Discovery of Biomedically Important Marine Natural Products: Some Effective Paradigms, Lessons Learned, and Significant Outcomes

The marine natural products program begun at UC Santa Cruz (UCSC) in the early 1970's has a rich history and continued promise for future significant discoveries. To date, more than 1,100 molecular structures have been established by the UCSC group from the study of marine invertebrates, especially sponges and marine-derived fungi. The molecules being discovered and the strategies guiding the research continue to captivate the interests of research groups throughout the world.

Using case examples I will amplify on several circumstances. These include: (1) the general benefits derived from research in this subject area, (2) new scaffolds being explored for anti-cancer therapeutic lead development, (3) the continuing challenges to obtain sponge-derived compounds seemingly biosynthesized by microbial associants, (4) the potential and challenges associated with mining complex mixtures obtained from culture of marine-derived microorganisms, and (5) the advantages associated with using highly collaborative projects to push the research forward.

The lecture will be divided into several elements. A summary of past UCSC achievements will underscore how roadblocks have been overcome in the characterization of important biomedically important molecules. A key element in our program at UCSC has included the quest to advance marine-derived small molecules as tools to probe biological processes relevant for therapeutic lead discovery. Sketches of current projects will be used to illustrate some achievements in this area. An important new direction of the lab involves the goal to explore bioactive constituents of marine-derived myxobacterial strains. The blueprint guiding this challenging initiative is outlined below. It begins with environmental sampling along the coast of California and the subsequent steps in the process are designed to yield new chemodiversity.

Even though the quest to understand the organic chemistry of Oceana and its biota has now been ongoing for several decades, much remains to be discovered. New strategies, including those discussed here and elsewhere in the ASP2013 symposium should accelerate the process of uncovering additional first in class molecular structures. One goal of this lecture is to energize the next generation of marine bioorganic scientists to engage research driven by marine-derived molecular structures.