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Journal of
eISSN: 2373-437X

Microbiology & Experimentation

Review Article Volume 6 Issue 6

Marine peptides act as novel chemotherapeutic agent

Akanksha Srivastava,1 Vaibhav Mishra2

1Division of Microbiology, CSIR-Central Drug Research Institute, India
2Department of Environmental Microbiology, Babasaheb Bhimrao Ambedkar University, India

Correspondence: Dr. Vaibhav Mishra, Assistant Professor, Industrial Microbiology (Innovative Course), Department of Environmental Microbiology, Babasaheb Bhimrao Ambedkar University, Lucknow-226025, U.P. India, Tel 91-9450332710

Received: March 01, 2017 | Published: December 27, 2018

Citation: Srivastava A, Mishra V. Marine peptides act as novel chemotherapeutic agent. J Microbiol Exp. 2018;6(6):267-270. DOI: 10.15406/jmen.2018.06.00227

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Abstract

The marine environment represents a largely unexplored source of new microbes (bacteria, fungi, microalgae-cyanobacteria) that are potent producers of bioactive peptides. Here, we have discussed some novel peptides isolated from marine species exhibiting antibacterial, antifungal, antiviral, antiprotozoal activities. Therefore, marine peptides have attracted a great deal of attention due to their potential effects in promoting health and reducing disease. We have also discussed the extraction and commercial exploitation of peptides to become a possible future drug. Advancements in isolated techniques have allowed us easy access of less explored environment. Here, we summarize the future aim and scope of commercial application and production of microbial peptides from marine sources.

Keywords: microalgae, cyanobacteria antiviral, antiprotozoal, antitumour,

Introduction

Emergence of drug-resistant pathogens and infectious diseases caused by bacteria, fungi and viruses increases the demand of developing novel and effective antibiotics. For the discovery of new antibiotics terrestrial environment was centralized for more than 50 years, and marine sources have remained unexplored for production of new anti-infectious metabolites. Now-these-days research has been focused on ocean as it occupies almost 70% of earth’s surface and it provides a unique source of chemical compounds with potential bioactivities.1 In the last few decades, marine sources have played a major role for exploring and developing new drugs.2 But still many bioactive metabolites have to be explored, because of the difficulties in cultivation of deep water habitats. The marine habitat represents a new source of microbes including bacteria, fungi, microalgae-cyanobacteria) that can be effective producers of bioactive metabolites.3

Many marine species (like; bacteria, fungus, algae, fish and crab) secrets peptides so extensive research has been conducted on them. Bioactive marine peptides are effective due to their structural properties like amino acid composition and sequences with varying degrees of action. Marine peptides are currently used as antibiotics against infectious diseases such as human immunodeficiency virus (HIV) and conditions of multiple bacterial infections, antitumour, anticancer, antimicrotubule, antiproliferative and in cytotoxic activities.4‒7 Therefore, marine peptides have attracted a great deal of attention due to their potential effects in promoting health and reducing disease. In this mini-review, we discuss the marine peptides isolation and extraction from varying sources, also their activity against bacterial, fungal, protozoan and viral infections with current status of peptides at commercial level.

Marine microorganisms are major sources of microbial peptides

Marine microbial species survive in a stressful habitat, under cold, lightless, and high-pressure conditions. These factors involved in development of unique metabolisms, and result in the production of novel metabolites that differ from terrestrial organisms. Thus, marine microbes offer a magnificent source for the discovery of new compounds with different activities, including antimicrobial, anti-protozoan, anti-tuberculosis, and antiviral properties.8,9

Peptides from marine bacteria: A large volume of unknown marine microbes are present in environment and to be a very good source of novel molecules crack many unsolved queries. Bacteria are the best source for production of microbial peptides. They are able to produce many bioactive molecules in the marine, principally to keep away their predators and protecting themselves. Furthermore, marine bacteria produces novel microbial peptides that showing antitumour, anticoagulant and cardio protective properties.10 According to literatures some of the unique properties of bacterial peptides, like their ability to grow and functionally active at extremely elevated salt concentrations, make them good potential targets for development of new and novel molecules against various diseases.

Peptides from marine fungi: All forms of life are present in the oceanic environment especially, fungi play a key role to isolate and produce marine peptides. There are two types of marine fungi obligate and facultative.11 Obligate fungi are grown completely in a marine or estuarine habitat whereas facultative fungi are grown and sporulate in terrestrial or freshwater.12 Marine fungi have proven to be a rich and promising source of novel therapeutics agents. Near about 272 microbial peptides have been isolated from marine fungi and the number is still increasing.13 In addition, most of these microbial peptides are analogues of those discovered previously from terrestrial fungi.14

Peptides from marine sponges: Marine sponges (phylum Porifera) are one of the richest sources of pharmacologically-active chemicals. They are sessile marine feeders that have developed efficient defense mechanisms against foreign attackers such as viruses, bacteria, or eukaryotic organisms. It has been suggested that many of the bioactive metabolites isolated from sponges and their associated microorganisms are produced by functional enzyme clusters.15,16 The huge number of different secondary metabolites discovered in marine sponges and the complexity of the compounds and their biosynthetic pathways can be regarded as their importance for survival. As infectious microbes evolve and develop resistance to existing pharmaceuticals, marine sponges provide novel leads against bacterial, fungal and viral diseases.

Peptides from marine algae: Algae are very simple chlorophyll-containing organisms composed of one cell or grouped together in colonies or as organisms with many cells, sometimes collaborating together as simple tissues.17 Algae are heterogeneous group of plants with a long fossil history. Blue-green algae (cyanobacteria) contain chlorophyll a and related compounds. These algae are ancient photosynthetic prokaryotic organisms that producing biologically active metabolites with diverse chemical structures such as nitrogenous compounds and cyclic polyethers.18 Recently, several marine cyanobacterial have been the focused due to their effective biological activities and unique structures.

Peptides from marine invertebrate: Apart from microbes some invertebrates are also produces peptides and these peptides have some unique properties especially peptides from fishes are using as novel chemotherapeutics agents against microbes. Fish peptides are showing broad-spectrum antimicrobial activity against both fish and human pathogens. These peptides encoding genes are highly responsive to microbes and innate immunostimulatory molecules. Recent research has reported some unique properties of fish peptides, including their ability to act even at very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials.5 Some marine peptides from these different sources with their antagonist activity are discussed in Table 1.

Source

Name of
Peptide

Activity

Pharmacologic
Activity

Bacterium: Brevibacillus
laterosporus

Tauramamide (3)

Antibacterial

Enterococcussp. inhibition

Bacterium:
Streptomycessp.

Anthracimycin
(35)

Antibacterial

B. anthracis, Enterococcus facecalis, Streptococcus pneumonia, S. aureus, MSSA, MRSA, vanco-mycin-resistant S. aureus inhibition

Bacterium:
Rapidithrix sp.

Ariakemicins A (25), B (26)

Antibacterial

Brevibacteriumsp.,
S. aureus, B. subtilis

Bacterium:
Bacillus silvestris

Bacillistatins 1
(7), 2 (8)

Antibacterial

Streptococcus.
pneumoniainhibition

Bacterium:
Nocardiopsis sp

Nacardiopsis
thiopeptide
TP-1161 (9)

Antibacterial

Vancomycin-resistant
Enterococcus faecium
inhibition

Bacterium:
Phaeobacter sp

Indigoidine (15)

Antibacterial

Vibrio fischeriinhibition

Bacterium:
Photobacteriumsp.

Unnarmicins A
(16), C (17)

Antibacterial

Pseudovibriosp.
inhibition

Bacterium:
Photobacteriumsp.

Ngercheumi-cins A–D (18–21)

Antibacterial

Gram negative strain
inhibition

Bacterium:
Photobacteriumsp.

Solonamidine A (22), B (23)

Antibacterial

S. aureus, Methicillin-resistant S. aureus (MRSA)

Bacterium:
Pseudomonassp.

Cyclo-peptides
(24)

Antibacterial

S. aureus, M. luteus, B. subtilis, E. coli, V. anguillarum

Fungus: Leucostoma persoonii

Cytosporones B (33), E (34)

Antibacterial

S. aureusUSA100,
MRSA, MSSA inhibition

Fish: Oreochromis
mossambicus

Hepcidin (4)

Antibacterial

Listeria monocytogenes,
S. aureus, and Enterococcus faecium inhibition

Jellyfish: Aurelia aurita

Aurelin (1)

Antibacterial

Escheichia coli inhibition

Bacterium:
Chondromyces
Pediculatus

Pedein A (39)

Antifungal

Rhizopus glutinis,
Saccharomyces cerevisae,
C. albicansinhibition

Sponge: Latrunculia sp.

Callipeltine J(37), K (38)

Antifungal

C. albicans

Sponge: Theonella sp.

TheuellamideF
(40), G (41)

Antifungal

C. albicansinhibition

Bacterium: Lyngbya majuscula

Dragomabin (54)

Antimalarial

Plasmodium falciparumW2
strain inhibition

Bacterium:
Oscillatoriasp.

Venturamid A (55), B (56)

Antimalarial

Plasmodium falciparumW2

Bacteriun: Microcystis aeruginosa

Aerucyamide A–D (57–60)

Antimalarial

Plasmodium falciparumK1

Bacterium:
Schizothrixsp.

Gallinamide A (61

Antimalarial

Plasmodium falciparumW2

Bacterium: Lyngbya majuscula

Lagunamide A (62), B (63)

Antimalarial

Plasmodium falciparum
NF54 strain inhibition

Bacterium:
Oscillatoria
nigro-viridis

Viridamide A (65), B (66)

Antiprotozoal

Leishmania mexicana,
Trypanosoma cruziinhibition

Bacterium:
Lyngbya majuscula

Almiramides B
(67), C (68)

Antiprotozoal

Leishmania donovani
inhibition

Bacterium:
Streptomycessp.

Valinomycin (69)

Antiprotozoal

Leishmania major&
Trypanosoma brucei inhibition

Fungus: A. fumigatus, Nectria inventa

Diketopiperazines (70–81)

Antiprotozoal

Trypanosoma brucei

Fungus:
Trichodermasp.

Trichoderin A (82), A1 (83), B (84)

Antitubercu-losis

Mycobacterium tuberculosis

Fungus: Aspergillus terreus

Asperterrestide A (98)

Antiviral

Anti-HIN1, Anti-H3N2

Sponge:
Siliquariaspongiamirabilis

Celebesides A (94), C (95)

Antiviral

 

Anti-HIV-1

Sponge:
Theonella swinhoei

Theopapu-amide A
(96), D (97)

Antiviral

 

Anti-HIV-1

Sponge:
Siliquariaspongia
mirabilis

Mirabamides A (85), C (86), D (87), E–H (88–91)

Antiviral

 

Anti-HIV-1

Sponge:
Homophymia sp.

Homophymine A–E (99–103),
A1–E1 (104–108)

Antiviral

 

Anti-HIV-1

Sponge: Theonella sp.

Koshikmaide B (109), F–H
(110–112)

Antiviral

 

Anti-HIV-1

Table 1 Marine peptides from diverse sources with anti-infective activities19

Isolation of marine peptides from microbes

To isolate the peptides from sea water sample at different depth is collected from ocean. A variety of pre-treatment methods including enrichment, physical, and chemical techniques (e.g., dry heat, exposure to 1%–1.5% phenol, sucrose-gradient centrifugation, and filtration through cellulose membrane filters) are employed to favor the isolation of specific genera and improve the recovery of marine peptides.20 These pre-treatment’s eliminate or strongly reduce the risk of contamination, thereby facilitating the isolation of marine peptides.

Extraction of marine peptides for commercial applications

Bioactive peptides or protein hydrolysates from marine species can be extracted and isolated by various methods in industrial-scale production. The organic solvent extraction method was used traditionally, but due to its time-consumption and costlier, some improved extraction techniques like pressurized solvent, supercritical fluid, pulsed electric field-assisted, microwave-assisted, ultrasound-assisted and enzyme-assisted are preferred.21

After the extraction procedure, the proteins are hydrolyzed into bioactive peptides. Enzymatic hydrolysis is preferred in the nutraceutical and pharmaceutical industries in order to avoid harsh chemical and physical treatment and preserve the functionality and nutritive values.22 A novel ultra filtration membrane bioreactor technology has recently emerged. Nowadays, marine peptide are obtained by multistep recycling membrane reactor combined with an ultra filtration membrane system to fractionate marine hydrolysates according to different molecular weight ranges.23 Some of marine peptides obtained from these sources are in clinical trials which have been elaborated in Table 2.

Source

Compound

Applications

Status

ω-conotoxin toxin from Conus magus

Ziconotide

 Analgesics

FDA approved

Dolabella auricularia

Brentuximab vedotin

Cancer treatment

FDA approved

Dolabella auricularia

Glembatumumab
vedotin

Cancer treatment

Phase I/II clinical study

pentapeptide from hydrolysate of dried bonito

Katsuobushi

Antihypertensive

Sold as
nutraceuticals

oligopeptide extract from Chlorella vulgaris

Dermochlorella®

Skin toner and
firmer

Sold as skin care
product

Aplidium albicans

Plitidepsin

Cancer treatment

Phase I/II
clinical study

Hemiasterella minor

HTI-286

Cancer treatment

Preclinical study

Elysia rufescens

Kahalalide F

Cancer treatment

Phase I clinical study

Elysia rufescens

Elisidepsin

Cancer treatment

Phase I clinical study

Hydrolysate of fish collagen and gelatin

Fish gelatin

Supplements and
bone health

Sold as nutraceuticals

Hydrolysate of fish protein

Stabilium
Protizen/Procalm

Anxiolytic

Sold as nutraceuticals

Hydrolysate of fish protein

Seacure

Intestinal health

Sold as nutraceuticals

Hydrolysate of fish protein

Nutripeptin®/
Hydro MN Peptide®

Postprandial blood
glucose control

Sold as nutraceuticals

Table 2 Marine peptides in clinical trials24

Conclusion

The discovery of bio regulatory roles with elucidation of the marine peptides mechanisms would promote the peptides to be used as potential drugs for treatment of diseases. With the advancement of marine peptides to the current preclinical and clinical stages, their contribution in the future shows some potential. New technologies and close collaborations between institutional and industrial investigators will be crucial to ensure the future success of marine peptides as novel therapeutics that can make a vital contribution to the treatment or prevention of various diseases.

Acknowledgements

The authors would like to thank the Council of Scientific and Industrial Research (CSIR), India and Babasaheb Bhimrao Ambedkar University to provide all the necessary facility for research.

Conflict of interest

No conflict of interest declared.

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