Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Hygrolansamycins A-D, O-Heterocyclic Macrolides from Streptomyces sp. KCB17JA11

  • Jang, Jun-Pil (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Byeongsan (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Heo, Kyung Taek (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Oh, Tae Hoon (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hyeok-Won (Biotechnology Process Engineering Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Ko, Sung-Kyun (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Hwang, Bang Yeon (College of Pharmacy, Chungbuk National University) ;
  • Jang, Jae-Hyuk (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Hong, Young-Soo (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2022.06.20
  • Accepted : 2022.09.01
  • Published : 2022.10.28
Download PDF
⟨ Previous Next ⟩

Abstract

Six ansamycin derivatives were isolated from the culture broth of Streptomyces sp. KCB17JA11, including four new hygrolansamycins A-D (1-4) and known congeners divergolide O (5) and hygrocin C (6). Compounds 1-5 featured an unusual six-membered O-heterocyclic moiety. The isolation workflow was guided by a Molecular Networking-based dereplication strategy. The structures of 1-4 were elucidated using NMR and HRESIMS experiments, and the absolute configuration was established by the Mosher's method. Compound 2 exhibited mild cytotoxicity against five cancer cell lines with IC50 values ranging from 24.60 ± 3.37 µM to 49.93 ± 4.52 µM.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant (2021M3H9A103743912), the KRIBB Research Initiative Program (KGM5292221 and KGM1222211) funded by the Ministry of Science ICT (MSIT) and the Basic Science Research Program (2021R1I1A204970412 and 2020R1I1A2068713) of the Ministry of Education of the Republic of Korea. We thank the Korea Basic Science Institute, Ochang, Korea, for providing the NMR (Bruker) and CD spectrum (Jasco).

References

  1. Kang Q, Shen Y, Bai L. 2012. Biosynthesis of 3,5-AHBA-derived natural products. Nat. Prod. Rep. 29: 243-263. https://doi.org/10.1039/C2NP00019A
  2. Floss HG. 2006. From ergot to ansamycins-45 years in biosynthesis. J. Nat. Prod. 69: 158-169. https://doi.org/10.1021/np058108l
  3. Cai P, Kong F, Ruppen ME, Glasier G, Carter GT. 2005. Hygrocins a and B, naphthoquinone macrolides from Streptomyces hygroscopicus. J. Nat. Prod. 68: 1736-1742. https://doi.org/10.1021/np050272l
  4. Ding L, Maier A, Fiebig HH, Gorls H, Lin WH, Peschel G et al. 2011. Divergolides A-D from a mangrove endophyte reveal an unparalleled plasticity in ansa-macrolide biosynthesis. Angew. Chem. Int. Ed. Engl. 50: 1630-1634. https://doi.org/10.1002/anie.201006165
  5. Lu C, Li Y, Deng J, Li S, Shen Y, Wang H et al. 2013. Hygrocins C-G, cytotoxic naphthoquinone ansamycins from gdmAI-disrupted Streptomyces sp. LZ35. J. Nat. Prod. 76: 2175-2179. https://doi.org/10.1021/np400474s
  6. Xu Z, Baunach M, Ding L, Peng H, Franke J, Hertweck C. 2014. Biosynthetic code for divergolide assembly in a bacterial mangrove endophyte. ChemBioChem 15: 1274-1279. https://doi.org/10.1002/cbic.201402071
  7. Nong XH, Tu ZC, Qi SH. 2020. Ansamycin derivatives from the marine-derived Streptomyces sp. SCSGAA 0027 and their cytotoxic and antiviral activities. Bioorg. Med. Chem. Lett. 30: 127168. https://doi.org/10.1016/j.bmcl.2020.127168
  8. Li SR, Zhao GS, Sun MW, He HG, Wang HX, Li YY et al. 2014. Identification and characterization of the biosynthetic gene cluster of divergolides from Streptomyces sp. W112. Gene 544: 93-99. https://doi.org/10.1016/j.gene.2014.04.052
  9. Ding L, Franke J, Hertweck C. 2015. Divergolide congeners illuminate alternative reaction channels for ansamycin diversification. Org. Biomol. Chem. 3: 1618-1623. https://doi.org/10.1039/C4OB02244K
  10. Lee JK, Jang JH, Park DJ, Kim CJ, Ahn JS, Hwang BY et al. 2017. Identification of new geldanamycin derivatives from unexplored microbial culture extracts using a MS/MS library. J. Antibiot. 70: 323-327. https://doi.org/10.1038/ja.2016.143
  11. Lee B, Son S, Lee JK, Jang M, Heo KT, Ko SK et al. 2020. Isolation of new streptimidone derivatives, glutarimide antibiotics from Streptomyces sp. W3002 using LC-MS-guided screening. J. Antibiot. 73: 184-188. https://doi.org/10.1038/s41429-019-0264-y
  12. Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD, Bruns N et al. 2013. Molecular networking as a dereplication strategy. J. Nat. Prod. 76: 1686-1699. https://doi.org/10.1021/np400413s
  13. Wang M, Carver JJ, Phelan VV, Sanchez LM, Garg N, Peng Y et al. 2016. Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking. Nat. Biotechnol. 34: 828-837. https://doi.org/10.1038/nbt.3597
  14. Demarque DP, Dusi RG, de Sousa FDM, Grossi SM, Silverio MRS, Lopes NP et al. 2020. Mass spectrometry-based metabolomics approach in the isolation of bioactive natural products. Sci. Rep. 10: 1051. https://doi.org/10.1038/s41598-020-58046-y
  15. Fiedler HP, Bruntner C, Bull AT, Ward AC, Goodfellow M, Potterat O et al. 2005. Marine actinomycetes as a source of novel secondary metabolites. Antonie Van. Leeuwenhoek 87: 37-42. https://doi.org/10.1007/s10482-004-6538-8
  16. Harvey AL. 2008. Natural products in drug discovery. Drug Discov. Today 13: 894-901. https://doi.org/10.1016/j.drudis.2008.07.004
  17. Zhao G, Li S, Guo Z, Sun M, Lu C. 2015. Overexpression of div8 increases the production and diversity of divergolides in Streptomyces sp. W112. RSC Adv. 5: 98209-98214. https://doi.org/10.1039/C5RA20083K