Eric W. Schmidt, Mohamed S. Donia, John McIntosh, Jaeheon Lee, and Olivier Peraud. Medicinal Chemistry, University of Utah, 30 South 2000 East Rm 201, Salt Lake City, UT 84112
Ascidians are marine animals that contain a diverse array of bioactive small molecules with therapeutic potential. It is likely that many of these compounds are produced by bacteria living symbiotically with their animal hosts, and a wide range of symbiotic bacteria are actually present within ascidian tissues. We have employed a variety of approaches to determine the true source of these natural products, including metagenomics and bacterial cultivation. Here, we will describe our recent advances in the discovery and genetic manipulation of pathways to bioactive small molecules from symbiotic bacteria in ascidians and other marine animals. By examining pathways that are very closely related as well as wholly different pathways, it is possible to discern discrete evolutionary events leading to the small molecule diversity found within ascidians. We are using these observations for pathway discovery and engineering to supply and synthesize bioactive small molecules.