Marine Bioprospecting

Marine Bioprospecting: the route to treasure trove of bioresources for novel drug discovery

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By: Tapas Paul, Saurav Kumar, S.P. Shukla, Kundan Kumar and Abhilipsa Biswal*

Several marine organisms are sources of bioactive compounds. These bioactive compounds have potential applications such as molecular tools, in agrochemical industries, as fine chemicals, in cosmetics, and as nutraceuticals. Marine bioprospecting has been an important phenomenon of discovering new drugs and sustainable exploration of aquatic diversity, however it entails two major bottlenecks: sustainability and replicability. These two bottlenecks can be overcome by aquaculture of marine invertebrates. The present article developed by researchers at ICAR (Central Institute of Fisheries Education, Mumbai, India) focuses on various types of bioactive compounds produced by marine aquatic invertebrates, bio-prospecting policies, and its impacts.

The ocean is a treasury of a wide variety of untapped resources with great potential. Several marine
organisms
are sources of bioactive compounds. These bioactive compounds have potential applications such as molecular tools, in agrochemical industries, as fine chemicals, in cosmetics, and as nutraceuticals.

Marine drugs have proven to be an abundant source of pharmacologically active agents for the production of therapeutic entities against cancer, Acquired Immune Deficiency Syndrome (AIDS), inflammatory conditions and microbial disease.

“Apart from this, microalgal strains with high lipid yields are found to be valuable in the biofuel industry in the context of shrinking global petroleum reserves.”

The exploration of such biological resources of social and commercial value is known as bio-prospecting.

Tropical coral reefs are the main focus of marine bio-prospecting. These reefs form the main habitat of different marine invertebrates which are sources of potential molecules. Marine bio-prospecting entails two major bottlenecks: sustainability and replicability.

Marine Bioprospecting

Drug discovery demands large amounts of biomass leading to sustainability issues. Replicability is constrained as a result of environmental variability and community level changes to the ecology of the target organisms.

These two bottlenecks can be overcome by aquaculture of marine invertebrates. Through the culture of marine invertebrates, continuous production of animal biomass under homogenous environmental conditions can be achieved.

“Culture of microalgae strains capable of acting as sources of biodiesel can be an alternative for diesel fuel. Thus screening of bioprospecting has great application in aquaculture which can lead to an increase in global aquaculture production.”

The present article focuses on various types of bioactive compounds produced by marine aquatic invertebrates, bio-prospecting policies, and its impacts.

Phases of Bio-prospecting

Bio-prospecting can be divided into four phases: collection, identification, analysis, and commercialization.

  1. Collection. Samples and/or indigenous knowledge related to a sample are collected, and then undergo identification and isolation of compound.
  2. Identification. It includes identification and isolation of compound and characterisation of that compound.
  3. Screening and analysis. Using a variety of different technologies. It refers to screening for potential uses,
    such as pharmaceutical or other uses.
  4. Commercialisation. It is the final step which includes product development and commercialisation, including patenting, trials, sales and marketing.

Marine Bio-prospecting

The marine biomes are a rich reservoir of unique life systems for synthesizing bioactive compounds by identification and development of potential drug molecules for human therapeutics.

Oceans include a variety of extreme environmental conditions such as temperature ranging from freezing to deep hydrothermal vents (350 °C), pressure from 1-1000 atm, nutrient-rich to depleted zones and deep aphotic to upper layer photic zones.

“This variation in environmental and nutrient conditions resulted in the differential specification of organisms in each phylogenetic level from lower to higher trophic.”

Bioactive compounds are mainly found abundantly in microorganisms, algae and invertebrates, while they are scarce in vertebrates.

These compounds have shown several pharmacological properties and are used to treat diseases like arthritis, inflammation, cancer, etcetera (see Table 1).

Marine Bioprospecting

Marine Bacteria as a source of metabolites

Bacteria have played a pivotal role in the development of different drugs and antibiotics over the years. Since the discovery of Taq DNA polymerase from Thermus aquatics bacteria, thousands of products have been synthesized from various micro organisms especially bacteria which are used as antibiotics, antitumor agents, and agrochemicals.

Inspite of huge potential, marine bacteria has received less attention in the scientific community because of difficulty in non-cultivability of the majority of them (>99%).

“Marine hyperthermophilic bacteria are the source of thermo-stable proteases, lipases, esterases, starch and xylan degrading enzymes which are very beneficial in drug development.”

Several marine Vibrio species also produce a wide range of enzymes and other bioactive compounds having industrial and commercial applications. E.g. Vibrio alginolyticus which produces alkaline serine exoprotease used as detergent-resistant material and collagenase which is used in tissue culture studies.

Further, Alteromonas spp. isolated from Bermudian marine sponge produces bioactive compounds having anti-HIV potential as a reverse transcriptase inhibitor (see Table 2).

Marine Bioprospecting

Metabolites from Marine Cyanobacteria

Cyanobacteria found in marine and freshwater ecosystems are one of the richest sources of known and novel bioactive compounds including toxins with wide pharmaceutical applications. Several metabolites have been isolated from cyanophytes from freshwater species, which are cultured easily in comparison to marine organisms.

“Marine cyanobacteria are found to be a potential source of vitamin B and E which has a wide commercial value. Cyanobacteria produce several pigments such as carotenoids, phycobilins which are used as a colour enhancer, feed additives in fishes and cattles, and cosmetic industries.”

Some species such as Lyngbya lagerhaimanii and Phormidium tenueare found to produce bioactive compounds having anti-HIV activity. Scytonemin, an extracellular pigment obtained from Scytonema spp. has anti-inflammatory and anti-proliferative properties.

Further, Gambierdiscus toxicus and Ptychodiscus brevis produce several antifungal agents which have wide applications commercially. Okadaic acid produced from Prorocentrum spp. aids in studying signal transduction pathways in eukaryotic cells due to its selective protein phosphatase inhibition nature.

Metabolites from seaweeds and algae

Seaweeds are the macroscopic algae grow in the intertidal regions of the sea. Seaweeds are the only source of phytochemicals that have wide application in food, confectionery, pharmaceuticals, dairy and paper industries as gelling, stabilizing and thickening agents.

They have high protein content (35.6% in dried nori), high levels of vitamins A, B, B2, B6, B12, C, B7 and higher amounts of important minerals like calcium and iron than vegetables and fruits.

“The red alga Sphaerococcus coronopifolius was shown to have antibacterial activity; the green algae Ulva lactuca was shown to possess an anti-inflammatory compound and an anti-tumor compound was isolated from Portieria hornemannii.”

The green algae Codium iyengarii from the Karachi coast of the Arabian Sea has been found as the source of a steroid. Sargassum carpophyllum from the South China Sea is the source of two new bioactive sterols. Brown algae such as sargassum and members of laminariales mainly used in the manufacture of various goitre medicines due to their high iodine content.

Some algae, like gelidium are used for the treatment of kidney, bladder and lung diseases while laminaria is used as surgical tool in the opening of the wound due to its gentle swelling property. Some of the bioactive compounds from seaweeds and their potential applications can be seen in Table 3.

Marine Bioprospecting

Metabolites from Sponges

Sponges present in the marine environment are the source of a wide range of bioactive metabolites. Out of 11 genera of sponges in the ocean, Haliclona, Petrosia and Discodemia are commercially important due to synthesize of potent anti-cancer and anti-inflammatory agents.

Since the discovery of tumour-inhibiting arabinosyl nucleoside i.e. spongouridine from Cryptotethiacrypta, special attention is given to bio-prospecting of sponges in different countries. Some of the potent bioactive compounds from sponges are listed in Table 4.

Marine Bioprospecting

Metabolites from Cnidarians

The first breakthrough in the field of explorations of cnidarians for bio-prospecting was the discovery
of prostaglandin in corals during 1960s which has paved the way for the development of natural bioactive compounds.

Palytoxin obtained from Palythoa spp.is used as a significant tool for probing cellular recognition by potentiating metabolism of arachidonic acid and down-regulates the response to epidermal growth factor by activating a sodium pump in the signal transduction pathway using sodium as the second messenger.

Further, Pseudopetrocin-E, a tricyclic diterpene glycoside from Pseudopterogorgia spp., shows anti-inflammatory activities while Eunicea fusca containing fucoside-A used widely in cosmetic industries.

Metabolites from molluscs

Several researchers have highlighted the importance of toxins extracted from cone snails in the field of medicine and cellular biology. Conotoxins evolved from Conus spp. are the most promising bioactive compounds used in physiological and pharmacological studies.

Conotoxins block channels regulating the flow of Na+, K+ across the membranes of nerve or muscle cells, or act as antagonists of acetylcholine receptors during muscle contraction. It is more effective in relieving pain than many painkillers and aids in speedy recovery of injured nerves.

“Further, Dolabella auricularia and Chromocloris cavae produces bioactive compounds such as Dolastatin, Chromodorolide-A which exhibits antineoplastic and in vitro antimicrobial activities.”

Metabolites from Fish, Sea Snakes and Marine Mammals Marine fishes are a rich source of omega-3 fatty acids such as alphalinolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) which are used in drugs for diseases such as arthritis, heart problem and brain development.

Marine Bioprospecting

However, the reports on the synthesize of bioactive compounds from fishes and marine mammals are scarce. Tetradotoxin (TTX) is an important compound extracted from puffer fish which has wide application in the pharmacological industry and for researchers studying voltagegated sodium channel.

Electric rays produce ciguatoxin which is used as a potent antidote for pesticide poisoning. Squalamine, a water-soluble broad-spectrum antibiotic is extracted from the stomach of dogfish shark, Squalus acanthias. The sea snakes produce Fu-anntai, an anticancerous drug, which has antiblastic effects on cervical carcinoma, stomach cancer, rhinocarnoma and leukemia cells (see Table 5).

Marine Bioprospecting

Merits of marine bio-prospecting

Marine bio-prospecting has been an important phenomenon of discovering new drugs and sustainable exploration of aquatic diversity.

• The economic viability of marine bioresources for pharmaceutical purposes is enormous and has
a scope for benefiting not only the pharmaceutical industries engaged in R & D but also the native country and indigenous communities.

• Discovery of several life-saving drugs including anti-neoplastic drugs (e.g. vinblastine, taxol, topotecan, and etoposide) in recent past has renewed the interest of pharmaceutical industries in bio-prospecting.

Marine bio-prospecting collaborations between pharmaceutical companies and countries supplying the medicinal raw material and knowledge offer not only the revenue source for under-developed countries but also opportunities for the society for better education and employment avenues.

Limitations

• The multinational companies engaged in bio-prospecting are free to patent bio-materials but there are no effective guidelines and conditions defined for recognizing and rewarding the contributions of indigenous people and other informal innovators who are responsible for nurturing, using and developing biodiversity.

• Genetic material imbalance in the ecosystem due to excessive exploitation of material resources.

Threats and impacts of marine bio-prospecting

  • The current tendency of researchers and industries to generate novel products is likely to be threatened by the loss of the basic resource, biodiversity, at all levels: genes, populations, species, and ecosystems. The loss of biodiversity may not only lead to a loss of commercial opportunity but may also alter ecosystem structure and function.
  • Losses of traditional knowledge of marine biological resources are one of the major threats to bio-prospecting.
  • Use of bottom trawlers for fishing results in the destruction of non-target fish species at dwelling at sea bed such as molluscs, cnidarians, echinoderms and also disturbs the aquatic plants, coral reefs etc.
  • Biopiracy has been coined to reflect the illegal appropriation or exploitation of genetic and biochemical resources. It must be included, in any case, that the absence of appropriate implicit rules, the absence of proper enactment, and the absence of national ability to deal with biodiversity use issues in the larger part of biodiversity-rich nations are factors empowering biopiracy.
  • Overharvesting is a difficult issue in a few areas, particularly when it includes marine animals or seaweeds for medications and pharmaceuticals. Some marine species have likewise been overharvested for research. Specifically, cone shells of the molluscan family Conidae are prized for their toxins (conotoxins) for application to numerous regions of medication, including tumour control, disease treatment, and microsurgery.

Marine Bio-prospecting policy

Bio-prospecting should be regulated, both at the national and international level, based on the principles of the Convention on Biological Diversity, conservation of biodiversity, sustainable use of its components and fair and equitable sharing of the benefits arising out of the utilization of genetic resources. Various legal instruments and organizations related to coastal genetic resources regulation are as follows:

  • Convention on Biological Diversity (CBD)
  • Bonn guidelines and Nagoya Protocol
  • United Nations Convention on the Law of the Seas (UNCLOS)
  • International Sea Bed Authority
  • Global Ocean Commission
  • European Science Foundation
  • Valencia Declaration

Conclusion

Bio-prospecting plays an integral role in discovering novel molecules that leads to drug development. Nature will give original novelty and quality which will be changed within the laboratory. “Poison kills the poison,” the renowned byword is that the basis for researchers to find the medicine metabolites from living organisms.

The scientists in different parts of the world have extracted various drugs for such diseases in recent years. Despite the limitations and allegations of bio-piracy, the bio-prospecting with its potential as a rich and important source of new therapeutic agents is an important tool for drug discovery and research.

However, for a healthy environment and proper bio-prospecting, the collaborations between the pharmaceutical companies and the countries supplying the indigenous knowledge and medicinal resources should be regulated for a mutually beneficial relationship.

*ICAR-Central Institute of Fisheries Education, Mumbai-400061, Maharashtra, India.
Correspondence author: saurav@cife.edu.in.
References cited by the authors in the article are available under previous request to our editorial team.

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