1. Introduction
Marine ecosystem is the largest ecosystem in this world. It accounts 70% of the planet Earth. It consists of different
geographical zones (Fig 1). Each zone in
marine ecosystem has different environment
and this environment effects differently on
Oceans
the biotic and abiotic factors in it. Due to this
Salt
divers environment living organism produce
Esturies
Marshes
many industrially and medically important
compounds in the form of secondary
metabolites.
Micro-Organisms produce special organic
Intertidal
Lagoons
compounds that have no function in growth
zones
and development of organisms. These organic
Marine
compounds are secondary metabolites. These
are products of natural selection that are
produces in response to environment (Julijana
Sea
Mangrove
Ivanis evic et al, 2010) to bring about
Floor
biodiversity. Some of these secondary
metabolites when extracted from organisms
Deep
Coral
have important industrial and medical uses.
Sea
Reef
Secondary metabolites extracted from
Figure 1: Different Components of Marine Ecosystem
marine sources have lot of potential in
medical applications. Some very significant
bioactive compounds have been extracted from marine sources (Table 1).
Compound
Aureoverticillactam
Polihalogenated indoles
Lipopeptides microcoline B
Pyrroles
Methylicosadienoic acid
Source
Streptomyces aureoverticillatus
Rhodophyllis mambranacea
Cayano Bacteria
Cephalosporium acremonium
Cambastela axinellida
Activity
Anti-tumor
Anti-fungal
Inhibit cell division
Anti-Bacterial
Larvicidal
Reference
Mitchell et al. 2004
Brenman & Erickson, 1978
Takamatsu S et al, 2004
K. Manimegalai1 et al, 2013
(Joseph elvin & A. P. Lipton, 2004)
Table 1: Marine isolated Secondary metabolites and there sources.
2. Marine Sources of Secondary Metabolites
Marine ecosystem has wide range of biodiversity. Each organism has different characteristics and it produce
different secondary metabolites in response to its environment. Following are some of the marine sources for
secondary metabolite production (Francesco Pietra, 1997):
1. Marine Isolated Bacteria
a. Actinomycetes
b. Cyano-Bacteria
c. Archae-Bacteria
2. Euglenoids
3. Diatoms
4. Diano-flagellets
5. Marine Fungi
6. Green Microalgae
7. Sponges
8. Many more
These are some of the potential sources of marine secondary metabolites because of their anti-fungal, anti-bacterial
(K. Manimegalai1 et al, 2013), anti-tumor, anti-oxidant and anti-inflammatory (Bhimba B Valentin et al, 2011)
activities. We will discuss only major three classes.
3. Secondary Metabolites from Marine Sponges
Sponges are structurally diverse and biologically active (Julijana Ivanis evic et al, 2010) group of invertebrates in
marine ecosystem. They are sessile organisms that are present on the rocks or at the sea bed. Studies have showed
the sponges are potent producer of secondary metabolites that may be of great industrial importance. Following are
some of the industrially useful characteristic of sponges due to secondary metabolites are explained:
3.1. Anti-Bacterial
In a research it has been demonstrated that secondary metabolites produced by Dendrillu nigre, Axinellu donnani
and Clathria gorgonoides marine sponges have bactericidal activity (Joseph elvin & A. P. Lipton, 2004). These sponges
show high bactericidal activity against B. subtilis, P. aregenusa, E. coli and many other bacterial species.
In another study it has been showed that Aplysina species i.e. Aplysina aerophoba and A. cavernicola produce
aerophobin-2 and aplysinamisin-1 as brominated isoxazoline alkaloids (Düsseldorf & März 2009) which show great
anti-bacterial activity.
3.2. Larvicidal Effects
It has been seen that secondary metabolites produced by Clathria gorgonoides (Joseph elvin & A. P. Lipton, 2004)
kill the larvae of mosquitoes. It may have great role in the control of malaria. Dendrillu nigre, and Axinellu donnani
also show larvicidal activity.
It was also be seen that Methylicosadienoic acid produce by Cambastela axinellida (Joseph elvin & A. P. Lipton, 2004)
kills the larvae of beet army worm and corn root worm.
3.3. Ichthyotoxicity
Secondary metabolites produced by certain marine organism protect the host organisms from predator’s i.e. antipredatory effects. D. niger produce large amount of toxins (Joseph elvin & A. P. Lipton, 2004) to prevent the
predators. Two classes of terpenoid toxins are produced by sporangia sp. (Joseph elvin & A. P. Lipton, 2004).
3.4. Anti-Fouling activity
One of the major problem faced by man-made marine infrastructure is biofouling. This biofouling interferes with the
structure and cause the malfunction. Studies showed that sponges such as D. niger, Hyrtios sp., Aplisnella sp. and
Xestospongia ashmorica etc (Joseph elvin & A. P. Lipton, 2004) show anti-bacterial, brineshrimp cytoyoxity and
larvicidal activity.
3.5. Anti-tumor Activity
Dysidea avara, is a Mediterranean sublittoral sponges that produce avarol and 5′-monoacetylavarol (Sonia De Caralt
et al, 2013) at high level during spring – early summer. These secondary metabolite have anti-leukemia and anticancer activity
4. Secondary metabolites from Marine algae
Secondary metabolites are the compounds produced during algal life cycle which don’t play a direct role in algal
growth but are required for the betterment of algal life styles. These compound mostly play a role for the defense
of the algal organism. The pathways for production of these secondary metabolites can be exploited by us as they
play anti-microbial, anti-fungal, anti-parasitic, anti-tumor, anti-proliferative, anti-inflammatory and anti-biotic
effects.
4.1. Halogenated compounds from marine algae
These are the compounds which contain highly active and functional halogen group (Cl, Br, F and Iodine). These
compounds include peptides, indoles, polyketides, acetogenins and phenol.
4.1.1.
Brown Algae
Meroditerpenoid fallachromenoic acid, a terpene obtained from brown algae is reported to have anti-tumor effects
against P388 Murine Leukemia cell line. This particular compound is separated from Sargassum fallax.
4.1.2. Red Algae
C15 acetogenin en-ynes separated from Laurencia glandulifera have cytotoxic effects against colorectal adenocarcinoma (HT-29), mammary adenocarcinoma (MCF-7) and prostate adenocarcinoma (PC-3).(M.T. Cabrita et al,
2010)
4.2. Metallothioniens
Metallothioneins are the cysteine rich low molecular weight proteins that play a detoxification role in organisms by
binding to heavy metals through their Thiol group.In algae class 3 of metallothionein is reported to exist.one such
protein has been successfully extracted from Phaeodactylum tricornutum, a marine diatoms. This proteins induces
tolerance against high toxic levels of cadmium. (E torres et al 1997).
4.3. Biogenic Anti-fouling agents
Solid metallic surfaces when exposed to seas water undergo many changes because of physical, chemical and
biological activity. Marine living organism like barnacles, oysters, tunicates, bryozoan and microbial slimes are among
the leading causative agents. Many macro algae that live in euphotic zone are reported to produce fatty acids,
lippopeptides, amides, alkaloids, pyroles, steroids and lactones. These compounds are immiscible in water and
remain in a layered form without providing any environmental hazard.(Punyasloke B and Phillip C wright, 2004)
4.4. Anti-bacterial agents
Some metabolites produced by marine algae have allelopathic effects i.e they affect the growth of other organisms
in surrounding. One such compound has been isolated from red algae species Delisea pulchra. Chemically this
compound falls under the category of furanones and is reported to inhibit growth of 119 marine bacterial strains.
(Ria Meximilien et al, 1998).
4.5. Anti-tumour agents
The chemical compounds known as Fucoidans (marine algal polysaccharide) obtained from Sargassum
thunbergii has been reported to have anti-tumor activities against Ehlrich ascities carcinoma. The functional group
of this compound is L-fucan sulphate. It is co-activator of reticulo-endothelial system and potent activator of
macrophages. (Xue, Meilan, et al, 2012)
4.6. Anti-inflammatory agents
Water soluble extracts that are crude in nature obtained from brown alga Turbinaria ornate acts an anti-oxidant and
anti-inflammatory. Similarly pheophytin obtained from edible green algae Enteromorpha prolifera also act as antiinflammatory. (Yasuji Okai, et al 1997) (subash anthani et al 2004)
5. Secondary metabolites from Marine Bacteria
Bacterial metabolism can be classified into three major categories: the kind of energy used for growth, the carbon
source, and the electron donors used for growth. Pathogenic bacteria are capable of exhibiting various types of
metabolism. Metabolites, the intermediates and products of metabolism, are typically characterized by small
molecules with various functions. Metabolites can be categorized into both primary and secondary metabolites.
These metabolites can be used in industrial microbiology to obtain amino acids, develop vaccines and antibiotics,
and isolate chemicals necessary for organic synthesis.
5.1. Production and uses
Secondary metabolites are typically organic compounds produced through the modification of primary metabolite
synthases. Secondary metabolites do not play a role in growth, development, and reproduction like primary
metabolites do, and are typically formed during the end or near the stationary phase of growth. Many of the
identified secondary metabolites have a role in ecological function, including defense mechanism(s), by serving as
antibiotics and by producing pigments. Examples of secondary metabolites with importance in industrial
microbiology include atropine and antibiotics such as erythromycin and bacitracin. Atropine, derived from various
plants, is a secondary metabolite with important use in the clinic. Atropine is a competitive antagonist for
acetylcholine receptors, specifically those of the muscarinic type, which can be used in the treatment of bradycardia.
Antibiotics such as erythromycin and bacitracin are also considered to be secondary metabolites. Erythromycin,
derived from Saccharopolyspora erythraea, is a commonly used antibiotic with a wide antimicrobial spectrum. It is
mass produced and commonly administered orally. Lastly, another example of an antibiotic which is classified as a
secondary metabolite is bacitracin. Bacitracin, derived from organisms classified under Bacillus subtilis, is an
antibiotic commonly used a topical drug. Bacitracin is synthesized in nature as a non-ribosomal peptide synthetize
that can synthesize peptides; however, it is used in the clinic as an antibiotic.
5.2. Erythromycin Tablets
Erythromycin is an example of a secondary metabolite used as an antibiotic and mass produced within industrial
microbiology.Since the discovery of penicillin in 1928 (Fleming, 1929), intensive studies, mainly on soil-derived
bacteria and fungi, demonstrated that microorganisms are a rich source of structurally unique bioactive substances
(Fenical, 1993). The increasing need for new antimicrobial agents able to control emerging diseases or resistant
strains of microorganisms inspired a growing number of research groups to explore the oceans for new bioactive
compounds. Throughout the years, extensive screening programs were developed worldwide and great efforts have
been devoted aiming of the isolation of new metabolites from marine microorganisms.
5.3. Other drugs
Marine microorganisms are often taxonomically unique, which makes them interesting as potential sources of new
drug leads. One of the major areas of research on marine natural products is devoted to the discovery of new anticancer drugs. In 1997, a novel depsipeptide named thiocoraline was isolated from the mycelial extract of the
bacterium Micromonospora marina associated with a marine soft coral in the Indian Ocean. Thiocoraline inhibited
DNA polymerase-α and is currently in preclinical phase by the pharmaceutical company PharmaMar (Romero et al.,
1997; Newman and Cragg, 2004).
Marine-derived bacteria constitute a promising source of unique metabolites with considerable pharmaceutical and
therapeutically potential. Common biological assays usually focus on antimicrobial and cytotoxic activities as
demonstrated throughout the literature. Whereas more effective and safe drugs in the field on infectious diseases
and cancer are certainly needed, many other pharmacologically active compounds may be overlooked. Thus, it is
suggested to broaden biological screens for the discovery of exceptional and rarely investigated biological activities,
which may be important for the therapy of chronic diseases. Examples mentioned in this review include the potent
PTP1B inhibiting activity of aquastatin A (101) which may be a promising therapeutic agent for treatment of type 2
diabetes and obesity, as well as the carcinogen metabolizing enzymes modulatory activity of chromanone A (100),
which could be helpful in preventing the initiation stage of carcinogenesis. Such activities trigger the continued
interest in marine microbial natural products and reflect the need for more intensive investigation of their chemical
and pharmacological property.
5.4. Prodiginines
Red-pigmented prodigiosin compounds were first isolated from the ubiquitous bacterium Serratia marcescens and
identified as secondary metabolites. The common aromatic chemical structure of these pigmented compounds was
first named prodiginine by Gerber [6] (Figure 1). Prodigiosin was the first prodiginine for which the chemical structure
was determined [7]. The name “prodigiosin” has been attributed to the isolation of prodigiosin from Bacillus
prodigiosus bacterium (later renamed Serratia marcescens) [8], which was historically famed for the mysterious
“bleeding bread” report [9, 10]. Prodiginines share a common pyrrolyldipyrromethene core structure and have a
wide variety of biological properties, including antibacterial, antifungal, antimalarial, antibiotic, immunosuppressive,
and anticancer activities [9, 11]. Such properties potentially make them one of the most powerful research tools in
the past decade.
6. Secondary metabolites from marine fungi
Fungi produce a multitude of bioactive compounds. The increasing number of fungal genome sequences,
demonstrate the biosynthetic potential of fungi. The genes required for the biosynthesis of secondary metabolite
are clustered.
6.1. Endophytic fungi
Endophytic fungi form association with the plants and it alters the mechanisms of host and induce the production
of secondary metabolites. The symbiotic relation helps the fungi to get nutrition while the plants use the fungi for
defense (Samual et al, 2011).
6.2. Anti-microbial agents
Triazole an antimicrobial compound, obtained from sponge associated marine fungi. This compound is used for the
treatment of skin infection. Trizole is also used nowadays as agent for wound dressing to prevent bacterial and fungal
infection (Amber et al, 2004).
6.3. Anti-tumor agents:
The extracts obtained from Penicillium brevicompactum .Are reported to have cyto-toxic effects against six tumor
cell lines Marine fungi produce novel compounds because of their ability to survive under condition like high salinity,
temperature and high pressure.(samual et al, 2011).
6.4. Anti-inflammatory
Pencillinolide is anti-inflammatory metabolite that is isolated from the penicillin species.(Perry et al,2013).
6.5. Novel compounds
A new sesquiterpenoid compound, was isolated from the culture of the mangrove fungus. Microsphaeropsis sp was
used to isolate a sesquiterpenoid compound, that microsphaeropsisin A (Shao C et al, 2009).
Halovirs are the peptides (A-E) that are isolated from the fungus scytalidium. It has the anti-viral activity and used to
prevent and inhibit the HSV infection. (herspes simplex virus) (John et al, 2001).
6.6. Anti-Biotic
The antibiotic, paecilospirone is a new compound produced by cultured marine fungus, when a marine bacterium,
strain CNJ-328, was co-cultured in fungal fermentation. The fungus, isolated from the surface of the brown alga
Rosenvingea sp. (Mercedes et al, 2001).
6.7. Anti-Algal agents
Anti-algal activities shown by the endophytic fungus of genus Geniculosporium was isolated from Teucrium
scorodonia. The extract of this isolate exhibited anti-algal activities. Coniothyrium sp. produce a phenoxyphenyl ether
named coniothyen, that exhibit anti algal and anti-bacterial activities. (Peter et al, 2007).
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