Skip to main content

Thank you for visiting 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.

Prodigiosin R3, a new multicyclic prodigiosin formed by prodigiosin cyclization genes in the roseophilin producer


The rph gene cluster for prodigiosin biosynthesis has been identified in Streptomyces griseoviridis 2464-S5, which produces cyclic prodigiosin derivatives including roseophilin (2), prodigiosin R1 (3) and prodigiosin R2 (4). A new cyclic prodigiosin, prodigiosin R3 (1), was produced by the redG redP double disruptant of Streptomyces coelicolor M511 expressing four cyclization gene candidates (rphG, rphG2, rphG3 and rphG4) in the rph cluster. The same compound was isolated from Streptomyces griseoviridis 2464-S5. The molecular formula of 1 was established as C27H33N3O by ESI and FAB mass spectrometry. The structure was determined to be a multicyclic prodigiosin with three alkyl linkages by NMR spectroscopic analysis. Prodigiosin R3 (1) showed cytotoxicity against HeLa human cervical carcinoma cells and HT1080 human fibrosarcoma cells with IC50s of 2.1 µM and 3.2 µM, respectively.

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

Access options

Rent or buy this article

Get just this article for as long as you need it


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

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


  1. Stankovic N, Senerovic L, Ilic-Tomic T, Vasiljevic B, Nikodinovic-Runic J. Properties and applications of undecylprodigiosin and other bacterial prodigiosins. J Appl Microbiol Biotechnol. 2014;98:3841–58.

    Article  CAS  Google Scholar 

  2. Hayakawa Y, Kawakami K, Seto H. Structure of a new antibiotic, roseophilin. Tetrahedron Lett. 1992;33:2701–4.

    Article  Google Scholar 

  3. Kawasaki T, Sakurai F, Hayakawa Y. A prodigiosin from the roseophilin producer Streptomyces griseoviridis. J Nat Prod. 2008;71:1265–7.

    Article  CAS  Google Scholar 

  4. Kimata S, Matsuda T, Suizu Y, Hayakawa Y. Prodigiosin R2, a new prodigiosin from the roseophilin producer Streptomyces griseoviridis 2464-S5. J Antibiot. 2018;71:393–6.

    Article  CAS  Google Scholar 

  5. Kawasaki T, Sakurai F, Nagatsuka S, Hayakawa Y. Prodigiosin biosynthesis gene cluster in the roseophilin producer Streptomyces griseoviridis. J Antibiot. 2009;62:271–6.

    Article  CAS  Google Scholar 

  6. Mo S, Sydor PK, Corre C, Alhamadsheh MM, Stanley AE, Haynes SW, Song L, Reynolds KA, Challis GL. Elucidation of the Streptomyces coelicolor pathway to 2-undecylpyrrole, a key intermediate in undecylprodiginine and streptorubin B biosynthesis. Chem Biol. 2008;15:137–48.

    Article  CAS  Google Scholar 

  7. Kimata S, Izawa M, Kawasaki T, Hayakawa Y. Identification of a prodigiosin cyclization gene in the roseophilin producer and production of a new cyclized prodigiosin in a heterologous host. J Antibiot. 2017;70:196–9.

    Article  CAS  Google Scholar 

  8. Summers MF, Marzilli LG, Bax A. Complete 1H and 13C assignments of coenzyme B12 through the use of new two-dimensional NMR experiments. J Am Chem Soc. 1986;108:4285–94.

    Article  CAS  Google Scholar 

  9. Bax A, Summers MF. 1H and 13C assignments from sensitivity enhanced detection of heteronuclear multiple-bond connectivity by multiple quantum NMR. J Am Chem Soc. 1986;108:2093–4.

    Article  CAS  Google Scholar 

  10. Sydor PK, Barry SM, Odulate OM, Gomez FB, Haynes SW, Corre C, Song L, Chalis GL. Regio- and stereodivergent antibiotic oxidative carbocyclizations catalyzed by Rieske oxygenase-like enzymes. Nat Chem. 2011;3:388–92.

    Article  CAS  Google Scholar 

  11. Kieser T, Bibb MJ, Buttner MJ, Chater KF, Hopwood DA. Practical Streptomyces Genetics (John Innes Foundation, Norwich, UK, 2000).

  12. Sambrook JE, Russell DW. Molecular Cloning: A Laboratory Manual, 2nd Ed. (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1989).

Download references


We thank Prof. M. Bibb, John Innes Centre, for providing S. coelicolor M511. We also thank F. Hasegawa, Tokyo University of Science, for assistance with mass spectrometry.


This work was supported in part by a Grant-in-Aid for Early-Career Scientists 21K14775 (to SK), Japan Society for the Promotion of Science (JSPS).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Yoichi Hayakawa.

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

Verify currency and authenticity via CrossMark

Cite this article

Kimata, S., Matsuda, T., Kawasaki, T. et al. Prodigiosin R3, a new multicyclic prodigiosin formed by prodigiosin cyclization genes in the roseophilin producer. J Antibiot 76, 14–19 (2023).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


Quick links