Marine Natural Products Lecture Notes

Introduction

• Speaker: Dr. Paul Jensen, Professor at Scripps Institution of Oceanography
• Focus: Microbes in the ocean and their natural products (compounds produced by marine organisms)
• Importance: Basic questions about species biogeography and chemical ecology; applied research in drug discovery.

Communication in the Ocean

• Chemical language, not verbal communication.
• Organic chemistry as the basis: Carbon-based chemistry is crucial.

Biochemistry vs. Natural Products Chemistry

• Primary Metabolism: Fundamental processes shared by all life forms for energy (carbohydrates breakdown).
• Secondary Metabolism: Production of natural products; complex structures built from intermediates of primary metabolism.

Functions of Marine Natural Products

• Ecological Roles:
  • Defense mechanisms against predators.
  • Nutrient acquisition, mate recognition, and settlement cues.
• Examples:
  • Oysters use chemical cues for larvae settlement.
  • Crabs use chemicals for mating and to suppress cannibalistic instincts.
  • Copepods use pheromones for locating mates.

Chemical Defense in Marine Organisms

• Brightly colored organisms often have chemical defenses (warning predators).
• Leaf Cutter Ants: Use antibiotic-producing bacteria for protection against parasitic fungi.
• Coral Reefs: Complex interactions; organisms develop mechanisms to avoid predation.
  • Assays to test for chemical defenses show potential medicinal properties.

Marine Natural Product Drug Discovery

• Began seriously in the 1970s with collections of marine organisms.
• Findings include anti-cancer compounds derived from marine sources (e.g., sponges, sea hares, cone snails).
• Challenges with supply and synthesis of complex molecules.

Microbial Sources of Medicinal Compounds

• Interest in oceanic microbes as a source of new medicines.
• Actinomycetes: 50% of antibiotics discovered come from this group; exploration in ocean sediments.
• Discovery of new genus Salinaspora from ocean sediments; its potential in drug discovery.

Salinaspora and its Compounds

• Salinaspora produces unique secondary metabolites with potential medicinal uses.
• Salinasporamide A: Potent proteasome inhibitor; potential cancer treatment.
• Currently in Phase 3 clinical trials under the name Marizomib.

Advancements in Drug Discovery Techniques

• Transition from traditional methods to genome mining:
  • Genome sequencing helps predict which microbes can produce interesting molecules.
  • Bioinformatics assists in identifying potential candidates for drug discovery.
• Synthetic biology: Engineering microbes to express silent genes for better yields of natural products.

Conclusion

• Exciting prospects in marine microbiology and drug discovery.
• Collaborative research efforts across UC campuses to enhance drug discovery.
• Acknowledgment of students and colleagues at UC San Diego for their contributions.