Abstract
As part of the endeavor for search of effective bioactive compounds, an untapped Arabian Sea environment is selected as a sampling source for the isolation of chemically-talented actinomycete strains. We have isolated an actinomycete strain from the sea sediments belonging to the genus Streptomyces (Accession No. KJ020688) with having potent cytotoxicity (84 %) against brine shrimps nauplii. Isolated strain also showed substantial antibacterial activity against Bacilus subtilis, Escherichia coli and Acinetobacter test strains. Fractions with significant antitumor activity obtained from the extract of 20 l fermentation broth were structurally elucidated and revealed with the production of compounds named as iturin A6 and actinomycin-D. The cyclic lipopeptide iturin A6 display outstanding novel antitumor activities against three tumor cell lines viz. HeLa, MCF-7, Hep G2 with IC50 values of 1.73 ± 0.9, 6.44 ± 0.6 and 8.9 ± 1.09 μg/ml respectively. This peptide is found to be ineffective against RD tumor cells. The second polypeptide actinomycin-D is found to be active against the entire panel of tumor cell lines used. It exhibited stronger activities with IC50-values of <0.9 μg/ml against HeLa and MCF-7, while 11.72 ± 0.9 and 1.19 ± 0.8 against Hep G2 and RD cells respectively. Results from the culture optimization experiments of this strain showed greater yield of secondary metabolites while culturing in glucose–yeast extract–malt extract (M2) medium under culture conditions set as follows, shaking at 95 rpm, pH 7.8, incubation temperature 28 °C, for 168 h. As such this is the first report for the isolation of any iturin family member from actinomycetes group with having antitumor activity.
Similar content being viewed by others
References
Adinarayana K, Ellaiah P, Srinivasulu B, Devi RB, Adinarayana G (2003) Response surface methodological approach to optimize the nutritional parameters for neomycin production by Streptomyces marinensis under solid-state fermentation. Process Biochem 38:1565–1572
Baltz RH, Miao V, Wrigley SK (2005) Natural products to drugs: daptomycin and related lipopeptide antibiotics. Nat Prod Rep 22:717–741
Becker B, Lechevalier M, Lechevalier H (1965) Chemical composition of cell-wall preparations from strains of various form-genera of aerobic actinomycetes. Appl Microbiol 13:236–243
Bonmatin J-M, Laprévote O, Peypoux F (2003) Diversity among microbial cyclic lipopeptides: iturins and surfactins. Activity–structure relationships to design new bioactive agents. Com Chem High Throughput Screen 6:541–556
Bull AT, Stach JE (2007) Marine actinobacteria: new opportunities for natural product search and discovery. Trends Microbiol 15:491–499
Chen H, Wang L, Su C, Gong G, Wang P, Yu Z (2008) Isolation and characterization of lipopeptide antibiotics produced by Bacillus subtilis. Lett Appl Microbiol 47:180–186
Cragg GM, Newman DJ (2005) Plants as a source of anti-cancer agents. J Ethnopharmacol 100:72–79
Dagher R, Helman L (1999) Rhabdomyosarcoma: an overview. Oncologist 4:34–44
Etchegaray A et al (2008) Effect of a highly concentrated lipopeptide extract of Bacillus subtilis on fungal and bacterial cells. Arch Microbiol 190:611–622
Feliu L, Planas M (2005) Cyclic peptides containing biaryl and biaryl ether linkages. Int J Pept Res Ther 11:53–97
Fenical W, Jensen PR (2006) Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol 2:666–673
Fiedler H-P et al (2005) Marine actinomycetes as a source of novel secondary metabolites. Antonie Van Leeuwenhoek 87:37–42
Jensen PR, Mincer TJ, Williams PG, Fenical W (2005) Marine actinomycete diversity and natural product discovery. Antonie Van Leeuwenhoek 87:43–48
Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150
Kim S-y et al (2007) Surfactin from Bacillus subtilis displays anti-proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression. FEBS Lett 581:865–871
Küster E, Williams S (1964) Selection of media for isolation of streptomycetes. Nature 202:928–929
Lackner H, Bahner I, Shigematsu N, Pannell LK, Mauger AB (2000) Structures of five components of the actinomycin Z complex from Streptomyces fradiae, two of which contain 4-chlorothreonine. J Nat Prod 63:352–356
Lam KS (2006) Discovery of novel metabolites from marine actinomycetes. Curr Opin Microbiol 9:245–251
Lane AL, Moore BS (2011) A sea of biosynthesis: marine natural products meet the molecular age. Nat Prod Rep 28:411–428
Liu X, Tao X, Zou A, Yang S, Zhang L, Mu B (2010) Effect of themicrobial lipopeptide on tumor cell lines: apoptosis induced by disturbing the fatty acid composition of cell membrane. Prot Cell 1:584–594
Ma Z, Wang N, Hu J, Wang S (2012) Isolation and characterization of a new iturinic lipopeptide, mojavensin a produced by a marine-derived bacterium Bacillus mojavensis B0621A. J Antibiot 65:317–322
Macedo JA, Sette LD, Sato HH (2007) Optimization of medium composition for transglutaminase production by a Brazilian soil Streptomyces sp electron. J Biotechnol 10:618–626
Mao X et al (2007) Optimizing the medium compositions for accumulation of the novel FR-008/candicidin derivatives CS101 by a mutant of Streptomyces sp. using statistical experimental methods. Process Biochem 42:878–883
Mclaughlin JL (1991) Crown gall tumours on potato discs and brine shrimp lethality: two simple bioassays for higher plant screening and fractionation. Methods Plant Biochem 6:1–32
Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55–63
Naine SJ, Devi CS, Mohanasrinivasan V (2014) Antimicrobial, antioxidant and cytotoxic activity of marine Streptomyces parvulus VITJS11 crude extract. Braz Arch Biol Technol 58:198–207
Ongena M, Jacques P (2008) Bacillus lipopeptides: versatile weapons for plant disease biocontrol. Trends Microbiol 16:115–125
Ravikumar S, Gnanadesigan M, Thajuddin N, Chakkaravarthi V, Banerjee MB (2010) Anticancer property of sponge associated actinomycetes along Palk Strait. J Pharm Res 3(10):2415–2417
Sajid I, Yao CBFF, Shaaban KA, Hasnain S, Laatsch H (2009) Antifungal and antibacterial activities of indigenous Streptomyces isolates from saline farmlands: prescreening, ribotyping and metabolic diversity. World J Microbiol Biotechnol 25:601–610
Sharma D, Mandal SM, Manhas RK (2014) Purification and characterization of a novel lipopeptide from Streptomyces amritsarensis sp. nov. active against methicillin-resistant Staphylococcus aureus. AMB Express 4(1):50
Et Shirling, Gottlieb D (1966) Method for characterization of Streptomyces species. Int J Syst Evolut Microbiol 16(3):313–340
Sivapathasekaran C, Das P, Mukherjee S, Saravanakumar J, Mandal M, Sen R (2010) Marine bacterium derived lipopeptides: characterization and cytotoxic activity against cancer cell lines. Int J Pept Res Ther 16:215–222
Solis PN, Wright CW, Anderson MM, Gupta MP, Phillipson JD (1993) A microwell cytotoxicity assay using Artemia salina (brine shrimp). Planta Med 59:250–252
Taddei A, Rodríguez MJ, Márquez-Vilchez E, Castelli C (2006) Isolation and identification of Streptomyces spp. from Venezuelan soils: morphological and biochemical studies I. Microbiol Res 161:222–231
Thasana N, Prapagdee B, Rangkadilok N, Sallabhan R, Aye SL, Ruchirawat S, Loprasert S (2010) Bacillus subtilis SSE4 produces subtulene A, a new lipopeptide antibiotic possessing an unusual C15 unsaturated β-amino acid. FEBS Lett 584:3209–3214
Volpon L et al (2007) NMR structure determination of a synthetic analogue of bacillomycin Lc reveals the strategic role of l-Asn1 in the natural iturinic antibiotics. Spectrochim Acta Part A 67:1374–1381
Xie J-J et al (2011) FW523-3, a novel lipopeptide compound, induces apoptosis in cancer cells. Mol Med Rep 4:759–763
Zhang HL, Hua HM, Pei YH, Yao XS (2004) Three new cytotoxic cyclic acylpeptides from marine Bacillus sp. Chem Pharm Bull 52:1029–1030
Acknowledgments
The authors are thankful to Higher Education Commission (HEC) Pakistan for providing financial support under IRSIP Scholarship Program for the completion of this research work. We are also thankful to Dr. David L. Zechel and Mr. XiMing Zhu for their help in Mass spectrometric analysis and Dr. Françoise Sauriol for her help regarding NMR experiments.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Usman Aftab and Imran Sajid confirm that for this article content they have no conflict of interest.
Human and Animal Rights
This article does not contain studies with human or animal subjects that should be approved by Ethical Committee.
Informed Consent
The article does not contain any studies related to patients.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Aftab, U., Sajid, I. Antitumor Peptides from Streptomyces sp. SSA 13, Isolated from Arabian Sea. Int J Pept Res Ther 23, 199–211 (2017). https://doi.org/10.1007/s10989-016-9552-6
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10989-016-9552-6