Skip to main content

Advertisement

Log in

Novel aromatic polyketides from soil Streptomyces spp.: purification, characterization and bioactivity studies

  • Original Paper
  • Published:
World Journal of Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Aromatic polyketides are important therapeutic compounds which include front line antibiotics and anticancer drugs. Since most of the aromatic polyketides are known to be produced by soil dwelling Streptomyces, 54 Streptomyces strains were isolated from the soil samples. Five isolates, R1, B1, R3, R5 and Y8 were found to be potent aromatic polyketide producers and were identified by 16S rRNA gene sequencing as Streptomyces spectabilis, Streptomyces olivaceus, Streptomyces purpurascens, Streptomyces coeruleorubidus and Streptomyces lavendofoliae respectively. Their sequences have been deposited in the GenBank under the accession numbers KF468818, KF681280, KF395224, KF527511 and KF681281 respectively. The Streptomyces strains were cultivated in the media following critically optimised culture conditions. The resulting broth extracts were fractionated on a silica gel column and preparative TLC to obtain pure compounds. The pure compounds were tested for bioactivity and the most potent compound from each isolate was identified by UV–Vis, IR and NMR spectroscopic methods. Isolated S. spectabilis (R1), yielded one potent compound identified as dihydrodaunomycin with an MIC of 4 µg/ml against Bacillus cereus and an IC50 value of 24 µM against HeLa. S. olivaceus (B1), yielded a comparatively less potent compound, elloramycin. S. purpurascens (R3) yielded three compounds, rhodomycin, epelmycin and obelmycin. The most potent compound was rhodomycin with an MIC of 2 µg/ml against B. cereus and IC50 of 15 µM against HeLa. S. coeruleorubidus (R5), yielded daunomycin showing an IC50 of 10 µM and also exhibiting antimetastatic properties against HeLa. S. lavendofoliae (Y8), yielded a novel aclacinomycin analogue with IC50 value of 2.9 µM and potent antimetastatic properties at 1 µM concentration against HeLa. The study focuses on the characterization of aromatic polyketides from soil Streptomyces spp., which can serve as potential candidates for development of chemotherapeutic drugs in future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Anderson AS, Wellington EM (2001) The taxonomy of Streptomyces and related genera. Int J Syst Evol Microbiol 51(3):797–814

    Article  PubMed  CAS  Google Scholar 

  • Arcamone F, Cassinelli G, Fantini G, Grein A, Orezzi P, Pol C, Spalla C (1969) Adriamycin, 14-hydroxydaimomycin, a new antitumor antibiotic from S. Peucetius var. caesius. Biotechnol Bioeng 11(6):1101–1110

    Article  PubMed  CAS  Google Scholar 

  • Arcamone F, Cassinelli G, Franceschi G, Penco S, Pol C, Redaelli S, Selva A (1972) Structure and physicochemical properties of adriamycin (doxorubicin). In: International symposium on adriamycin, Springer, Berlin, pp. 9–22

    Chapter  Google Scholar 

  • Arifuzzaman M, Khatun MR, Rahman H (2010) Isolation and screening of actinomycetes from Sundarbans soil for antibacterial activity. Afr J Biotechnol 9:4615–4619

    Google Scholar 

  • Arthington-Skaggs BA, Lee-Yang W, Ciblak MA, Frade JP, Brandt ME, Hajjeh RA, Harrison LH, Sofair AN, Warnock DW, Candidemia Active Surveillance Group (2002) Comparison of visual and spectrophotometric methods of broth microdilution MIC end point determination and evaluation of a sterol quantitation method for in vitro susceptibility testing of fluconazole and itraconazole against trailing and nontrailing Candida isolates. Antimicrob Agents Chemother 46(8):2477–2481

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Augustine SK, Bhavsar SP, Kapadnis BP (2005) A non-polyene antifungal antibiotic from Streptomyces albidoflavus PU 23. J Biosci 30(2):201–211

    Article  PubMed  CAS  Google Scholar 

  • Batel PL, Connors NC, Strohl WR (1990) Biosynthesis of anthracyclines: analysis of mutants of Streptomyces sp. strain C5 blocked in daunomycin biosynthesis. J Gen Microbiol 136(9):1877–1886

    Article  Google Scholar 

  • Begde D, Bundale S, Mashitha P, Rudra J, Nashikkar N, Upadhyay A (2011) Immunomodulatory efficacy of nisin—a bacterial lantibiotic peptide. J Pept Sci 17(6):438–444

    Article  PubMed  CAS  Google Scholar 

  • Bervanakis G (2008) Detection and expression of biosynthetic genes in actinobacteria. Flinders University, School of Medicine, Department of Medical Biotechnology

  • Bouma J, Beijnen JH, Bult A, Underberg WJ (1986) Anthracycline antitumour agents. Pharm World Sci 8(2):109–133

    CAS  Google Scholar 

  • Bundale S, Begde D, Nashikkar N, Kadam T, Upadhyay A (2014) Isolation of aromatic polyketide producing soil streptomyces using combinatorial screening strategies. OALib. https://doi.org/10.4236/oalib.preprints.1200010

    Article  Google Scholar 

  • Bundale S, Begde D, Nashikkar N, Kadam T, Upadhyay A (2015) Optimization of culture conditions for production of bioactive metabolites by Streptomyces spp. isolated from soil. Adv Microbiol 5(06):441–451

    Article  CAS  Google Scholar 

  • Dickens ML, Priestley ND, Strohl WR (1997) In vivo and in vitro bioconversion of epsilon-rhodomycinone glycoside to doxorubicin: functions of DauP, DauK, and DoxA. J Bacteriol 179(8):2641–2650

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Donadio S, Maffioli S, Monciardini P, Sosio M, Jabes D (2010) Antibiotic discovery in the twenty-first century: current trends and future perspectives. J Antibiot 63(8):423–430

    Article  PubMed  CAS  Google Scholar 

  • Dornberger K, Hübener R, Ihn W, Thrum H, Radics L (1985) Microbial conversion of daunorubicin into N-acetyl-13 (S)-dihydrodaunomycin and bisanhydro-13-dihydrodaunomycinone. J Antibiot 38(9):1219–1225

    Article  PubMed  CAS  Google Scholar 

  • Drautz H, Reuschenbach P, Zähner H, Rohr J, Zeeck A (1985) Metabolic products of microorganisms. 225 Elloramycin, a new anthracycline-like antibiotic from Streptomyces olivaceus. J Antibiot 38(10):1291–1301

    Article  PubMed  CAS  Google Scholar 

  • Fujiwara A, Hoshino T, Westley JW (1985) Anthracycline antibiotics. Crit Rev Biotechnol 3(2):133–157

    Article  Google Scholar 

  • Gebäck T, Schulz MM, Koumoutsakos P, Detmar M (2009) TScratch: a novel and simple software tool for automated analysis of monolayer wound healing assays. Biotechniques 46(4):265–274

    Article  PubMed  CAS  Google Scholar 

  • Hertweck C, Luzhetskyy A, Rebets Y, Bechthold A (2007) Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. Nat Prod Rep 24(1):162–190

    Article  PubMed  CAS  Google Scholar 

  • Holkar SK, Begde DN, Nashikkar NA, Kadam TA, Upadhyay AA (2013a) Optimization of some culture conditions for improved biomass and antibiotic production by Streptomyces spectabilis isolated from soil. Int J Pharm Sci Res 4(8):2980

    Google Scholar 

  • Holkar SK, Begde DN, Nashikkar NA, Kadam TA, Upadhyay AA (2013b) Rhodomycin analogues from Streptomyces purpurascens: isolation, characterization and biological activities. SpringerPlus 2:93

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Johdo O, Watanabe Y, Ishikura T, Yoshimoto A, Naganawa H, Sawa T, Takeuchi T (1991) Anthracycline metabolites from Streptomyces violaceus A262. J Antibiot 44(10):1121–1129

    Article  PubMed  CAS  Google Scholar 

  • Kim WS, Youn DJ, Cho WT, Kim MK, Kim HR, Rhee SK, Choi ES (1995a) Improved production, and purification of aclacinomycin A from Streptomyces lavendofoliae DKRS. J Microbiol Biotechnol 5(5):297–301

    CAS  Google Scholar 

  • Kim WS, Youn DJ, Kim HR, Rhee SK, Choi ES (1995b) Metabolic conversion of aclacinomycins B and Y to A by pH shift during fermentation with Streptomyces lavendofoliae DKRS. Biotechnol Tech 9(9):671–676

    Article  CAS  Google Scholar 

  • Kim HS, Hong YS, Kim YH, Yoo OJ, Lee JJ (1996) New anthracycline metabolites produced by the aklavinone 11-hydroxylase gene in Streptomyces galilaeus ATCC 31133. J Antibiot 49(4):355–360

    Article  PubMed  CAS  Google Scholar 

  • Kitamura I, Tobe H, Yoshimoto A, Oki T, Naganawa H, Takeuchi T, Umezawa H (1981) Biosynthesis of aklavinone and aclacinomycins. J Antibiot 34(11):1498–1500

    Article  PubMed  CAS  Google Scholar 

  • Kizek R, Adam V, Hrabeta J, Eckschlager T, Smutny S, Burda JV, Frei E, Stiborova M (2012) Anthracyclines and ellipticines as DNA-damaging anticancer drugs: recent advances. Pharmacol Ther 133(1):26–39

    Article  PubMed  CAS  Google Scholar 

  • Kummar S, Gutierrez M, Doroshow JH, Murgo AJ (2006) Drug development in oncology: classical cytotoxics and molecularly targeted agents. Br J Clin Pharmacol 62(1):15–26

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Laatsch H, Fotso S (2008) Naturally occurring anthracyclines. In: Anthracycline chemistry biology. Springer, Berlin, pp. 3–74

    Chapter  Google Scholar 

  • Liang CC, Park AY, Guan JL (2007) In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc 2(2):329–333

    Article  PubMed  CAS  Google Scholar 

  • Liu Q, Liu C, Yu J, Yan J, Qi X (2012) Analysis of the ketosynthase genes in Streptomyces and its implications for preventing reinvestigation of polyketides with bioactivities. J Agric Sci 4(7):262–270

    CAS  Google Scholar 

  • Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65(1–2):55–63

    Article  PubMed  CAS  Google Scholar 

  • Oki T, Kitamura I, Yoshimoto A, Matsuzawa Y, Shibamoto N, Ogasawara T, Inui T, Takamatsu A, Takeuchi T, Masuda T, Hamada M (1979) Antitumor anthracycline antibiotics, aclacinomycin A and analogues. I. Taxonomy, production, isolation and physicochemical properties. J Antibiot 32(8):791–800

    Article  PubMed  CAS  Google Scholar 

  • Rahman AM, Yusuf SW, Ewer MS (2007) Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomed 2(4):567–583

    CAS  Google Scholar 

  • Roe MT, Vega E, Pillai SD (2003) Antimicrobial resistance markers for class 1 and class 2 integron-bearing Escherichia coli from irrigation water and sediments. Emerg Infect Dis 9(7):822–826

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Saito S, Katsuda Y, Johdo O, Yoshimoto A (1995) New rhodomycin analogs, SS-288A and SS-288B, produced by a Streptomyces violaceus A262 mutant. Biosci Biotechnol Biochem 59(1):135–137

    Article  PubMed  CAS  Google Scholar 

  • Shoji J, Kozuki S, Nishimura H, Mayama M, Motokawa K, Tanaka Y, Otsuka H (1968) Isolation of an antibiotic S-583-B, related to rhodomycin A and B. J Antibiot 11:643

    Article  Google Scholar 

  • Silverstein RM, Webster FX, Kiemle DJ, Bryce DL (2014) Spectrometric identification of organic compounds. Wiley, New York

    Google Scholar 

  • Staley AL, Rinehart KL (1994) Spectomycins, new antibacterial compounds produced by Streptomyces spectabilis: isolation, structures, and biosynthesis. J Antibiot 47(12):1425–1433

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Katsaros D, Shen Y, Fu Y, Canuto EM, Benedetto C, Lu L, Chu WM, Risch HA, Yu H (2015) Biological and clinical significance of MAD2L1 and BUB1 genes frequently appearing in expression signatures for breast cancer prognosis. PLoS ONE 10(8):e0136246

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Workman JJ (2000) Handbook of organic compounds: NIR, IR, Raman and UV-vis spectra featuring polymers and surfactants, vol 3. Academic Press, London

    Google Scholar 

  • Yoshimoto A, Oki T, Takeuchi T, Umezawa H (1980) Microbial conversion of anthracyclinones to daunomycin by blocked mutants of Streptomyces coeruleorubidus. J Antibiot 33(10):1158–1166

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank the NMR Research Centre, IISc, Bangalore and Material Science Department of VNIT, Nagpur, India for providing assistance in NMR and FT-IR analysis respectively.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sunita Bundale.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bundale, S., Begde, D., Pillai, D. et al. Novel aromatic polyketides from soil Streptomyces spp.: purification, characterization and bioactivity studies. World J Microbiol Biotechnol 34, 67 (2018). https://doi.org/10.1007/s11274-018-2448-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11274-018-2448-1

Keywords

Navigation