MARINE NATURAL PRODUCTS CHAPTER TWO : MARINE NATURAL PRODUCTS CONTENTS 2.1 Valuable chemicals 2.2 Bioactive compounds from micro-algae 2.3 Marine biomedical and bioactive compounds from marine organisms 2.4 Anticancer – antiviral – antibacterial – antifungal compounds 2.5 Biopesticides, herbicides from Marine Microbes MARINE BIOPROSPECTING DEFINITIONS • Marine natural products = organic metabolites isolated from marine organisms; • Secondary metabolites = metabolites not known to be involved in primary metabolism; WHY ARE ALGAE INTERESTING ? • Marine algae are photosynthetic organisms with relatively simple structure • Great species diversity – 25000 – 30000 species • Exists as unicellular ( micoralgae ) organisms to multicellular with great size ( macroalgae) • Live in complex habitats submitted to extreme conditions where algae needs to adapt to survive, producing a great variety of secondary ( biologically active ) metabolites with structures that cannot be found in other organisms. • Algae can be a very interesting natural source of new compounds with biological activity that could be used in foods, cosmetics, pharmaceuticals, etc. • Possibility of collecting (harvesting) different species throughout the year • Important natural reactors: can be used at large scale to produce active compounds. • In the world, around 7 billion Tons of algae (net weigth) are processed. Cyanobacteria (“Blue-Green Algae”) Photosynthetic Bacteria Oldest Organisms on the Earth (Fossil Record - 3.5 Billions Years!) Marine, Freshwater and Terrestrial Stromatolites Symbiosis - e.g. Lichen Cyanobacteria Cyanobacteria First Scientific Report of Toxic Cyanobacteria: George Francis (1878) Nature Lake Alexandria, Murray River, Australia “thick scum like green oil paint, some two to six inches thick, and as thick and pasty as porridge” “Unwholesome” for cattle and other livestock that drink at the water Nodularia spumigens Toxins from Cyanobacterial HABs Neurotoxins Hepatotoxins Dermatotoxins Medical Applications of Aquatic Biotechnology • A wide number of marine species contain compounds of biomedical interest including: – Antibiotics – Antiviral molecules – Anticancer compounds – Insecticides • These species include: - Sea sponges – Cyndarians, which include hydras, jellyfish, sea anemones, and a variety of corals – Molluscs, which includes snails, oysters, clams, octopuses, and squids – Sharks • Members of these phyla are of particular interest due to the immune defense mechanisms which are adapted to a sessile life style Success Stories Marine Organisms : A Source of New Drug Leads Good news : • Marine organisms- prolific source of novel bioactive agents Bad news : Sustainable supply of natural product problematic – Low concentration in natural source – Environmental issues of large scale harvest – Great structural complexity prohibits chemical synthesis Methods of Supplying Marine Natural Products Chemical methods: – Synthesis Biological methods: – Harvesting from nature – Aquaculture – Recombinant technologies – Cell culture (associated microbe or invert. host) Technology Advantages Problems: – Sustainable source of bioactive compounds – Avoids large scale collecting from nature Current solutions: – Large scale collections Advantages over state-of-the-art: – Sustainable production methods of drug candidates – Inexpensive large scale production of drug candidates – Avoid environmental disasters Medical Applications of Aquatic Biotechnology • Osteoporosis, a condition characterized by a progressive loss of bone mass creates porous and brittle bones that can lead to fractures of the hip, legs, and joints, which severely hinder an individual's lifestyle • Over 90% of the roughly 25 million Americans affected by osteoporosis are women • A common treatment for osteoporosis is human recombinant calcitonin, a thyroid hormone that stimulates – Calcium uptake – Bone calcification – Inhibits bone-digesting cells called osteoclasts Medical Applications of Aquatic Biotechnology • Recently, researchers have discovered that some species of salmon produce a form of calcitonin with a bioactivity that is 20 times higher than that of human calcitonin • Cloned forms of salmon calcitonin are now available for delivery as an injection form and a nasal spray Sustainable Approaches for Pseudopterosin Production Recombinant technology: – Labour intensive development – Long term planning – Cheap, scalable production – Environmentally save production Algae Cell Culture: – Long term planning – Cheap, scalable production – Environmentally save production – Quickly adaptable to other organisms and natural product sources Method 1: Production of pseudopterosins by recombinant technologies • Identify biochemical pathway of pseudopterosins production • Isolate/Characterise enzymes catalysing biosynthetic steps • Clone biosynthetic enzymes into host organism – E.coli, yeast or plant • Mass production of pseudopterosins using recombinant organism Nonmedical Products • Bacteria living near hydrothermal vents (hot water geysers on the ocean floor) have yielded a second generation of heat-stable enzymes for use in PCR and DNA-modifying enzymes including ligases and restriction enzymes • Some enzymes are salt-resistant – Which renders them ideal for industrial scaleup procedures involving highsalt solutions • Researchers have discovered marine species of Vibrio (gram-negative bacteria) that produce a number of proteases – including several unique proteases that are resistant to detergents used in many manufacturing processes • As a result, these detergentresistant proteases may have potential applications for degrading proteins in cleaning processes – Including their use in laundry detergent for removing protein stains in clothes Nonmedical Products • Another product of the sea is carrageenan – Which is listed as an ingredient in many preserved foods, toothpaste, and cosmetics – This sulfate-rich polysaccharide, extracted from red seaweeds, has been used in many products for over 50 years • Carrageenans have been used as thickening agents and for improving food texture • Some of the most common applications of carrageenans include their use as stabilizing and bulking agents in – – – – – – – – – – Chewing gum Chocolate milk Beers and wine (to improve the clarity of these drinks) Salad dressing Syrups Sauces Processed lunch meats Adhesives Textiles Polishes, and hundreds of other products. Prialt™ Prialt (SNX-111) is a synthetic form of the omega-conotoxin MVIIA It is 100-1000x more potent than morphine It has been approved for use by the FDA for chronic pain