Review on bioactive potential of marine microbes

There is a need for new drugs especially novel antibiotics, anticancer compound, antibiotic against multi drug-resistant bacteria. The discovery and development of new drugs from marine microbes played a significant role over the last few decades. The world oceans comprise a rich diversity of microbial life with current estimates reaching over a million different species. Marine microbes are important from both ecological and biotechnological point of view. Marine microbial bioactive compounds have attracted increasing attention from microbiologists, taxonomists, ecologists, agronomists, chemists and evolutionary biologists.


INTRODUCTION
Marine microbes having immense genetic and biochemical diversity have become a rich source of novel effective drugs.It is surprising to find that many bioactive compounds, reported from marine invertebrates are produced by their microbial symbionts.Competition among microbes for space and nutrients in the marine environment is a driving force behind the production of such precious antibiotics and other useful pharmaceuticals.Interestingly, microorganisms associated with marine invertebrates are proved as valuable candidates for drug discovery program.
Like bacteria, marine fungi are also reported to be potential source of bioactive substances.For example, sorbicilactone-A, a novel type alkaloid was reported from sponge (Ircinia fasciculata) associated fungus, Penicillium chrysogenum.This compound showed therapeutic potential in human trials.Polyketide synthases (PKSs) are a class of enzymes that are involved in the biosynthesis of secondary metabolites like erythromycin (Lamela et al., 1989;Parkes et al., 1994;Hentschel et al., 2003).
Since the discovery of penicillin in 1929, a number of natural products are reported to have biological activities that are in use today as antibiotics, antitumour agents and agrochemicals (Davidson et al., 2001).The development of the fungal metabolite, Mevinolin for the treatment of high serum cholesterol and the bacterial metabolite FK-506 as an immunosuppressant illustrate the vast natural diversity of microbial natural products (Faulkner, 1992).In spite of such successes in drug discovery from terrestrial microorganisms, marine microorganisms have received only very little attention on account of the non-culturability of the majority of marine bacteria (Gaino and Sara, 1994).
Marine toxins such as tetrodotoxin and saxitoxin are potent and specific sodium channel blockers and pharmacological studies on these toxins have played a major role in developing the concept of sodium channels in general and membrane channels in particular (Gustafson et al., 1989).There is an increasing evidence that several anti-cancer compounds isolated from sponges or other marine invertebrates are actually produced by bacteria associated with these invertebrates.Bryostatins were initially isolated from a bryozoan, Bugula neritina.Putative type 1 polyketide synthase genes had been found in bacteria from colonies of B. neritina producing bryostatin and these genes were absent in bacteria associated with colonies of B. neritina that did not produce bryostatin (Holst et al., 1994).Dolastatin isolated from the Indian Ocean seahare Dolabella auricularia has also been isolated from marine cyanobacteria (Hugenholtz and Pace, 1996) like Lyngbya majuscule (Ireland, 1993).

MARINE BACTERIA AND ACTINOMYCETES
About 20% of bacteria from marine sponge and coral in different coastal areas of the China Sea showed positive antimicrobial activity (Zheng et al., 2005).In the study of Li et al. (2007), some bacteria were isolated from the sponges Stelletta tenuis, Halichondria rugosa and Dysidea avara which showed pronounced broadspectrum of antimicrobial activities and enzymatic potentials.Brammavidhya and Usharani (2013) extracted and optimized the bioactive compound and it act against the human pathogen which was isolated from Hyattella cribriformis associated Bacillus cereus SBS02.
Bacillamides have been proven to inhibit the growth of red-tide algae such as Cochlodinium polykrikoides (Jeong et al., 2003).A novel thiazole alkaloid, neobacillamide A together with a known related one, bacillamide C were isolated from Bacillus vallismortis C89 associated with the South China Sea sponge, Dysidea avara (Yu et al., 2009).Studies made by the scientists at the Scripps Institute of Oceanography showed that marine bacteria are capable of producing unusual bioactive compounds that are not observed in terrestrial sources (Fenical, 1993;Fenical and Jensen, 1993).Pandey et al. (2013) studied the diversity of betaglucosidase inhibitors producing marine bacteria.They observed that the marine sponge Aka coralliphaga associated bacteria had produced beta-glucosidase inhibitors as compared to other associated microbes.Mithun and Rama (2012) isolated and identified Micrococcus luteus sp.from marine soil samples collected from Bay of Bengal coast of Machilipatnam, Krishna district, Andhra, India.This strain showed promising results against cancer cell line namely HCT 15 and MES-SA.
Thermo-stable proteases, lipases, esterases and starch and xylan degrading enzymes have been actively sought and in many cases are found in bacterial and archaeal hyper thermophilic marine microorganisms (Bertoldo and Antranikian, 2002).An unusual Gram-positive bacterium from deep-sea sediment produced a series of natural products, for example macrolactin A-F of an unprecedented C 24 linear acetogen origin (Gustafson, 1989).The major metabolite, macrolactin A inhibited B16-F10 murine melanoma cells in in vitro assays, showing significant inhibition of mammalian Herpes simplex virus (type I and II) and protecting T lymphocytes against human immunodeficiency virus (HIV) replication (Carte, 1996).
On the other hand, a microbial metabolite obtained from Alteromonas spp.isolated from the tissues of sponge had anti HIV activity due to the production of reverse transcriptase inhibitor.Some Vibrio species have been found to produce a variety of extra cellular proteases.Vibrio alginolyticus produced six proteases including an unusual detergent-resistant, alkaline serine exoprotease, this marine bacterium also produced collagenase, an enzyme with a variety of industrial and commercial applications, including the dispersion of cells in tissue culture studies (Graham et al., 1980;Osama and Koga, 1995).Bioactive compound, Cis-sativenediol extracted from Aeromonas sp and Rhodopseudomonas sp. which was collected from coastal water of Thoothukudi, Thiruchendur and Kanyakumarai Tamil Nadu, India act against Enterobacter aerogenes, Pseudomonas aeruginosa, Streptococcus mutans, Staphylococcus epidermidis and S. aureus (Ashadevi et al., 2011).
Seven new prenylated indole diketopiperazine alkaloids, including spirotryprostatins derivatives of fumitremorgin B, and 13-oxoverruculogen, have been isolated from the holothurian-derived fungus Aspergillus fumigatus.These compounds showed anticancer activity to four cancer cell lines, MOLT-4, A549, HL-60 and BEL-7420 (Wang et al., 2008).Lasiodiplodin, which could inhibit the in vitro growth of S. aureus, Bacillus subtilis and Fusarium oxysporum, were isolated from the mycelium extracts of an endophytic fungus obtained from the brown algae species collected from Zhanjiang sea area by Yang et al. (2006).
When compared with the small molecular metabolites of marine microbial symbionts, the investigation of pharmaceutical big molecule metabolites is rare.The gene cloning, purification, properties, kinetics and antifungal activity of chitinase from marine Streptomyces spp.DA11 associated with the South China Sea sponge Craniella australiensis were investigated by Han et al. (2009).
Association of fungi with marine animals ranges from saprotrophic, symbiotic to parasitic.Saprotrophic fungi have been isolated from the surface, guts and fluids of holothurians or the sea cucumbers (Pivkin, 2000).

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Several fungi isolated from invertebrates have been found to produce interesting secondary metabolites.A novel group of platelet activating factor (PAF) antagonists, phomactins A, B, B1 and B2 were isolated from culture broth of Phoma isolated from the shell of crab Chinoecetes opilio collected from the coast of Fukuii, Japan (Sugano et al., 1991).Two lipophilic tri peptides from Penicillium fellutanum live inside the gastrointestine of a marine fish and three quinazoline derivatives from Aspergillus fumigatus from gastrointestinal tract of the fish, Pseudolabrus japonicas from the coast of Japan (Kobayashi and Ishibashi, 1993).An endolithic fungus Ostracoblabe implexa living inside the shells of rock oyster Crassostrea cucullata from the coast of Goa was reported (Raghukumar and Lande, 1988).Fungi belonging to the class of Trichomycetes are found in the guts of marine arthropods, isopods, decapods and amphipods in a symbiotic association (Misra and Lichtwardt, 2000).Endolithic fungi in coral skeleton are common (Alsumard et al., 1995;Ravindran et al., 2001;Golubic et al., 2005).
A basidiomycetous yeast Cryptococcus spp.associated with Pocillopora damicornis coral skeleton was shown to produce a transient cryoprotective effect, selectively enhancing the survival of skeletogenic cell types (Coulon et al., 2004) -which gave some detailed characteristic of this cryoprotective effect, some values would be very interesting.Colecobasidium species was isolated from necrotic patches in several massive corals in the Andamans (Raghukumar and Raghukumar, 1991).Biological activities of microbes are mainly focused in the areas of antibiotic and anticancer properties, but other selective activities include cell cycle inhibition, antagonism of platelet activating factor, antiviral activity, neuritogenic activity, phosphatase inhibition and kinase inhibition and radical scavenging activities are less attended (Bugni and Ireland, 2004).Among the eukaryotic microscopic fungi, the inhibitory compounds capability of imperfect fungi, the ascomycetes and several other filamentous and endophytic fungal species are the most significant (Shearer and Maivan, 1988).Several compounds that inhibit the growth of a large spectrum of saprophytic and phytopathogenic fungi were isolated from basidiomycetes (Anke, 1989(Anke, , 1995)).
A marine-derived Penicillium chrysogenum isolated from the sponge, Ircinia fasciculate produced a sorbicillin derived alkaloid sorbicillacton A (Bringmann et al., 2003) which showed selective cyctostatic activity against lympho blasts and was able to protect human T cells against HIV-1.Preclinical evaluation of this compound has recently been initiated.Many of these fungi have novel carbon skeletons thus providing further evidence of the potential of marine-derived fungi (Proksch et al., 2003).
The first crystalline fungal product obtained from Penicillium glaucoma was chemically myco phenolic acid and it was discovered in 1896 (Berdy, 2005).Microbial secondary metabolites regulate growth processes, replications, and/or exhibited some kind of regulatory, inhibitory or stimulatory responses in prokaryotic and eukaryotic cells even at a minimal concentration.Marinederived isolate of Aspergillus versicolor (MST-MF495) yielded many known fungal metabolites like sterigmatocystin, violaceol I, violaceol II, diorcinol, (-) cyclopenol and viridicatol, along with a new alkaloid, cottoquinazoline A , and two new cyclopentapeptides, cotteslosins A and B (Fremlin et al., 2009).Moreover, the great practical and historical importance of beta-lactams (penicillins, cephalosporins), the cyclosporin, and various statins (mevinolin, compactin, lovastatin, pravastatin, atrovastatin) which are all fungus derived compounds are well known (Donadio et al., 2002).
Several compounds from marine fungi have been screened for antifungal activities, and a number of compounds have been characterized with regard to their inhibitory activities and chemical structures.There has been a sharp increase in fungal infections among patients suffering from HIV, receiving cancer and immune-therapy (Anaissie, 1992;Li et al., 1998;Barrett, 2002).Recent research showed that compounds like Hypoxysordarin, a new sordarin derivative, isolated from the facultative marine fungus Hypoxylon croceum are promising.
Terrestrial fungi produce a variety of chemically diverse natural compounds with interesting biological activities.Until recently, only modest attention has been given to metabolites from marine (marine derived) fungi.To date, a number of new compounds from marine fungi have been described and reviewed (Biabani and Laatsch, 1998;Faulkner, 2000Faulkner, , 1992;;Jensen and Fenical, 2002;Proksch et al., 2003;Bugni and Ireland, 2004).These documented discoveries clearly showed that marine fungi are of high profile source of structurally unique and biologically active natural compounds as compared to terrestrial fungi.Fungi associated with sponges are the single most potential source of new marine fungal compounds and display diverse biological activities (Jensen and Fenical, 2000;Bugni and Ireland, 2004).These fungi account for the largest number of total described marine fungal compounds and produce highest number of novel metabolites (Bugni and Ireland, 2004).
Encouraged by the idea of "Drugs from the Sea", the chemists have identified many bioactive compounds with novel structures from marine bio-resources in recent years (Faulkner, 2000;Marris, 2006).Among them, marine derived fungi have contributed an important proportion.Many marine fungal strains were isolated, screened and reported to produce novel antimicrobial compounds like alkaloids, macrolides, terpenoids, peptide derivatives and other types (Bugni and Ireland, 2004;Saleem et al., 2007).These marine fungal derived compounds have provided us with new choices to fight infectious diseases.For example, the marine fungus Pestalotia spp.isolated from the surface of the brown alga Rosenvingea spp. was able to produce a new chlorinated benzophenone compound pestalone, which showed potent antibiotic activity against multi drug resistance Staphylococous aureus (MRSA), revealing its potential as a new antibiotic.Current studies indicate that complex interactions exist between the host and their epi/endophytic fungi, e.g. the host provides organic nutrition and epi/endophytes act as chemical guards (Tan and Zou, 2001;Bugni and Ireland, 2004).As compared to free-living marine fungi, the epi/endophytic marine fungi have drawn more interest of natural product chemists in search for novel antimicrobial or other active compounds.According to Bugni and Ireland (2004) among the new compounds reported from marine derived fungi till 2002, most of them are produced by epi/endophytes isolated from plants, invertebrates and woody substrates.

CONCLUSION
The world oceans comprise a rich diversity of microbial life with current estimates reaching over a million different species.The vast metabolic diversity of marine microorganisms is underpinned by novel enzymatic functions.While marine microorganisms have already proven to be a rich source of biologically active compounds (bioactives), recent large-scale surveys indicated the existence of thousands of other yet undescribed protein families.Chemically mediated interactions and communications between the microorganisms and their eukaryotic hosts are also likely to have a significant impact on the composition and function of surface consortia.These factors shape the composition and properties of the surface community.The ocean represents a rich resource of even more novel compounds with great potential as pharmaceutical, nutritional supplements, cosmetics, agrichemicals and enzymes, where each of these marine bioproducts have a strong potential market value.