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:

Bisprenyl naphthoquinone and chlorinated calcimycin congener bearing thiazole ring from an actinomycete of the genus Phytohabitans

The Journal of Antibiotics volume 75, pages 542–551 (2022)Cite this article

Subjects

Abstract

A bisprenyl naphthoquinone, phytohabinone (1), and a calcimycin congener with unusual modifications, phytohabimicin (2), were isolated from the culture extract of Phytohabitans sp. RD003013. The structures of 1 and 2 were determined by NMR and MS analyses, and the absolute configuration of 2 was established by using electronic circular dichroism (ECD) calculation. The prenylation pattern of 1 was unprecedented among the known prenylated naphthoquinones. Compound 2 represents a spiroacetal core of polyketide origin substituted with a thiazole carboxylic acid and a dichrolopyrrole moiety, which is an unprecedented modification pattern in the known calcimycin family natural products. Remarkably, 2 showed moderate antimicrobial activity against a Gram-negative bacterium Ralstonia solanacearum while calcimycin was inactive. Additionally, 2 inhibits the migration of EC17 cancer cells at noncytotoxic concentrations.

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
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Saito S, Indo K, Oku N, Komaki H, Kawasaki M, Igarashi Y. Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes. Beilstein J Org Chem. 2021;17:2939–49.

    Article  CAS  Google Scholar 

  2. Lu S, Harunari E, Oku N, Igarashi Y. Trehangelin E, A bisacyl trehalose with plant growth promoting activity from a rare actinomycete Polymorphospora sp. RD064483. J Antibiot. 2022;75:296–300.

    Article  CAS  Google Scholar 

  3. Saito S, Oku N, Igarashi Y. Mycetoindole. An N-acyl dehydrotryptophan with plant growth inhibitory activity from an actinomycete of the genus Actinomycetospora. J Antibiot. 2022;75:44–7.

    Article  CAS  Google Scholar 

  4. Inahashi Y, Matsumoto A, Danbara H, Omura S, Takahashi Y. Phytohabitans suffuscus gen. nov., sp. nov., an actinomycete of the family Micromonosporaceae isolated from plant roots. Int J Syst Evol Microbiol. 2010;60:2652–8.

    Article  CAS  Google Scholar 

  5. Uchida R, Yokota S, Matsuda D, Matsumoto A, Iwamoto S, Onodera H, Takahashi Y, Tomoda H. Habiterpenol, a novel abrogator of bleomycin-induced G2 arrest in Jurkat cells, produced by Phytohabitans suffuscus 3787-5. J Antibiot. 2014;67:777–81.

    Article  CAS  Google Scholar 

  6. Komaki H, Tamura T. Polyketide synthase and nonribosomal peptide synthetase gene clusters in type strains of the genus Phytohabitans. Life. 2020;10:257.

    Article  CAS  Google Scholar 

  7. Saito S, Xiaohanyao Y, Zhou T, Nakajima-Shimada J, Tashiro E, Triningsih DW, Harunari E, Oku N, Igarashi Y. Phytohabitols A–C, δ-lactone-terminated polyketides from an actinomycete of the genus Phytohabitans. J Nat Prod. 2022;85:1697–703. https://doi.org/10.1021/acs.jnatprod.2c00137.

    Article  CAS  PubMed  Google Scholar 

  8. Kagamizono T, Hamaguchi T, Ando T, Sugawara K, Adachi T, Osada H. Phosphatoquinones A and B, novel tyrosine phosphatase inhibitors produced by Streptomyces sp. J Antibiot. 1999;52:75–80.

    Article  CAS  Google Scholar 

  9. Charan RD, Schlingmann G, Bernan VS, Feng X, Carter GT. Fumaquinone, a new prenylated naphthoquinone from Streptomyces fumanus. J Antibiot. 2005;58:271–4.

    Article  CAS  Google Scholar 

  10. Blin K, Shaw S, Kloosterman AM, Charlop-Powers Z, van Wezel GP, Medema MH, Weber T. AntiSMASH 6.0: Improving cluster detection and comparison capabilities. Nucleic Acids Res. 2021;49:W29–W35.

    Article  CAS  Google Scholar 

  11. Wu Q, Liang J, Lin S, Zhou X, Bai L, Deng Z, Wang Z. Characterization of the biosynthesis gene cluster for the pyrrole polyether antibiotic calcimycin (A23187) in Streptomyces chartreusis NRRL 3882. Antimicrob Agents Chemother. 2011;55:974–82.

    Article  CAS  Google Scholar 

  12. Duran-Sampedro G, Agarrabeitia AR, Garcia-Moreno I, Costela A, Bañuelos J, Arbeloa T, López Arbeloa I, Chiara JL, Ortiz MJ. Chlorinated BODIPYs: surprisingly efficient and highly photostable laser dyes. Eur J Org Chem. 2012;2012:6335–50.

    Article  CAS  Google Scholar 

  13. Lacerna NM, Miller BW, Lim AL, Tun JO, Robes J, Cleofas M, Lin Z, Salvador-Reyes LA, Haygood MG, Schmidt EW, Concepcion GP. Mindapyrroles A-C, Pyoluteorin analogues from a shipworm-associated bacterium. J Nat Prod. 2019;82:1024–8.

    Article  CAS  Google Scholar 

  14. Purdy TN, Kim MC, Cullum R, Fenical W, Moore BS. Discovery and biosynthesis of tetrachlorizine reveals enzymatic benzylic dehydrogenation via an ortho-quinone methide. J Am Chem Soc. 2021;143:3682–6.

    Article  CAS  Google Scholar 

  15. Mazzetti C, Ornaghi M, Gaspari E, Parapini S, Maffioli S, Sosio M, Donadio S. Halogenated spirotetronates from Actinoallomurus. J Nat Prod. 2012;75:1044–50.

    Article  CAS  Google Scholar 

  16. Murray LAM, Mckinnie SMK, Moore BS, George JH. Meroterpenoid natural products from Streptomyces bacteria-the evolution of chemoenzymatic syntheses. Nat Prod Rep. 2020;37:1334–66.

    Article  CAS  Google Scholar 

  17. Chaney MO, Demarco PV, Jones ND, Occolowitz JL. The Structure of A23187, a divalent cation ionophore. J Am Chem Soc. 1974;96:1932–3.

    Article  CAS  Google Scholar 

  18. David L, Kergomard A. Production by controlled biosynthesis of a novel ionophore antibiotic, cezomycin (demethylamino a23187). J Antibiot. 1982;35:1409–11.

    Article  CAS  Google Scholar 

  19. Liu CM, Chin M, Prosser BL, Palleroni NJ, Westley JW, Miller PA. X-14885A, a novel divalent cation ionophore produced by a streptomyces culture: discovery, fermentation, biological as well as ionophore properties and taxonomy of the producing culture. J Antibiot. 1983;36:1118–22.

    Article  CAS  Google Scholar 

  20. Cullen WP, Celmer WD, Chappel LR, Huang LH, Jefferson MT, Ishiguro M, Maeda H, Nishiyama S, Oscarson JR, Shibakawa R, Tone J. CP-61,405, a novel polycyclic pyrrolether antibiotic produced by Streptomyces routienii Huang sp. nov. J Ind Microbiol. 1988;2:349–57.

    Article  CAS  Google Scholar 

  21. Yaginuma S, Awata M, Muto N, Kinoshita K, Mizuno K. A novel polyether antibiotic, AC7230 (3-hydroxycezomycin or its stereoisomer). J Antibiot. 1987;40:239–41.

    Article  CAS  Google Scholar 

  22. Klika KD, Haansuu JP, Ovcharenko VV, Haahtela KK, Vuorela PM, Sillanpää R. Frankiamide: a structural revision to demethyl (C-11) cezomycin. Z fur Naturforsch-Sect B J Chem Sci. 2003;58:1210–15.

    Article  CAS  Google Scholar 

  23. MacroModel, Schrödinger, LLC: New York, NY, 2020.

  24. Gaussian 16, Revision C.01; Gaussian, Inc.: Wallingford, CT, 2016.

  25. Nakae K, Yoshimoto Y, Sawa T, Homma Y, Hamada M, Takeuchi T, Imoto M. Migrastatin, a new inhibitor of tumor cell migration from Streptomyces sp. MK929-43F1. Taxonomy, fermentation, isolation and biological activities. J Antibiot. 2000;53:1130–6.

    Article  CAS  Google Scholar 

  26. Sharma AR, Harunari E, Oku N, Matsuura N, Trianto A, Igarashi Y. Two antibacterial and PPARα/γ-agonistic unsaturated keto fatty acids from a coral-associated actinomycete of the genus Micrococcus. Beilstein J Org Chem. 2020;16:297–304.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

P388 cells were obtained from JCRB Cell Bank under accession code JCRB0017 (Lot. 06252002). This research was supported by JSPS KAKENHI grant no. JP19K05848 to Y. I.

Author information

Authors and Affiliations

  1. Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan

    Enjuro Harunari, Shunsuke Mae, Keisuke Fukaya, Daisuke Urabe & Yasuhiro Igarashi

  2. Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543, Japan

    Etsu Tashiro

Authors
  1. Enjuro Harunari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shunsuke Mae
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keisuke Fukaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Etsu Tashiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daisuke Urabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuhiro Igarashi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yasuhiro Igarashi.

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

Rights and permissions

Springer Nature or its licensor 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

Harunari, E., Mae, S., Fukaya, K. et al. Bisprenyl naphthoquinone and chlorinated calcimycin congener bearing thiazole ring from an actinomycete of the genus Phytohabitans. J Antibiot 75, 542–551 (2022). https://doi.org/10.1038/s41429-022-00559-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-022-00559-x

Search

Advanced search

Quick links