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.

  • Brief Communication
  • Published:

Novel macrolactam compound produced by the heterologous expression of a large cryptic biosynthetic gene cluster of Streptomyces rochei IFO12908

The Journal of Antibiotics volume 73, pages 171–174 (2020)Cite this article

Subjects

Abstract

In the course of our studies on the heterologous expression of giant biosynthetic genes, we discovered a novel cryptic biosynthetic gene cluster in Streptomyces rochei IFO12908. During our efforts to express biosynthetic genes using the host SUKA strain derived from Streptomyces avermitilis, a novel polyene macrolactam compound designated as JBIR-156 was produced. We report herein the cloning and heterologous expression of the JBIR-156 biosynthetic gene cluster, and the isolation, structure determination, and cytotoxic activity of this novel compound.

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

References

  1. Palazzolo AME, Simons CLW, Burke MD. The natural productome. Proc Natl Acad Sci USA. 2017;114:5564–6.

    Article  CAS  Google Scholar 

  2. Pye CR, Bertin MJ, Lokey RS, Gerwick WH, Linington RG. Retrospective analysis of natural products provides insights for future discovery trends. Proc Natl Acad Sci USA. 2017;114:5601–6.

    Article  CAS  Google Scholar 

  3. Doroghazi JR, et al. A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol. 2014;10:963–8.

    Article  CAS  Google Scholar 

  4. Gomez-Escribano JP, Bibb MJ. Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters. Micro Biotechnol. 2011;4:207–15.

    Article  CAS  Google Scholar 

  5. Komatsu M, Uchiyama T, Omura S, Cane DE, Ikeda H. Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism. Proc Natl Acad Sci USA. 2010;107:2646–51.

    Article  Google Scholar 

  6. Izumikawa M, et al. Novel thioviridamide derivative–JBIR-140: heterologous expression of the gene cluster for thioviridamide biosynthesis. J Antibiot. 2015;68:533–6.

    Article  CAS  Google Scholar 

  7. Ikeda H, Shin-ya K, Omura S. Genome mining of the Streptomyces avermitilis genome and development of genome-minimized hosts for heterologous expression of biosynthetic gene clusters. J Ind Microbiol Biotechnol. 2014;41:233–50.

    Article  CAS  Google Scholar 

  8. Nah HJ, Pyeon HR, Kang SH, Choi SS, Kim ES. Cloning and heterologous expression of a large-sized natural product biosynthetic gene cluster in Streptomyces species. Front Microbiol. 2017;8:394.

    Article  Google Scholar 

  9. Hashimoto T, et al. Biosynthesis of versipelostatin: identification of an enzyme-catalyzed [4 + 2]-cycloaddition required for macrocyclization of spirotetronate-containing polyketides. J Am Chem Soc. 2015;137:572–5.

    Article  CAS  Google Scholar 

  10. Zhang L, et al. Characterization of giant modular PKSs provides insight into genetic mechanism for structural diversification of aminopolyol polyketides. Angew Chem Int Ed. 2017;56:1740–5.

    Article  CAS  Google Scholar 

  11. Hashimoto T, et al. Biosynthesis of quinolidomicin, the largest known macrolide of terrestrial origin: identification and heterologous expression of a biosynthetic gene cluster over 200 kb. Org Lett. 2018;20:7996–9.

    Article  CAS  Google Scholar 

  12. Komatsu M, et al. Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites. ACS Synth Biol. 2013;2:384–96.

    Article  CAS  Google Scholar 

  13. Kim JH, Komatsu M, Shin-ya K, Omura S, Ikeda H. Distribution and functional analysis of the phosphopantetheinyl transferase superfamily in Actinomycetales microorganisms. Proc Natl Acad Sci USA. 2018;115:6828–33.

    Article  CAS  Google Scholar 

  14. Ogasawara Y, et al. Cloning, sequencing, and functional analysis of the biosynthetic gene cluster of macrolactam antibiotic vicenistatin in Streptomyces halstedii. Chem Biol. 2004;11:79–86.

    PubMed  CAS  Google Scholar 

  15. Jorgensen H, Degnes KF, Dikiy A, Fjaervik E, Klinkenberg G, Zotchev SB. Insights into the evolution of macrolactam biosynthesis through cloning and comparative analysis of the biosynthetic gene cluster for a novel macrocyclic lactam, ML-449. Appl Environ Microbiol. 2010;76:283–93.

    Article  CAS  Google Scholar 

  16. Low ZJ, Pang LM, Ding Y, Cheang QW, Hoang KLM, Tran HT, et al. Identification of a biosynthetic gene cluster for the polyene macrolactam sceliphrolactam in a Streptomyces strain isolated from mangrove sediment. Sci Rep. 2018;8:1594.

    Article  CAS  Google Scholar 

  17. Kudo F, Miyanaga A, Eguchi T. Biosynthesis of natural products containing β-amino acids. Nat Prod Rep. 2014;31:1056–73.

    Article  CAS  Google Scholar 

  18. Müller H, et al. German Patent DE 4231289. 1994.

  19. Peoples A, Zhang Q, Moore C, Lewis K, et al. US2009/0149395. 2009.

Download references

Acknowledgements

This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number JP17ae0101002 for KS.

Author information

Authors and Affiliations

  1. National Institute of Advanced Industrial Science and Technology, 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan

    Takuya Hashimoto, Reiko Ueoka, Noritaka Kagaya & Kazuo Shin-ya

  2. Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Koto-ku, Tokyo, 135-0064, Japan

    Ikuko Kozone & Junko Hashimoto

  3. Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Kunigami-gun, Okinawa, 904-0495, Japan

    Manabu Fujie & Noriyuki Sato

  4. Kitasato Institute for Life Sciences, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0373, Japan

    Haruo Ikeda

  5. Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

    Kazuo Shin-ya

  6. Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan

    Kazuo Shin-ya

Authors
  1. Takuya Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ikuko Kozone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junko Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reiko Ueoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Noritaka Kagaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manabu Fujie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Noriyuki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haruo Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kazuo Shin-ya
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kazuo Shin-ya.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

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

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hashimoto, T., Kozone, I., Hashimoto, J. et al. Novel macrolactam compound produced by the heterologous expression of a large cryptic biosynthetic gene cluster of Streptomyces rochei IFO12908. J Antibiot 73, 171–174 (2020). https://doi.org/10.1038/s41429-019-0265-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41429-019-0265-x

This article is cited by

Search

Advanced search

Quick links