Many marine invertebrates produce natural products that resemble compounds previously isolated from bacteria.  This has prompted scientists to investigate whether marine bacteria that inhabit invertebrates might also be able to produce these natural products.  For example, the enediynes namenamicin and shishijimicins A to C1 were isolated from the tunicates Polysynchraton lithostrotum and Didemnum proliferum Kott, respectively, yet all other known enediynes are produced by terrestrial actinomycetes.  Thus, it may be possible that these potent anticancer compounds are actually produced by the marine microorganisms inhabiting these tunicates.  To investigate this theory, actinomycetes were isolated from tissue samples of D. proliferum, fermented in several fermentation media, and the fermentation extracts were tested in the biochemical induction assay (BIA).  The majority (62%) of the fermentation extracts induced in the BIA indicating that the strains produce DNA-damaging compounds.  In addition, primers were developed to PCR amplify four different genes, unbL, unbU, unbV, and pksE, common only to enediyne biosynthetic pathways.  We were able to detect two or more of these genes from the genomic DNA of three taxonomic groups of actinomycetes, Salinispora arenicola, “Salinispora pacfica”, and Micromonospora chalcea suggesting that they possess the biosynthetic capacity to produce enediynes.  Based on these results, further studies were performed with one strain from each taxonomic group.  A combination of media improvement, UV mutagenesis and fermentation with synthetic polymeric resins or solid support was used to improve the yield and detection of cytotoxic compounds.