Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Isolation of two new stereochemical variants of streptophenazine by cocultivation of Streptomyces NIIST-D31, Streptomyces NIIST-D47, and Streptomyces NIIST-D63 strains in 3C2 combinations

The Journal of Antibiotics volume 76, pages 567–578 (2023)Cite this article

Subjects

Abstract

Cocultivation of combinations of Streptomyces species isolated from the same soil was explored to isolate novel secondary metabolites. Recently, we reported the isolation of a novel vicinal diepoxide of alloaureothin along with three carboxamides, 4-aminobenzoic acid, and 1,6-dimethoxyphenazine from the individual culture of Streptomyces luteireticuli NIIST-D31. Herein, cocultivation of NIIST-D31 with Streptomyces luteoverticillatus NIIST-D47 afforded two new stereochemical variants of streptophenazine (S1 and S2), and 1-N-methylalbonoursin, where the individual culture of NIIST-D47 primarily produced carbazomycins A, D, and E. The new streptophenazines and 1-N-methylalbonoursin were also observed during cocultivation of NIIST-D31 with Streptomyces thioluteus NIIST-D63, where the individual culture of NIIST-D63 strain afforded for the first time 2,2′-bipyridines (caerulomycinamide and dipyrimicin B), picolinamide, 2,3-dimethoxybenzamide, 2-hydroxy-3-methoxybenzamide, and 6-amino-2-pyridone along with known natural products aureothin and 1,6-dimethoxyphenazine. Finally, cocultivation of NIIST-D47 and NIIST-D63 strains produced carbazomycins B and C, alloaureothin, cyclo-(Leu-Pro), investiamide, and 4-aminobenzoic acid. Some of the compounds observed in the individual cultures were also produced in cocultivations. Improvement in the yield of secondary metabolites during cocultivation compared to individual culturing is well-known, which is noted here for vicinal diepoxide of alloaureothin. The production of new streptophenazines by cocultivation combinations with NIIST-D31 suggests that NIIST-D47 and NIIST-D63 may function as inducers in activating cryptic secondary metabolite-biosynthetic gene clusters. Cytotoxicity of the new streptophenazines in cancerous (MCF7 and MDA-MB-231) or non-cancerous (WI-38) cells were tested, however, they exhibited no significant activity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Baltz RH. Genome mining for drug discovery: progress at the front end. J Ind Microbiol Biotechnol. 2021;48. https://doi.org/10.1093/jimb/kuab044.

  2. Panter F, Bader CD, Müller R. Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics. Chem Sci. 2021;12:5994–6010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Aigle B, Lautru S, Spiteller D, Dickschat JS, Challis GL, Leblond P, et al. Genome mining of Streptomyces ambofaciens. J Ind Microbiol Biotechnol. 2014;41:251–63.

    Article  CAS  PubMed  Google Scholar 

  4. Ohnishi Y, Ishikawa J, Hara H, Suzuki H, Ikenoya M, Ikeda H, et al. Genome sequence of the streptomycin-producing microorganism Streptomyces griseus IFO 13350. J Bacteriol. 2008;190:4050–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee N, Hwang S, Lee Y, Cho S, Palsson B, Cho B-K. Synthetic biology tools for novel secondary metabolite discovery in streptomyces. J Microbiol Biotechnol. 2019;29:667–86.

    Article  CAS  PubMed  Google Scholar 

  6. Onaka H. Novel antibiotic screening methods to awaken silent or cryptic secondary metabolic pathways in actinomycetes. J Antibiot. 2017;70:865–70.

    Article  CAS  Google Scholar 

  7. Kim JH, Lee N, Hwang S, Kim W, Lee Y, Cho S et al. Discovery of novel secondary metabolites encoded in actinomycete genomes through coculture. J Ind Microbiol Biotechnol. 2021;48. https://doi.org/10.1093/jimb/kuaa001.

  8. Bekiesch P, Basitta P, Apel AK. Challenges in the heterologous production of antibiotics in Streptomyces. Arch Pharm. 2016;349:594–601.

    Article  CAS  Google Scholar 

  9. Yu M, Li Y, Banakar SP, Liu L, Shao C, Li Z et al. New metabolites from the co-culture of marine-derived actinomycete Streptomyces rochei MB037 and Fungus Rhinocladiella similis 35. Front Microbiol. 2019;10. https://doi.org/10.3389/fmicb.2019.00915.

  10. Abdelmohsen UR, Grkovic T, Balasubramanian S, Kamel MS, Quinn RJ, Hentschel U. Elicitation of secondary metabolism in actinomycetes. Biotechnol Adv. 2015;33:798–811.

    Article  CAS  PubMed  Google Scholar 

  11. Reen F, Romano S, Dobson A, O’Gara F. The sound of silence: activating silent biosynthetic gene clusters in marine microorganisms. Mar Drugs. 2015;13:4754–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Arora D, Gupta P, Jaglan S, Roullier C, Grovel O, Bertrand S. Expanding the chemical diversity through microorganisms co-culture: current status and outlook. Biotechnol Adv. 2020;40:107521.

    Article  PubMed  Google Scholar 

  13. Drissya T, Induja DK, Poornima MS, Jesmina ARS, Prabha B, Saumini M et al. A novel aureothin diepoxide derivative from Streptomyces sp. NIIST-D31 strain. J Antibiot. 2022. https://doi.org/10.1038/s41429-022-00547-1.

  14. Sakano K-I, Nakamura S. New antibiotics, carbazomycins A and B. II. Structural elucidation. J Antibiot. 1980;33:961–6.

    Article  CAS  Google Scholar 

  15. Naid T, Kitahara T, Kaneda M, Nakamura S. Carbazomycins C, D, E and F, minor components of the carbazomycin complex. J Antibiot. 1987;40:157–64.

    Article  CAS  Google Scholar 

  16. Kondo S, Katayama M, Marumo S. Carbazomycinal and 6-methoxycarbazomycinal as aerial mycelium formation-inhibitory substances of Streptoverticillium species. J Antibiot. 1986;39:727–30.

    Article  CAS  Google Scholar 

  17. Feng Z, Chen G, Zhang J, Zhu H, Yu X, Yin Y, et al. Characterization and complete genome analysis of the carbazomycin B-producing strain Streptomyces luteoverticillatus SZJ61. Curr Microbiol. 2019;76:982–7.

    Article  CAS  PubMed  Google Scholar 

  18. Yamasaki K, Kaneda M, Watanabe K, Ueki Y, Ishimaru K, Nakamura S, et al. New antibiotics, carbazomycins A and B. III. Taxonomy and biosynthesis. J Antibiot. 1983;36:552–8.

    Article  CAS  Google Scholar 

  19. Kaneda M, Naid T, Kitahara T, Nakamura S, Hirata T, Suga T, Carbazomycins G. and H, novel carbazomycin congeners containing a quinol moiety. J Antibiot. 1988;41:602–8.

    Article  CAS  Google Scholar 

  20. Shaaban KA, Shepherd MD, Ahmed TA, Nybo SE, Leggas M, Rohr J. Pyramidamycins A-D and 3-hydroxyquinoline-2-carboxamide; cytotoxic benzamides from Streptomyces sp. DGC1. J Antibiot. 2012;65:615–22.

    Article  CAS  Google Scholar 

  21. Shin C, Yonezawa Y, Ohno H. Synthesis of (3 Z,6 E)-1- N -Methylalbonoursin, a New Metabolite from Streptomyces albus. Agric Biol Chem. 1987;51:2033–4.

    CAS  Google Scholar 

  22. Bauman KD, Li J, Murata K, Mantovani SM, Dahesh S, Nizet V, et al. Refactoring the cryptic streptophenazine biosynthetic gene cluster unites phenazine, polyketide, and nonribosomal peptide biochemistry. Cell Chem Biol. 2019;26:724–736.e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yang Z, Jin X, Guaciaro M, Molino BF, Mocek U, Reategui R, et al. The revised structure, total synthesis, and absolute configuration of Streptophenazine A. Org Lett. 2011;13:5436–9.

    Article  CAS  PubMed  Google Scholar 

  24. Kunz A, Labes A, Wiese J, Bruhn T, Bringmann G, Imhoff J. Nature’s lab for derivatization: new and revised structures of a variety of streptophenazines produced by a sponge-derived streptomyces strain. Mar Drugs. 2014;12:1699–714.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Liang Y, Chen L, Ye X, Anjum K, Lian X-Y, Zhang Z. New streptophenazines from marine Streptomyces sp. 182SMLY. Nat Prod Res. 2017;31:411–7.

    Article  CAS  PubMed  Google Scholar 

  26. Bunbamrung N, Dramae A, Srichomthong K, Supothina S, Pittayakhajonwut P, Streptophenazines I–L. from Streptomyces sp. BCC21835. Phytochem Lett. 2014;10:91–94.

    Article  CAS  Google Scholar 

  27. Divekar PV, Read G, Vining LC. Caerulomycin, a new antibiotic from Streptomyces caeruleus Baldacci. II. Structure. Can J Chem. 1967;45:1215–23.

    Article  CAS  Google Scholar 

  28. Fu P, Wang S, Hong K, Li X, Liu P, Wang Y, et al. Cytotoxic bipyridines from the marine-derived actinomycete Actinoalloteichus cyanogriseus WH1-2216-6. J Nat Prod. 2011;74:1751–6.

    Article  CAS  PubMed  Google Scholar 

  29. Izuta S, Kosaka S, Kawai M, Miyano R, Matsuo H, Matsumoto A, et al. Dipyrimicin A and B, microbial compounds isolated from Amycolatopsis sp. K16-0194. J Antibiot. 2018;71:535–7.

    Article  CAS  Google Scholar 

  30. Ali MA, Punniyamurthy T. Palladium-catalyzed one-pot conversion of aldehydes to amides. Adv Synth Catal. 2010;352:288–92.

    Article  CAS  Google Scholar 

  31. Gerber NN. Phenazines, phenoxazinones, and dioxopiperazines from Streptomyces thioluteus. J Org Chem. 1967;32:4055–7.

    Article  CAS  PubMed  Google Scholar 

  32. Hirata Y, Nakata H, Yamada K, Okuhara K, Naito T. The structure of aureothin, a nitro compound obtained from Streptomyces thioluteus. Tetrahedron. 1961;14:252–74.

    Article  CAS  Google Scholar 

  33. Henrot M, Jean A, Peixoto PA, Maddaluno J, de Paolis M. Flexible total synthesis of (±)-aureothin, a potent antiproliferative agent. J Org Chem. 2016;81:5190–201.

    Article  CAS  PubMed  Google Scholar 

  34. Ueda J, Hashimoto J, Nagai A, Nakashima T, Komaki H, Anzai K, et al. New aureothin derivative, alloaureothin, from Streptomyces sp. MM23. J Antibiot. 2007;60:321–4.

    Article  CAS  Google Scholar 

  35. Kumar N, Mohandas C, Nambisan B, Kumar DRS, Lankalapalli RS. Isolation of proline-based cyclic dipeptides from Bacillus sp. N strain associated with rhabitid entomopathogenic nematode and its antimicrobial properties. World J Microbiol Biotechnol. 2013;29:355–64.

    Article  CAS  PubMed  Google Scholar 

  36. Chang C-W, Chang H-S, Cheng M-J, Liu T-W, Hsieh S-Y, Yuan G-F, et al. Inhibitory effects of constituents of an endophytic fungus Hypoxylon investiens on nitric oxide and interleukin-6 production in RAW264.7 macrophages. Chem Biodivers. 2014;11:949–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Financial support from DST, Science and Engineering Research Board, India (grant number: CRG/2020/004993) is gratefully acknowledged. D.K.I. and A.R.S.J. are grateful to UGC for senior research fellowship.

Author information

Authors and Affiliations

  1. Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, 695019, Kerala, India

    D. K. Induja, Manu M. Joseph, Shanmughan Shamjith, Nagaraja Ingaladal, Kaustabh Kumar Maiti & Ravi S. Lankalapalli

  2. Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India

    D. K. Induja, A. R. S. Jesmina, Shanmughan Shamjith, Nagaraja Ingaladal, Kaustabh Kumar Maiti, B. S. Dileep Kumar & Ravi S. Lankalapalli

  3. Agro-Processing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, 695019, Kerala, India

    A. R. S. Jesmina & B. S. Dileep Kumar

Authors
  1. D. K. Induja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. R. S. Jesmina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manu M. Joseph
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shanmughan Shamjith
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nagaraja Ingaladal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kaustabh Kumar Maiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. S. Dileep Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ravi S. Lankalapalli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ravi S. Lankalapalli.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

41429_2023_638_MOESM1_ESM.docx

Isolation of two new stereochemical variants of streptophenazine by cocultivation of Streptomyces NIIST-D31, Streptomyces NIIST-D47, and Streptomyces NIIST-D63 strains in 3C2 combinations

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Induja, D.K., Jesmina, A.R.S., Joseph, M.M. et al. Isolation of two new stereochemical variants of streptophenazine by cocultivation of Streptomyces NIIST-D31, Streptomyces NIIST-D47, and Streptomyces NIIST-D63 strains in 3C2 combinations. J Antibiot 76, 567–578 (2023). https://doi.org/10.1038/s41429-023-00638-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-023-00638-7

Search

Advanced search

Quick links