & Science University


Marine natural products attract the attention of scientists from different fields due to their proven clinical importance. Ecteinascidin 743 or Et 743 is one of the compounds known from the colonial ascidian Ecteinascidia turbinata in the Caribbean and Mediterranean (Berrill, 1932) and from Ecteinascidia thurstoni in Thailand (Chavanich et al., 2009) and in the Red Sea Egypt (Gab-Alla, 2008). Et 743 is a cyclic peptide with a potent anti-cancer activity and it is currently in Phase II clinical trials (Rinehart et al., 1990; Jimeno et al., 1999; Ryan et al., 2002; Laverdiere et al., 2003). The chemical structure of Et 743 is similar to other bacterial secondary metabolites. This suggests that these chemical agents are produced from bacteria that are in symbiotic association with these marine invertebrates. There are recent evidences for the presence of persistently associated bacteria in E. turbinata from both the Caribbean (Salomon, 2001; Pérez-Matos et al., 2007) and the Mediterranean Sea (Moss and Green, 2003). A putative bacterium―"Candidatus Endoecteinascidia frumentensis" has been reported to be associated with E. turbinata and it was proposed to be the source of Et 743 (Moss and Green, 2003; Pérez-Matos et al., 2007). This study highlights a general strategy for the identification of different Ecteinascidia spp. using different gene markers. The results showed how conserved are the 18S rRNA gene and coxI gene along these tunicate species, and showed the need of a new nuclear markers in order to further resolve the phylogeny of this keystone group in chordate evolution. While this study does not provide direct evidence of Candidatus E. frumentensis to be the source of Et 743, our results yield useful information on bacteria that are persistently and specifically associated with filter feeders in different tissue samples and may help to elucidate the biological and ecological role of these endosymbionts. The identification of the persistent bacteria associated with different Ecteinascidia spp. collected from different sites in Mediterranean Sea and Atlantic Ocean is novel data. It has never been known that E. frumentensis to exist outside E. turbinata. Our results showed E. frumentensis is present as a persistent bacterium in E. thurstoni and Ecteinascidia. We are hoping that our information can be utilized for the high-throughput culturing, metagenomics, phylogenetic studies and identifying the candidate biosynthetic genes responsible for the Et 743.




Div. of Environmental & Biomolecular Systems


School of Medicine



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