1. Marine Natural Products & Human Health Robert R. Bidigare University of Hawaii

2. Searching the oceans for new products Marine Nutraceuticals (nutriceuticals are supplements such as vitamins, minerals, herbs that offer health benefits). & Cosmeceuticals (compounds used in cosmetics) - Lipids (PUFAs and carotenoids) PUFA - Polyunsaturated fatty acids that are more healthful than saturated fats. Carotenoids -natural fat-soluble pigments that occurs in plants. Carotenoids are antioxidants that are important for healthful diets. - UV blockers- chemicals that block UV light - Food additives and stabilizers

3. Fats are organic compounds that are freely soluble in organic solvents Specific examples include: fatty acids, triglycerides, phospholipids, waxes, hormones, vitamins, sterols, and carotenoid pigments Definitions –Fatty acids - major component of fats which are used by the body for energy and tissue development –Triglycerides - the body's storage form for fat –Carotenoid pigments- the yellow to orange pigments in nature that have health – benefits –Phospholipids - the building blocks of cellular membranes. Chemicals of interest Lipids (fats)

4. Fatty Acids (FAs) SFAMUFAPUFA FA’s are12 to 28 carbon chain lengths. The diagram illustrates the biochemical structure differences between saturated,(SFA),monounsaturated (MUFA) and polyunsaturated (PUFA)

5. Lipids in Marine Microalgae Lipids of interest occur in microalgae Possess a very large proportion PUFAs Unique to this group are EPA and DHA omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3fatty acids are also beneficial for healthful diets. Pinguiococcus pyrenoidosus

6. EPA & DHA “Omega-3 fatty acids”, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Beneficial effects: –Lowers the incidence of certain cardiovascular diseases –Improves neural and retinal development in infants - Slows growth of cancerous cells

7. Carotenoids Carotenoids ( precursors of vitamin A, they are the red and orange pigments found in vegetables such as carrots, algae and other plants. ) Carotenoid examples include astaxanthin, zeaxanthin, lutein and ,  -carotene Carotenoids are now being used as fish/shrimp/poultry feed ingredients for enhancing the color of animal flesh and egg yolks Astaxanthin

8. Carotenoids Carotenoids have tremendous potential as pharmaceutical products since they have strong anti-oxidant activity. Anti-oxidants are believed to help prevent cancer and keep cells healthy.

9. Carotenoids Other Important aspects of Carotenoids. They are effective for the preventive treatment of cancer and age-related macular degeneration, which is the deterioration of the retina that can cause blindness)

10. Marine Sources for High-value Carotenoids Green Algae (Dunaliella salina) Bacteria (Erythrobacter longus) HL = high light C = control

11. Commercially Available Carotenoid Products

12. Other compounds found in algae that are of interest UV Blockers: MAAs (Mycosporine-like amino acids) (MAAs) are photo-protective compounds in marine algae. High-value additives for paints, plastics & cosmetics

13. Agar-Agar: Used for the production of emulsions and bacteriological culture mediums Carrageen: Used for the production of ice cream, cosmetics, chocolates, coconut butter, milk products, syrups and gels Other products from algae: Food Additives and Stabilizers

14. Marine Microbes: An Untapped Resource for Pharmacological Lead Compounds? The 3 Domains of Life (D. M. Karl)

15. Drugs from the sea: Biochemicals isolated from marine organisms that are in use or are being developed ApplicationOriginal SourceStatus Anti-viral drugs (herpes infections) Sponge, Cryptotethya cryptaCommercially available Anti-cancer drug (non- Hodgkin’s Lymphoma) Sponge, Cryptotethya cryptaCommercially available Anti-cancer drugBryozoan, Bugula neritinaPhase II clinical trials Anti-cancer drug (mitotic inhibitor) Sea hare, Dolabella auricularia Phase I clinical trials Anti-cancer drug (tumor cell DNA disruptor) Tunicate, Ecteinascidia turbinata Phase III clinical trials Anti-cancer drugTunicate, Aplidium albicansAdvanced preclinical trials Anti-cancer drugGastropod, Elysia rubefescens Advanced preclinical trials Anti-cancer drug (microtutule stabilizer) Sponge, Discodermia dissoluta Phase I clinical trials Anti-cancer drugSponge, Lissodendoryx sp.Advanced preclinical trials Anti-cancer drugSponge, Micromonospora marina Advanced preclinical trials

16. (D. M. Karl)

17. MARINE MICROBIAL DIVERSITY Current research is discovering vast quantities of microbes (bacterioplankton) that are like bacteria but behave like plants in that they capture energy from the sun Phylogenetic diversity Metabolic peculiarities Habitat/Niche Space (D. M. Karl)

18. POST-1978: NOTHING SHORT OF A MARINE MICROBIOLOGICAL REVOLUTION! 1979: Discovery of Synechococcus (Waterbury) Marine unicellular cyanobacteria of the Synechococcus group occupy an important position at the base of the marine food web: they are abundant in the world's oceans and as a result are major primary producers on a global scale and one of the most numerous genomes on earth 1988: Discovery of Prochlorococcus (Chisholm) Prochlorococcus is the smallest known phototroph it contributes 30-80% of primary production in the world's oligotrophic oceans, and is consequently plays a significant role in the global carbon cycle and the Earth's climate. 1990: Discovery of SAR-11 (Giovannoni) About ten thousand bacterioplankton of the type SAR 11 are found in every drop of seawater. Scientists are only beginning to understand what these organisms do. (D. M. Karl)

19. Less than 1% of species Only 1 “model” system (E. coli) Novel microbes and habitats Novel physiology/ biochemistry Knowns Unknowns Exploring the oceans: NOT EVEN THE TIP OF THE ICEBERG! T. Newberger (D. M. Karl)

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