Applications of natural marine materials: Opportunities ......new therapeutic molecules has given rise to a vast nu mber of studies in marine fish, invertebrates and microbes [2]

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

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 211

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



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



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.



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



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



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



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].



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



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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Applications of natural marine materials: Opportunities ......new therapeutic molecules has given rise to a vast nu mber of studies in marine fish, invertebrates and microbes [2]