MARINE NATURAL PRODUCTS

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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
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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
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