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.

Dactylides A−C, three new bioactive 22-membered macrolides produced by Dactylosporangium aurantiacum

The Journal of Antibiotics (2023)Cite this article

Subjects

Abstract

Three new 22-membered polyol macrolides, dactylides A−C (1−3), were isolated from Dactylosporangium aurantiacum ATCC 23491 employing repeated chromatographic separations, and their structures were established based on detailed analysis of NMR and MS data. The relative configurations at the stereocenters were established via vicinal 1H–1H coupling constants, NOE correlations, and by application of Kishi’s universal NMR database. In order to get insights into the biosynthetic pathway of 1−3, the genome sequence of the producer strain D. aurantiacum was obtained and the putative biosynthetic gene cluster encoding their biosynthesis was identified through bioinformatic analysis using antiSMASH. Compounds 1−3 showed significant in-vitro antimycobacterial and cytotoxic activity.

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

$39.95

Learn more

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

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

Data availability

Data will be made available on request.

References

  1. Al-Fadhli AA, et al. Macrolides from rare actinomycetes: Structures and bioactivities. Int J Antimicrob Agents. 2022;59:106523. https://doi.org/10.1016/j.ijantimicag.2022.106523.

    Article  CAS  PubMed  Google Scholar 

  2. Elshahawi SI, Shaaban KA, Kharel MK, Thorson JS. A comprehensive review of glycosylated bacterial natural products. Chem Soc Rev. 2015;44:7591–697. https://doi.org/10.1039/C4CS00426D.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Onodera KI, Nakamura H, Oba Y, Ohizumi Y, Ojika M. Zooxanthellamide Cs: vasoconstrictive polyhydroxylated macrolides with the largest lactone ring size from a marine dinoflagellate of Symbiodinium sp. J Am Chem Soc. 2005;127:10406–11. https://doi.org/10.1021/ja050810g.

    Article  CAS  PubMed  Google Scholar 

  4. Cavalleri B, Arnone A, Di Modugno E, Nasini G, Goldstein BP. Structure and biological activity of lipiarmycin B. J Antibiot. 1988;41:308–15. https://doi.org/10.7164/antibiotics.41.308.

    Article  CAS  Google Scholar 

  5. Kurabachew M, et al. Lipiarmycin targets RNA polymerase and has good activity against multidrug-resistant strains of Mycobacterium tuberculosis. J Antimicrob Chemother. 2008;62:713–9. https://doi.org/10.1093/jac/dkn269.

    Article  CAS  PubMed  Google Scholar 

  6. Zhanel GG, Walkty AJ, Karlowsky JA. Fidaxomicin: A novel agent for the treatment of Clostridium difficile infection. Can J Infect Dis Med Microbiol. 2015;26:305–12. https://doi.org/10.1155/2015/934594.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Thiemann JE. A new species of the genus Amorphosporangium isolated from Italian soil. Mycopathol Mycol Appl. 1967;33:233–40. https://doi.org/10.1007/BF02088915.

    Article  CAS  PubMed  Google Scholar 

  8. Kobayashi Y, Tan CH, Kishi Y. Toward creation of a universal NMR database for stereochemical assignment: Complete structure of the desertomycin/oasomycin class of natural products. J Am Chem Soc. 2001;123:2076–8. https://doi.org/10.1021/ja004154q.

    Article  CAS  PubMed  Google Scholar 

  9. Blin K, et al. AntiSMASH 6.0: improving cluster detection and comparison capabilities. Nucleic Acids Res. 2021;49:W29–W35. https://doi.org/10.1093/nar/gkab335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Keatinge-Clay AT. A tylosin ketoreductase reveals how chirality is determined in polyketides. Chem Biol. 2007;14:898–908. https://doi.org/10.1016/j.chembiol.2007.07.009c.

    Article  CAS  PubMed  Google Scholar 

  11. Heinrichs MT, et al. Mycobacterium tuberculosis Strains H37Ra and H37Rv have equivalent minimum inhibitory concentrations to most antituberculosis drugs. Int J Mycobacteriol. 2018;7:156–61. https://doi.org/10.4103/ijmy.ijmy_33_18.

    Article  CAS  PubMed  Google Scholar 

  12. Paramita P, et al. Evaluation of potential anti‐cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells. IET Nanobiotech. 2018;12:727–32. https://doi.org/10.1049/iet-nbt.2017.0106.

    Article  Google Scholar 

  13. Shinde PB, et al. A non-immunosuppressive FK506 analogue with neuroregenerative activity produced from a genetically engineered Streptomyces strain. RSC Adv. 2015;5:6823–8. https://doi.org/10.1039/C4RA11907J.

    Article  CAS  Google Scholar 

  14. Helaly SE, et al. Langkolide, a 32-membered macrolactone antibiotic produced by Streptomyces sp. acta 3062. J Nat Prod. 2012;75:1018–24.

    Article  CAS  PubMed  Google Scholar 

  15. Rix U, Fischer C, Remsing LL, Rohr J. Modification of post-PKS tailoring steps through combinatorial biosynthesis. Nat Prod Rep. 2002;19:542–80. https://doi.org/10.1039/B103920M.

    Article  CAS  PubMed  Google Scholar 

  16. Lairson LL, Henrissat B, Davies GJ, Withers SG. Glycosyltransferases: structures, functions, and mechanisms. Annu Rev Biochem. 2008;77:521–55. https://doi.org/10.1146/annurev.biochem.76.061005.092322.

    Article  CAS  PubMed  Google Scholar 

  17. Kobayashi Y, Lee J, Tezuka K, Kishi Y. Toward creation of a universal NMR database for the stereochemical assignment of acyclic compounds: the case of two contiguous propionate units. Org Lett. 1999;1:2177–80. https://doi.org/10.1021/ol9903786.

    Article  CAS  PubMed  Google Scholar 

  18. Caradec T, et al. Dactylosporolides: Glycosylated macrolides from Dactylosporangium fulvum. J Nat Prod. 2022;85:2714–22. https://doi.org/10.1021/acs.jnatprod.2c00484.

    Article  CAS  PubMed  Google Scholar 

  19. Son S, et al. Catenulisporolides, glycosylated triene macrolides from the chemically underexploited actinomycete Catenulispora species. Org Lett. 2018;20:7234–8. https://doi.org/10.1021/acs.orglett.8b03160.

    Article  CAS  PubMed  Google Scholar 

  20. Fleury E, et al. Advances in the universal NMR database: toward the determination of the relative configurations of large polypropionates. Eur J Org Chem. 2009;2009:4992–5001. https://doi.org/10.1002/ejoc.200900616.

    Article  CAS  Google Scholar 

  21. Kobayashi Y, Tan CH, Kishi Y. Stereochemical assignment of the C21–C38 portion of the desertomycin/oasomycin class of natural products by using universal NMR databases: prediction. Angew Chem. 2000;112:4449–51. https://doi.org/10.1002/1521-3757(20001201)112:23<4449::AID-ANGE4449>3.0.CO;2-0.

    Article  Google Scholar 

  22. Kobayashi Y, Czechtizky W, Kishi Y. Complete stereochemistry of Tetrafibricin. Org Lett. 2003;5:93–96. https://doi.org/10.1021/ol0272895.

    Article  CAS  PubMed  Google Scholar 

  23. Seike H, Ghosh I, Kishi Y. Attempts to assemble a universal NMR database without synthesis of NMR database compounds. Org Lett. 2006;8:3861–4. https://doi.org/10.1021/ol061580t.

    Article  CAS  PubMed  Google Scholar 

  24. Zheng J, Taylor CA, Piasecki SK, Keatinge-Clay AT. Structural and functional analysis of A-type ketoreductases from the amphotericin modular polyketide synthase. Structure. 2010;18:913–22. https://doi.org/10.1016/j.str.2010.04.015.

    Article  CAS  PubMed  Google Scholar 

  25. Kwan DH, Schulz F. The stereochemistry of complex polyketide biosynthesis by modular polyketide synthases. Molecules. 2011;16:6092–115. https://doi.org/10.3390/molecules16076092.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Zhang P, Zhang Z, Zhang L, Wang J, Wu C. Glycosyltransferase GT1 family: Phylogenetic distribution, substrates coverage, and representative structural features. Comput Struct Biotechnol J. 2020;18:1383–90. https://doi.org/10.1016/j.csbj.2020.06.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Scientific and Engineering Research Board (SERB), Department of Science and Technology [ECRA/2016/000788 and EEQ/2016/000268]; and Council of Scientific and Industrial Research (CSIR), New Delhi [MLP/0027]. Yedukondalu Nalli acknowledges Scientific and Engineering Research Board (SERB) for providing National Postdoctoral Fellowship (N-PDF). Sanju Singh acknowledges Council of Scientific and Industrial Research (CSIR) for JRF and SRF fellowship. Padmaja D. Wakchaure acknowledges CSIR, New Delhi, India, for the GATE-SRF fellowship. Pankaj Kumar acknowledges Department of Biotechnology (DBT) for providing JRF and SRF fellowship. Central Instrumentation facility CSIR-CSMCRI is acknowledged for acquiring MS, FT-IR, CD, and NMR spectral data.

Author information

Author notes

  1. These authors contributed equally: Pankaj Kumar, Yedukondalu Nalli

Authors and Affiliations

  1. Natural Products & Green Chemistry Division, CSIR-Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI), Council of Scientific and Industrial Research (CSIR), Bhavnagar, Gujarat, 364002, India

    Pankaj Kumar, Yedukondalu Nalli, Sanju Singh, Vishal A. Ghadge & Pramod B. Shinde

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

    Pankaj Kumar, Sanju Singh, Padmaja D. Wakchaure, Vishal A. Ghadge, Bishwajit Ganguly & Pramod B. Shinde

  3. Computation and Simulation Unit, Analytical and Environmental Science Division and Centralized Instrument Facility, CSIR-Central Salt and Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364002, India

    Padmaja D. Wakchaure & Bishwajit Ganguly

  4. Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu, 603203, India

    Ravi Gor & Satish Ramalingam

  5. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea

    Eunji Kim & Yeo Joon Yoon

  6. Department of Bacteriology, National Institute for Research in Tuberculosis, ICMR, Sathyamoorty road, Chetpet, Chennai, 600031, Tamil Nadu, India

    V. N. Azger Dusthackeer

Authors
  1. Pankaj Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yedukondalu Nalli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanju Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Padmaja D. Wakchaure
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ravi Gor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vishal A. Ghadge
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eunji Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Satish Ramalingam
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. V. N. Azger Dusthackeer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yeo Joon Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bishwajit Ganguly
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Pramod B. Shinde
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pramod B. Shinde.

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

Kumar, P., Nalli, Y., Singh, S. et al. Dactylides A−C, three new bioactive 22-membered macrolides produced by Dactylosporangium aurantiacum. J Antibiot (2023). https://doi.org/10.1038/s41429-023-00632-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41429-023-00632-z

Search

Advanced search

Quick links