Date of Completion

Spring 5-1-2016

Thesis Advisor(s)

Marcy J. Balunas; Spencer V. Nyholm

Honors Major

Molecular and Cell Biology


Medicinal and Pharmaceutical Chemistry | Pharmacy and Pharmaceutical Sciences


Marine natural product drug discovery has begun to play an important role in the treatment of diseases. Early drug discovery from natural products came primarily from plants, but after the discovery and development of penicillin, scientists started looking at natural products from microorganisms. Numerous natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity in the production of biologically active secondary metabolites. Ascidians, also known as tunicates, are marine invertebrates that contain many host-associated microbes. Adult tunicates are sessile, which makes them vulnerable to predators, and thus, they are hypothesized to use host-associated bacteria and their secondary metabolites for chemical defense. Many secondary metabolites cannot be produced under laboratory conditions because growth conditions in a flask culture differ from conditions of the natural environment. One method, mixed fermentation, has been show to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity of co-cultured extracts. A Streptomyces sp. from a Panamanian tunicate was isolated and subsequently co-cultured with challenge organisms Bacillus subtilis, methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa and extracted. The minimum inhibitory concentration of the extracts and the LC-MS profiles show upregulation of the challenge extracts, particularly the Streptomyces sp. co-cultured with MRSA. The competitive interactions of co-cultures may enhance metabolite production and further our understanding of microbial interactions.