DOI:10.21884/IJMTER.2018.5089.49FPR 210
APPLICATION OF NATURAL MARINE MATERIALS:
OPPORTUNITIES AND CHALLENGES
Anna Shaliutina-Kolesova1,2
, Olena Shaliutina2, Saeed Ashtiani
1,Yue Sun
1, Mo Xian
1 and Rui
Nian1
1CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology,
Chinese Academy of Sciences, No. 189 Songling Road, Qingdao 266101, China 2University of South Bohemia in České Budějovice, Faculty of Fisheries and Protection of Waters, South
Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture
and Hydrobiology, Zátiší 728/II, 389 25 Vodňany, Czech Republic
Abstract- Hundreds of compounds from structurally-diverse and biologically-active secondary
metabolites of marine organisms are discovered annually, several of which have inspired the
development of new classes of therapeutic agents. Recent advances in molecular and cell biology,
biophysics, nanotechnology, and materials science, along with innovative experimental techniques and
equipment have allowed isolation of extracts from marine materials. As with all emerging technologies,
challenges must be overcome if natural product biotechnology is to reach its full potential, first among
these being establishment of practical approaches to acquisition of complex marine organic molecules
for clinical evaluation and development. In this review, we provide examples of current and potential
applications of compounds from aquatic organisms in various fields of industry and describe strategies
for biomedical use of biologically active compounds from marine organisms. We identify the primary
challenges to discovery of materials and development of pharmaceuticals from marine sources.
Keywords-marine materials,micro-organisms, bioactivity, macro-organisms
I. INTRODUCTION
The marine environment is an unusual reservoir of organisms.Marine organisms are adapted for
an environment that may include high salt concentration, low temperature, high pressure, and low
nutrient availability. These extremes require unique strategies, leading to the development of structures
and physiology that differs from terrestrial organisms [1]. Therefore, in the last 30 years the need for
new therapeutic molecules has given rise to a vast number of studies in marine fish, invertebrates and
microbes [2]. In this regard, each year an increasing number of novel marine metabolites are reported;
new compounds are isolated from aquatic organisms and proposed as novel products for personal care,
cosmetic use, agriculture and health.
The oceans represents a huge sourceof plants, animals, and micro-organisms that could provide
different biomaterials with a wide range of biological actions such as anti-tumor, anti-microtubule, anti-
proliferative, photoprotective, antibiotic, and anti-infective [3,4]. In the results reported by Newman and
Cregg marine natural products have been shown as the biggest source of anti-cancer drugs [5].
Moreover, marine biomaterials have been demonstrated as promising scaffolds for bone tissue repairing,
development of artificial organs and also as a wound dressing materials [6]. Therefore, due to their
high-value ingredients for human health, in recent decades researchers have more focused on the
application of marine substances in the medical and pharmaceutical field.
Although the marine environment represents a unique source of biologically active compounds
and materials for the pharmaceutical and medical industry, their harvest and use presents challenges.
Martins et al categorized the major challenges faced in identifying and developing new bioactives and
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biomaterials from marine sources as: (i) biodiversity, associated with secure access to marine resources;
(ii) supply and technical issues associated with the process of isolation and sustainable production of the
pure bioactive, and the understanding of its mechanism of action towards the desired target; and (iii)
market challenges involving the process and the costs of developing of marine bioactive [7].
In this review, we discuss the use of marine organisms in various fields of industry, outline the
application of biologically active compounds from marine organisms in medicine and pharmacology,
and provide an overview of the challenges hindering their discovery and exploitation.
II. POTENTIAL APPLICATION OF MARINE ORGANISMS
The marine environment, due to its biodiversity, is a rich natural source of biologically active
compounds [8]. Many marine organisms live in complex habitats exposed to extreme conditions [9] and,
in adapting to the environment, produce a wide variety of biologically active metabolites and
compounds with potential for practical applications (Fig.1). Annually 65-70 million tons of seafood
including fish, shellfish, crustaceans, and edible algae is harvested for commercial uses [10].
Figure1. Major fields of marine product application.
Fish represent a substantial sector of economic development. Fish and fish products have a wide
range of applications. Foremost, it is one of the most versatile food commodities [11]. Byproducts of the
fish processing industry such as skin, bones, and scales, have attracted interest as well. Skin as a source
of gelatin is used in the pharmaceutical industry as an alternative to mammalian gelatin [12]. Fish
collagen presents advantages over bovine collagen [13]. Abowei and Ezekiel demonstrated that a
substance found on fish scales, usually herring, can be used for pearlescent effects, primarily in nail
polish; however it is rarely used due to its prohibitive cost [14]. The oil from fresh liverof cod Gadus
morrhua and halibut Hippoglossus hippoglossu) is used in vitamin A and D therapy. Squalene, present
in large quantities in shark liver oil, can be employed as an antimicrobial, immune system enhancer, as
an intermediate in the manufacture of pharmaceuticals, and an adjuvant in vaccines [15].
Fish-produced toxins have also received consideration. Tetrodotoxin, a highly toxic low
molecular weight substance is produced by symbiotic bacteria in certain puffers, ocean sunfish, and
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porcupine fish. This toxin has potential for the treatment of neuropathic pain, and is currently in Phase
III clinical trials [16]. In addition, fish is an important component of many animal feeds, particularly as
fishmeal.
Exploitation of marine invertebrates, including mollusks, arthropods (crustaceans), and
echinoderms comprises a major sector of the world economy. The ocean contains more than 200 000
described species of invertebrates [17]; however, it is estimated that this number is a small percentage of
the total number of species that have yet to be discovered and described [17].
Reduction in fish stocks has increased interest in non-fish hydrobionts that can fill the deficit in
protein foods [11]. Cephalopod mollusks are the most commercially valuable, containing a complex of
nutrients and biologically active substances [18]. Squid is one of the most numerous cephalopods, and
represent the most important global reserve of high-quality protein [19]. The muscle tissue of squid
contains water-, and salt-, and alkali-soluble protein fractions [20]. Squid protein values are almost
twofold those of carp muscle tissue. The meat of cephalopods contains the essential amino acid taurine,
which is widely used in medicine for the treatment of cardiovascular disease and diabetes [21]. The meat
of cephalopods contains the essential amino acid taurine, which is widely used in medicine for the
treatment of cardiovascular disease and diabetes [21]. Moreover, taurine provide an increasing of
physical activity, stimulation of brain action, cognition, memory and attention [22] and is often used in
the food industry as a component of energy drinks and athletic performance enhancing supplements.
Carbon derived from snail shells is inexpensive and has the advantage of withstanding
temperatures to 1000 ºC without being converted completely to ash [23]. Removal of organic
contaminants from industrial waste currently uses expensive adsorbents. The use of modified snail shell
as an adsorbent, especially in the removal of heavy metals such as lead, could reduce cost of treatment.
Corals are marine invertebrates that support extraordinary biodiversity and are home to a
multitude of fish and invertebrates. Corals are an important commercial product in bone graft material
production and exhibit biocompatibility properties [24]. Anti-inflammatory pseudopterosin from soft
coral Pseudopterogorgia elisabethae is as a classic compound in cosmetic products [25]. Coral-derived
medical products have been used for surgical applications such as spinal fusion [26], maxillofacial
surgery [26, 27], dental surgery [28], and orthopedic applications [29]. In addition, creatures found in
coral ecosystems are important sources of new medications to induce and ease labor as well as to treat
cancer, arthritis, asthma, ulcers, bacterial infections, heart disease, and viruses and are sources of
nutritional supplements and enzymes [30]. The medications and other potentially useful compounds
identified have led to coral ecosystems being referred to as the medicine cabinet of the 21st century, and
the list of potential and approved new drugs is growing.
Marine plants like microalgae and macroalgae have enormous ecological importance and
represent a significant proportion of the world’s biodiversity [31]. They can be categorized according to
color: the Rhodophyceae (red algae), the Phaeophyceae (brown algae), the Cyanophyceae (blue-green
algae), and the Chlorophyceae (green algae). The diversity in the biochemical composition of seaweeds
is mostly connected with nutritional (functional foods), supplemental (animal feed) or
ethnopharmacological (raw material for pharmaceutical and cosmetics industry) uses and as it possible
in therapeutic applications [32, 33]. In agriculture, products based on marine algae are applied to
improve plant growth and productivity. Mugnai et al reported that extracts of bioactive substances from
marine seaweed can be used to avoid excessive application of fertilizers and improve nutrient uptake
through the roots and leaves [34]. The potential of seaweed in cosmetics have provided insight into
biological activity of marine algae in promoting skin health and appearance [31].
Marine sponges represent a fertile source of natural bioactive substances with broad diversity of
primary and secondary chemical components and metabolites [35] Marine sponges produce a wide array
of antitumor, antiviral, anti-inflammatory, immunosuppressive, antibiotic, and other bioactive molecules
that have the potential for therapeutic use. It has been shown that different components affect targeted
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diseases by different mechanisms (e.g., microtubule stabilization or interaction with DNA to combat
tumors). Marine sponge derived biomaterials show promise in artificial organ development [36]. Wang
et al reported that marine sponge biogenic silica aids in differentiating stem cells into osteogenic cells
and has potential for use in bone tissue construction [37]. Sponge collagen can be used for nano-
biotechnological applications. For example, Nicklas et al developed nanoparticles of Chondrosia
reniformis sponge collagen as penetration enhancers for the transdermal drug delivery that can be
applied in hormone replacement therapy [38]. Produced collagen with chitosan/hydroxyapatite from
marine sponge (Ircinia fusca) has been developed for bone tissue engineering in vitro [39]. Sponges are
also a useful tool for dry cleaning of frescoes and paintings. It is used for painting to create decorative
effects and set on rollers to extend color on walls, canvases and large surfaces. In footwear manufacture
it is used to gently extend the color on the upper part of the shoe and for polishing and finishing of the
shoe. Additionally, there are numerous studies on the applications of sponges as a product for personal
hygiene, because they have many natural properties and most of all does not give allergic reactions [40].
Marine organisms have proven to be a valuable source of materials in various fields of industry. With
the recent advances in molecular and cell biology, biophysics, nanotechnology, and materials science,
innovative experimental techniques and equipment have been developed to isolate extracts from marine
materials [41]. These purified compounds exhibit therapeutically and industrially significant biological
actions. In addition to manufacturing, agriculture, nutrition and food supplements, and other marketable
products, the greatest application of marine organisms has been in medicine.
III. MARINE ORGANISM POTENTIAL IN MEDICINE
Marine organisms are still remain a largely unexploited resource in biotechnology and medicine.
However, based on the previous data [36, 42] it is known that many important marine organisms such as
fish, invertebrates, reptiles, fungi and corals are composed of molecules and materials exhibiting
characteristics and properties that allow to use them for surgery, tissue engineering and development of
novel medications.
Figure2. Classification of marine organisms and their applications to medicine.
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Bioactive secondary metabolites from marine habitat of diverse classes of organisms have been
explored and contribute in varying proportions, including algae/microalgae (cyanobacteria and diatoms)
(9%), bacteria (18%), and sponges (37%) [43]. Enzymes produced by marine algae, bacteria, fungi, and
sponges exhibit physiological properties such as hyperthermostability, barophilicity, salt and pH
tolerance, adaptations to extreme cold, and novel chemical and stereochemical properties [44]. Research
has shown marine metabolites to act as antitumor, antiviral, and enzyme inhibitory agents, affecting the
central nervous system and respiratory, neuromuscular, autonomic nervous system, cardiovascular, and
gastrointestinal systems [45]. Marine polysaccharides are known material to form a scaffold-forming
property, which can be useful to treat loss of organs and their regeneration [46]. Therefore, because of
their naturality, biocompatibility, nontoxicity and biological functionality many components from
marine macro and microorganisms are universally applicable material for various medical uses.
3.1. Macro-organisms
Marine biotechnology has enormous potential for the development of novel products in the
medical device and biomaterial markets. Marine macro-organisms play a dominant role in applications,
mainly in medicine.
Corals.
Corals are a broad group of marine invertebrates that deposit a mineral skeleton as they grow.
Corals used for medical applications are limited to a select number of genera. The porous lumpy variety
and slender are the most commonly used. Both are red. The main component of corals is primarily
calcium carbonate and small amounts of magnesium, iron, and phosphorous [47]. Corals are medicinally
very important in bio-medical research as they are put to use for treatment of AIDS, pain and other
anomalies. Moreover, it is believed that corals are an excellent means to relieve fatigue and improve
vitality [48]. Additionally, they improve memory, have a beneficial effect on the organs of sight and
hearing, and strengthen the nervous system and help get rid of insomnia [49]. Specialists in the field of
phytotherapy claim that corals promote the improvement of blood circulation and the functioning of the
cardiovascular system. In some countries coral is used as a contraceptive.
Sea corals of some species possess anatomical structure, physical, and chemical characteristics
that simulate human bone [50]. For example, as mentioned above, corals contain calcium carbonate that
make them to be useful biomaterials for bone substitutes in periodontal surgery [50]. In work by
Moreira-Gonzalez et al it has demonstrated that substitute osteoconductive synthetic bone graft material
such as coralline hydroxyapatite is manufactured by the hydrothermal conversion of the calcium
carbonate skeleton of coral that preserving the original porous structure and is similar to that of bone
[51]. Applications for coralline calcite and aragonite have been reported in replacement of fractured
bone, via their ability to form a strong chemical bond with soft tissue and bones in vivo [52]. The
advantage of using coralline apatite is increased chances of resorption by the attack of enzymes,
especially carboanhydrase [53]. Coral ash is used as a local astringent in preparation of tooth powder,
for the treatment of cancer of breast, lungs, stomach, and uterus and for treating anemia, high fever, and
hemolytic jaundice [47]. Use of porous coral apatite has been established for the in vitro culture of
prokaryotic and eukaryotic cells [54].
Seaweed.
Marine seaweed is a source of commercially important biomaterial. Algae contain substances
such as phytohormones, amino acids, polyunsaturated fatty acids, polysaccharides, and minerals
including calcium, magnesium, iodine, sodium, silicon, manganese, phosphorus, and sulfur [55].
Investigations into the metabolites derived from algae have revealed their potential antioxidant [56],
antidiabetic [57], antitumor [58], and anti-allergic [59] properties, as well as their role in hyaluronidase
enzyme inhibition [60], neuroprotection [61], and matrix metalloproteinase inhibition [60]. A sulfated
polysaccharide from the red marine algae Champia feldmannii (Champiaceae) has been shown to
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possess edematogenic activity, in conjunction with an increase in vascular permeability and leukocyte
migration in the rat peritoneal cavity [62]. Polymers of sulfated polysaccharides extracted from brown
algae (fucans) showed potent inhibition on the human complement system in vitro [63].
Sponges.
Sponges are also potential sources of biomaterials with applications to medicine, especially as a
novel bone replacement biomaterial [53]. Dry sponge consists of gelatin, albumin, and iodine. Its ash
mixed with oil is applied to swollen glands and is given internally in treating dysentery [47]. An
example is the Okinawan sea sponge Okinawan plakortis, from which a tyramine-containing
pyrrolidine, alkaloid-placoridin A (plakoridine A), is obtained, which shows significant potential as a
cytotoxin in lymphoma [64]. Substances isolated from the subtropical redbeard sponge Microciona
prolifera have been shown highly effective in the treatment of tuberculosis [25]. Both water- and fat-
soluble substances are produce from these sponges. The first is used as an inhaler for the nasopharynx
and respiratory tract, and the second for lubricating the mucous membranes. In both cases, a significant
therapeutic effect was revealed. Nucleosides (spongothymidine, spongouridine) obtained from the
Caribbean sponge Tectitethya Crypta (or Cryptotethya Crypta and Tethya Crypta), of class
(Demospongia), provide the basis for antiviral and anticancer drugs, in particular leukemia. A substance
isolated from this sponge also proved effective in the treatment of viral encephalitis [65]. Recently
discovered agents including anticancer, antichemotactic and antifoulingproduced by many species of
sponges have also gained attention in medicine [53].
Crustaceans.
Marine crustaceans such as crab, shrimp, krill, lobster, and prawns provide a source of the
important polysaccharides, chitin and chitosan [66], widely used in medicine [67]. Microparticles in
crab, shrimp, and lobster shells have been shown to have antibacterial activity and anti-inflammatory
mechanisms that could lead to the development of novel preventive and therapeutic strategies [68].
Chitin is a nitrogen-containing linear polymer. It is an animal analogue of cellulose and has similar
composition and structure and performs similar structural and support functions in organisms. Organic
synthesis allows creation of many valuable materials based on chitin, including surgical threads and
biocompatible biodegradable films with bactericidal and regenerative action [69]. They are used in the
treatment of wounds and severe burns and in drugs to stimulate intestine activity and to reduce the level
of uric acid via chitin’s ability to bind to bile acid, the means by which absorption of cholesterol takes
place [69].
Tunicates, or sea squirts, evolved the notochord over 540 million years ago, and are thus the
earliest ancestors of modern day vertebrates. These sac-like filter feeders produce Ecteinascidin, a
compound that blocks DNA transcription and may have potentialfor treating breast cancer [70].
3.2. Micro-organisms
Microorganisms represent the greatest percentage of undescribed marine species [71] and
include diverse organisms such as bacteria, viruses, microalgae, and fungi and possess a variety of
morphological, ecological, and physiological characteristics [72]. Marine microorganisms represent a
significant untapped source of novel bioactive complexes and compounds, presenting the prospect of
producing novel compounds that may contribute significantly to drug development [73]. Marine
hydrobionts and microorganisms are promising sources of highly specific nucleases and phosphatases.
Ca2+ and Mg2+ -dependent DNases of marine origin preferentially cleave double-stranded DNA and
polydeoxynucleotides, whereas single-stranded substrates are resistant to their action. This allows a new
method of detecting single nucleotide substitution in gene analysis. With the help of molecular and
biotechnological techniques, studies have demonstrated that many surface associated bacteria produce
antibiotic substances. The cyclic decapeptide antibiotic, loloatin B, is obtained from a Bacillus species
isolated from a unidentified tube marine worm (Loloata Island,Papua New Guinea) and used against
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methicillin-resistant Staphylococcus aureus. Another novel antibiotic, thiomarinol, was produced from a
marine bacterium Alteromonas rava [74]. Enzymespromising for medical applications, α-N-
acetylgalactosaminidase and thermolabile α-galactosidase, have been isolated from marine bacteria of
Arenibacter latericius and of Pseudoalteromonas spp., respectively [75]. It has been shown that α-N-
acetylgalactosaminidase isolated from Arenibacter latericius is capable of inactivating blood type
specificity of human A-erythrocytes [76], whereas α-galactosidase is able to inactivate the group
specificity B of human red blood cells and interrupt the adhesion of the pathogenic bacterium
Corinebacterium diphtheria to buccal epithelium cells [75].
Antimicrobial metabolites produced by marine bacteria have been found to be applicable in
medicine [76]. Compounds derived from marine fungi, including Sorbicillacton A, also show potential
for therapeutic uses [77]. Peng et al revealed that antioxidant compounds such as acremonin from
Acremonium species, xanthenes derivative from Wardomyees anomalus, and 4,5,6-trihydroxy
methyphthalide from Epioeeum species prevent oxidative damage linked to dementia, atherosclerosis,
and cancer [78]. In addition, marine microalgae produce some highly bioactive compounds such as fatty
acids, protein, antioxidant pigments and polysaccharides that make them attractive for demand by the
pharmaceutical and medical industry [79]. However, despite this only a few of them, such as β-carotene
and astaxanthin, have been produced at industrial scale [80], due to their low production in native
microalgae and the difficulty in isolating them by economically feasible means [80]. The great
biomedical and biotechnological potential also showed marine viruses but yet the exploration of the
marine virome, and the associated gene and protein pool, is only beginning [82].
The marine environment in rich in macro- and micro-organisms. The development and
utilization of their genes, secondary metabolites, enzymes, and other active substances is a major area of
medicine. Marine organisms are not fully explored and the works are reviewed here as baseline further
research in this field.
IV. MARINE-DERIVED BIOLOGICAL MACROMOLECULES AS BIOMATERIAL
Marine biomaterials have advantages ranging from availability to biocompatibility, and are
known for their ecological safety and the possibility of producing enzymatically modified derivatives for
various purposes and applications [83]. Biomaterials based on marine macromolecules are categorized
into subgroups according to source, primarily polysaccharide-based biomaterials and protein-based
biomaterials.
Polysaccharide-based biomaterials are an emerging class in biomedical fields such as tissue
regeneration, especially cartilage, drug delivery devices, and gel entrapment systems for cell
immobilization [84]. Polysaccharides are macromolecules with varied biological properties, from a
broad array ofnatural sources [85]. Algae are the main producers of marine polysaccharides, but they
can also be obtained from animal sources and microorganisms [86]. Many polysaccharides have been
extracted from marine organisms, the most representative being chitin and its derivative chitosan,
alginates, carrageenans, and agar.
Alginate is a polysaccharide extracted from brown seaweed, including Laminaria hyperborea,
Laminaria digitata, Laminaria japonica, Ascophyllum nodosum, and Macrocystis pyrifera [87]. It is
composed of a sequence of two (1→4)-linked α-l-guluronate (G) and β-d-mannuronate (M) monomers.
Alginate is biocompatible, with low toxicity and high bioavailability, giving it wide biomedical
applicability [85]. Carrageenans are anionic polysaccharides of marine origin. Carrageenans are
composed of D-galactose backbone and fill spaces between the cellulosic structures of seaweed [53].
The major sources of industrially relevant κ-carrageenan, ι-carrageenan and λ-carrageenan are red
seaweed of Kappaphycusalvarezii, Eucheumaspinosum, and Gigartina species [88]. The use of
carrageenan as an excipient in the pharmaceutical industry is common, thus reports on its applications,
characteristics, and functions are frequent [89]. Agar (or agar-agar) is an unbranched polysaccharide
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obtained from the cell membranes of red algae. Chemically, it is constituted of galactose sugar
molecules and is the primary structural support for the algae cell walls [90]. In food industry agar
comonly used as gelatin and thickener, in microbiology as a gel for electrophoresis [84]. In
pharmaceuticals application agar is used as biofilms, suppositories, anticoagulants and as ingredients in
tablets [61].
Marine animals are also a source of polysaccharides. The primary component of the exoskeleton
of arthropods and crustaceans such as crab, shrimp, and lobster is chitin polysaccharide [85]. Chitin is
not water soluble, and is almost solely used as a raw material for the production of chitosan and other
derivatives. Chitosan is a linear polysaccharide, one of the most numerous natural polymers of our
ecosystem [69]. Chitosan is frequently used in medicine due to its biological properties, including
antimicrobial, hemostatic, and antitumor activity; its acceleration of the wound healing process;
applicability in tissue engineering scaffolds; and potential for drug delivery [91].
The mentioned polysaccharides represent the most abundant polymers of marine origin. In
addition, polysaccharides such as fucoidans, ulvans, and hyaluronans are commonly produced from
marine species and can be material for biomedical applications [92].
Proteins are important marine bioactive molecules that exhibit a range of molecular mechanisms
and present promise for medical, pharmaceutical, and biotechnological applications. Over the past two
decades, significant progress has been made in isolation of proteins from marine organisms for potential
use in biomaterials [42]. Collagens are among the most abundant. Collagens are high molecular weight
proteins that play primarily a structural role in both invertebrates and vertebrates, and differ according
with their organization in tissues [93]. Marine collagen is a fibrous protein extracted from species such
as the marine sponge Chondrosia reniformis Nardo [94]; rhizostomous jellyfish [95]; fish waste material
including skin, bone, and fins [96]; the paper nautilus [96]; muscle and skin of marine mammals [97];
cuttlefish [98]; squid skin [99]; and Sebastes mentella [99]. Preliminary animal and clinical studies have
identified medicinal properties of collagen [93].
The shells of mollusks are composed mainly of calcium carbonate, with small amounts of matrix
proteins and, for more than 50 years, have attracted attention for their unique mechanical and biological
properties [100]. Skeletal proteins in marine organisms are present as complex mixtures within organic
matrices. The organic matrices of marine calcifiers, for example, are potentially an untapped source of
skeletal proteins [101,102]. It has been hypothesized that some of these proteins with human
physiological activity can accelerate laboratory-based attempts at bone morphogenesis and increase
bone volume with efficacy equivalent to currently used recombinant proteins [102]. Marine peptides as
specific protein fragments have potential physiological functions [103]. These peptides have been
obtained from algae, fish, mollusks, crustaceans, crab and marine bacteria and fungi. Bioactive marine
peptides, due to their structural properties, amino acid composition, and genetic sequences, have been
shown to display bioactivity such including anti-tumor, antiviral, anticoagulant, antioxidant, and
immunoinflammatory effects [104, 25].
V. CHALLENGES
Despite the enormous biotechnological potential of marine organisms, there are still limitations
for their fast and successful developed into marketed products. Major obstacles to the development of
these products are associated with lack of taxonomic knowledge of marine species, collecting methods,
and isolation and sustainable production of the pure bioactive from marine organisms, as well as
problems linked to supply, technical, and commercial issues.
A critical point in the process of pharmaceutical development from marine organisms is
obtaining permanent availability of sufficient quantities of organisms and compounds without causing
environmental harm. Only if supply can be addressed in an economically and ecologically
practicablefashion, will development and marketing of marine-derived drugs be feasible [105, 106].
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Obtaining resources from marine organisms and exploiting them on a large scale is a challenge. In the
recent years isolation and structure elucidation technology has advanced enormously, nevertheless when
process coupled to a biological assay it can sometimes takes weeks or months. This is simply too slow
to compete with the screening of pure compounds with known structures [107]. Additionally, the
synthesis of a bioactive natural compound must be supported by a correct identification of the
compound isolated from the biological source [7]. Living organisms are difficult to find in the broad
expanse of the ocean, and they often occur in low quantities. The majority of pharmaceutically
applicable marine organisms, especially microorganisms, are impossible to culture of maintain under
artificial conditions for long periods [108]: (i) Laboratory culture may demolish the interactions between
organisms that occur in natural condition; (ii) Marine microorganisms may be unable to grow on the
substrate or combination of substrates provided; (iii) Virus infection may affect or prevent growth in
culture; and (iv) The high concentrations of substrate required for detectable growth in the laboratory
may be toxic, particularly for marine bacteria [108]. Hence, a better understanding of the living
conditions of marine organisms in the natural environment is needed to develop methods for culture and
maintenance and the production of metabolites.
The lack of taxonomic knowledge of marine species, with a still substantial number of
unidentified species and strains, is also a major challenge to marine product development. Incorrect
classification of a species may compromise development of a drug treatment, not only because it is
impossible to reproduce the isolation of a bioactive extract and/or metabolite, but also because it can
mislead the dereplication process by which the bioactives are identified.
Approaches to marine macro-organisms and micro-organisms classification are different. For the
majority of marine macro-organisms, taxonomic knowledge is still insufficient to enable unambiguous
species classification [109]. Macro-invertebrates are especially challenging, not only due the fact that
there are still many undescribed species, but because many related species must be distinguished based
on subtle morphological characteristics [110].
Several problems are related to supply and market issues. The first is associated with the
variability of the organism itself. Wild marine organisms collected for bioprospecting are exposed to
environmental variations, as well as changes at the community level, which may significantly affect
their chemical ecology [111]. The same species individuals sampled in the different parts or time frames
may show the diverse chemical composition [112] and, therefore, fail to guarantee the supply of a target
metabolite. This may also be a potential caveat for the initial detection of bioactive metabolites, as
environmental and individual variability in the chemical composition of target organisms may bias
bioprospecting [113]. Also associated with replicability issues is the potential loss of the source through
extinction of target species.
Market issues are relevant and often disregarded in natural product development programs.
Important points for successful development of drugs from marine organisms include (i) potential
industry applications and market demand; (ii) the target price of the final bioactive; (iii) desired
formulation and administration route; (iv) manufacturing process and sustainability, and (v) how the
product can reach the market value chain [7].
It is evident that the supply problem is at the center of the constraints to marine therapeutic drug
manufacture, and is usually strongest in the early stages of development.
VI. CONCLUSION
The recent advances in their development, approval, and use demonstrate the huge potential of
marine natural products. Marine products produce toxins and secondary metabolites with insecticidal,
nematocidal, herbicidal, and fungicidal actions and present enormous opportunity for the development
of consumer products. Some of marine-derived compounds have produced approved drugs, mostly in
cancer treatment, but also for virus and pain reduction. The advent of marine-derived biomaterials
International Journal of Modern Trends in Engineering and Research (IJMTER) Volume: 5, Issue: 03, [March– 2018]ISSN (Online):2349–9745 ; ISSN (Print):2393-8161
@IJMTER-2018, All rights Reserved 219
represents a new horizon in biomedical science. Although a variety of molecules and materials from
marine organisms exhibit useful characteristics and properties, they represent only a small fraction of
compounds that have been patented for medical applications, mainly because of many challenges
associate with their discovery and exploitation. Therefore, it is necessary to focus on biodiversity access,
sustainable supply, and technical support to increase development and availability of natural marine-
derived pharmaceuticals.
VII. ACKNOWLEDGEMENTS
The study was financially supported by CAS President’s International Fellowship for
Postdoctoral Researchers (2017PB0060), National Natural Science Foundation of China (21676286),
and Primary Research Development Plan of Shandong Province (2016GSF121006) and also by the
Ministry of Education, Youth and Sports of the Czech Republic - projects CENAKVA (No.
CZ.1.05/2.1.00/01.0024) and CENAKVA II (No. LO1205 under the NPU I program). The Lucidus
Consultancy, UK is gratefully acknowledged for English correction.
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