Marine Natural Products: From Sea to Pharmacy

The lecture begins with Harry Hellings, executive director of the Birch Aquarium at Scripps, introducing Dr. Paul Jensen, a professor and section head for biological research at the Scripps Institution of Oceanography. Dr. Jensen's work focuses on marine microbes and their natural products, which are compounds produced by these organisms that have potential applications in various fields, including drug discovery. His research encompasses basic biological questions about species and biogeography, as well as applied research on chemical ecology and drug discovery.

Dr. Jensen explains that the ocean's primary language is chemical, not verbal. He delves into the basics of organic chemistry, which is the study of carbon-based compounds, and how this relates to the natural products produced by marine organisms. The diversity of these organic molecules is crucial for inter-species communication and ecological roles, such as defense mechanisms, nutrient acquisition, and settlement cues. The distinction between primary and secondary metabolism is also discussed, with the latter being the source of complex natural products that have potential pharmaceutical applications.

The paragraph explores the various defense mechanisms and chemical cues used by marine organisms. Examples include female crabs releasing chemicals to attract males for mating while also suppressing their feeding instincts to avoid cannibalism. Another example is copepods using pheromones to find mates in the open ocean. Defense in the context of chemical compounds is also discussed, with a focus on how these compounds can be a source of new drugs, as seen in the case of the leaf cutter ant and its use of bacteria to produce antifungal agents.

Dr. Jensen discusses the history and process of marine natural product drug discovery, which began in the 1970s with extensive collection and study of marine organisms for their unique molecules. The challenges of supply and synthesis of these complex molecules are highlighted, as well as the success stories of drugs derived from marine sources that are now in clinical use. The importance of understanding the ecological roles of these molecules is emphasized to aid in the discovery of new pharmaceuticals.

The paragraph focuses on the cultivation of marine microbes as a solution to the supply problem of lead molecules for drug development. It discusses the historical importance of microbes as a source of antibiotics and the potential of ocean microbes to provide new medicines. The search for actinomycetes in ocean sediments and the discovery of new species, including the Salinispora genus, are detailed. The unique characteristics of these bacteria, such as their requirement for seawater to grow, suggest their adaptation to the ocean environment and the potential for producing novel molecules.

Dr. Jensen introduces the concept of genome mining, a modern approach to discovering new drugs from marine microbes. By sequencing the genome of bacteria, researchers can predict the structures of potential molecules without first culturing the organism. This method allows for a more targeted and efficient search for new molecules with pharmaceutical potential. The paragraph also discusses the collaboration between different UC campuses to combine genomics, microbiology, and natural products chemistry in the search for new drugs.

The final paragraph delves into the evolutionary aspects of marine microbes and their natural products. It discusses how genomic sequencing can reveal the evolutionary history of the ability to produce certain molecules and how different species may produce different versions of these molecules. The importance of understanding the ecological roles and the conditions that trigger the production of these molecules is emphasized. Dr. Jensen also mentions the unsuccessful attempt to culture ancestral bacteria from deep-sea sediments, which would have provided insights into the evolution of their chemical defenses.

The lecture concludes with an acknowledgment of the collaborative nature of the work and the importance of multi-campus research programs. Dr. Jensen expresses his appreciation for the opportunity to work with talented students and colleagues at UC San Diego. He invites questions from the audience, covering topics such as the techniques used to determine the structure of molecules, the habitat of the bacteria, the clinical trial status of a molecule, and the potential reasons behind the production of powerful eukaryotic cell-targeting compounds by marine bacteria.