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:

Paranazzamides A and B, new cyclic dipeptides containing a C7-prenylated tryptophan, produced by pathogenic reptile fungi Paranannizziopsis sp. UH-21

The Journal of Antibiotics (2024)Cite this article

Subjects

Abstract

Two new cyclic dipeptides, paranazzamides A (1) and B (2) containing a C7-prenylated tryptophan, were isolated from a culture broth of snake fungal disease-isolate Paranannizziopsis sp. UH-21. This is the first report on the new secondary metabolites from Paranannizziopsis sp. The planar structures of 1 and 2 were elucidated using various spectroscopic techniques including MS and 1D/2D NMR. The absolute configuration of 1 was assigned by comparison with the synthesized compound. Compounds 1 and 2 exhibited no antifungal activity, no antibacterial activity, and no cytotoxic activity even at a concentration of 128 µg ml−1, whereas 1 and 2 exhibited amphotericin B potentiating activity against Candida auris in combination treatment.

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
Scheme 1
Scheme 2

Similar content being viewed by others

References

  1. Paré JA, Sigler L, Hunter DB, Summerbell RC, Smith DA, Machin KL. Cutaneous mycoses in chameleons caused by the Chrysosporium anamorph of Nannizziopsis vriesii (Apinis) Currah. J Zoo Wildl Med. 1997;28:443–53.

    PubMed  Google Scholar 

  2. Paré JA, Sigler L, Rypien KL, Gibas C-FC. Cutaneous mycobiota of captive squamate reptiles with notes on the scarcity of Chrysosporium anamorph of Nannizziopsis vriesii. J Herpetol Med Surg. 2003;13:10–15.

    Article  Google Scholar 

  3. Allender MC, Dreslik M, Wylie S, Phillips C, Wylie DB, Maddox C, et al. Chrysosporium sp. infection in eastern massasauga rattlesnakes. Emerg Infect Dis. 2011;17:2383–4.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Abarca ML, Martorell J, Castellá G, Ramis A, Cabañes FJ. Cutaneous hyalohyphomycosis caused by a Chrysosporium species related to Nannizziopsis vriesii in two green iguanas (Iguana iguana). Med Mycol. 2008;46:349–54.

    Article  CAS  PubMed  Google Scholar 

  5. Bowman MR, Paré JA, Sigler L, Naeser JP, Sladky KK, Hanley CS, et al. Deep fungal dermatitis in three inland bearded dragons (Pogona vitticeps) caused by the Chrysosporium anamorph of Nannizziopsis vriesii. Med Mycol. 2007;45:371–6.

    Article  PubMed  Google Scholar 

  6. Paré A, Coyle KA, Sigler L, Maas AK 3rd, Mitchell RL. Pathogenicity of the Chrysosporium anamorph of Nannizziopsis vriesii for veiled chameleons (Chamaeleo calyptratus). Med Mycol. 2006;44:25–31.

    Article  PubMed  Google Scholar 

  7. Sigler L, Hambleton S, Paré JA. Molecular characterization of reptile pathogens currently known as members of the chrysosporium anamorph of Nannizziopsis vriesii complex and relationship with some human-associated isolates. J Clin Microbiol. 2013;51:3338–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rajeev S, Sutton DA, Wickes BL, Miller DL, Giri D, Van Meter M, et al. Isolation and characterization of a new fungal species, Chrysosporium ophiodiicola, from a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta). J Clin Microbiol. 2009;47:1264–8.

    Article  CAS  PubMed  Google Scholar 

  9. Lorch JM, Lankton J, Werner K, Falendysz EA, McCurley K, Blehert DS. Experimental infection of snakes with Ophidiomyces ophiodiicola causes pathological changes that typify snake fungal disease. mBio. 2015;6:e01534–01515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gentry SL, Lorch JM, Lankton JS, Pringle A. Koch’s postulates: confirming Nannizziopsis guarroi as the cause of yellow fungal disease in Pogona vitticeps. Mycologia. 2021;113:1253–63.

    PubMed  Google Scholar 

  11. Díaz-Delgado J, Marrow JC, Flanagan JP, Bauer KL, Zhang M, Rodrigues-Hoffmann A, et al. Outbreak of Paranannizziopsis australasiensis infection in captive African bush vipers (Atheris squamigera). J Comp Pathol. 2020;181:97–102.

    Article  PubMed  Google Scholar 

  12. Lorch JM, Knowles S, Lankton JS, Michell K, Edwards JL, Kapfer JM, et al. Snake fungal disease: an emerging threat to wild snakes. Philos Trans R Soc Lond B Biol Sci. 2016;371:20150457.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Takami Y, Nam KO, Takaki Y, Kadekaru S, Hemmi C, Hosoya T, et al. First report of ophidiomycosis in Asia caused by Ophidiomyces ophiodiicola in captive snakes in Japan. J Vet Med Sci. 2021;83:1234–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bohacz J. Biodegradation of feather waste keratin by a keratinolytic soil fungus of the genus Chrysosporium and statistical optimization of feather mass loss. World J Microbiol Biotechnol. 2017;33:13.

    Article  PubMed  Google Scholar 

  15. Tanaka S, Shiomi S, Ishikawa H. Bioinspired indole prenylation reactions in water. J Nat Prod. 2017;80:2371–8.

    Article  CAS  PubMed  Google Scholar 

  16. Cui CB, Kakeya H, Okada G, Onose R, Ubukata M, Takahashi I, et al. Tryprostatins A and B, novel mammalian cell cycle inhibitors produced by Aspergillus fumigatus. J Antibiot. 1995;48:1382–4.

    Article  CAS  Google Scholar 

  17. Zhang DB, Yang ZD, Xue PH, Zhi KK, Shi Y, Wang MG. Two new cyclic dipeptides from Rhinocladiella sp. lgt-3, a fungal endophyte isolated from Tripterygium wilfordii hook. Nat Prod Res. 2014;28:1760–4.

    Article  CAS  PubMed  Google Scholar 

  18. Wang Y, Gloer JB, Scott JA, Malloch D. Terezines A-D: new amino acid-derived bioactive metabolites from the coprophilous fungus Sporormiella teretispora. J Nat Prod. 1995;58:93–99.

    Article  CAS  PubMed  Google Scholar 

  19. Asai T, Yamamoto T, Oshima Y. Histone deacetylase inhibitor induced the production of three novel prenylated tryptophan analogs in the entomopathogenic fungus, Torrubiella luteorostrata. Tetrahedron Lett. 2011;52:7042–5.

    Article  CAS  Google Scholar 

  20. Steffan N, Li SM. Increasing structure diversity of prenylated diketopiperazine derivatives by using a 4-dimethylallyltryptophan synthase. Arch Microbiol. 2009;191:461–6.

    Article  CAS  PubMed  Google Scholar 

  21. Liu X, Walsh CT. Characterization of cyclo-acetoacetyl-L-tryptophan dimethylallyltransferase in cyclopiazonic acid biosynthesis: substrate promiscuity and site directed mutagenesis studies. Biochemistry. 2009;48:11032–44.

    Article  CAS  PubMed  Google Scholar 

  22. Chakrabarti A, Sood P. On the emergence, spread and resistance of Candida auris: host, pathogen and environmental tipping points. J Med Microbiol. 2021;70:001318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Clinical and Laboratory Standards Institute. CLSI M27-A4. Reference method for broth dilution antifungal susceptibility testing of yeasts. 4th edn. Wayne, PA: Clinical and Laboratory Standards Institute; 2017.

  24. Fukuda T, Nagai K, Yagi A, Kobayashi K, Uchida R, Yasuhara T, et al. Nectriatide, a potentiator of amphotericin B activity from Nectriaceae sp. BF-0114. J Nat Prod. 2019;82:2673–81.

    Article  CAS  PubMed  Google Scholar 

  25. Yagi A, Uchida R, Kobayashi K, Tomoda H. Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by Pseudophialophora sp. BF-0158. J Antibiot. 2020;73:211–23.

    Article  CAS  Google Scholar 

  26. Clinical and Laboratory Standards Institute. CLSI M07. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 11th edn. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

  27. Hikima A, Asamizu S, Onaka H, Zhang H, Tomoda H, Koyama N. Kimidinomycin, a new antibiotic against Mycobacterium avium complex, produced by Streptomyces sp. KKTA-0263. J Antibiot. 2022;75:72–76.

    Article  CAS  Google Scholar 

  28. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ms. Honoka Kiguchi for her excellent assistance throughout this work and Ms. Noriko Sato (School of Pharmacy, Kitasato University) for NMR spectra measurements. This work was financially supported by JSPS KAKENHI Grant number JP21K15284 (Grant-in-Aid for Young Scientists) (KK), The Tokyo Biochemical Research Foundation (now Chugai Foundation for Innovative Drug Discovery Science: C-FINDs) (KK), The Research Foundation for Pharmaceutical Sciences (KK) and Kitasato University Research Grant for Young Researchers (KK).

Author information

Author notes

  1. These authors contributed equally: Keisuke Kobayashi, Rio Tejima.

Authors and Affiliations

  1. Department of Microbial Chemistry, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Keisuke Kobayashi, Rio Tejima, Satoru Shigeno, Hiroshi Tomoda & Taichi Ohshiro

  2. Medicinal Research Laboratories, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan

    Keisuke Kobayashi, Kenichiro Nagai, Reiko Seki, Satoru Shigeno & Taichi Ohshiro

  3. Department of Botany, National Museum of Nature and Science, 4-4-1 Amakubo, Tsukuba, Ibaraki, 305-0005, Japan

    Tsuyoshi Hosoya

  4. Laboratory of Veterinary Pathology, Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, Japan

    Yumi Une

Authors
  1. Keisuke Kobayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rio Tejima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenichiro Nagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Reiko Seki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tsuyoshi Hosoya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yumi Une
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Satoru Shigeno
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hiroshi Tomoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Taichi Ohshiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Taichi Ohshiro.

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 (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

Kobayashi, K., Tejima, R., Nagai, K. et al. Paranazzamides A and B, new cyclic dipeptides containing a C7-prenylated tryptophan, produced by pathogenic reptile fungi Paranannizziopsis sp. UH-21. J Antibiot (2024). https://doi.org/10.1038/s41429-024-00725-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41429-024-00725-3

Search

Advanced search

Quick links