Journal of Microbiology and Biotechnology

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

DOI QR Code

Induction of Fungal Secondary Metabolites by Co-Culture with Actinomycete Producing HDAC Inhibitor Trichostatins

  • Gwi Ja Hwang (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jongtae Roh (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Sangkeun Son (Antimicrobial Discovery Center, Department of Biology, Northeastern University) ;
  • Byeongsan Lee (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jun-Pil Jang (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jae-Seoun Hur (Korean Lichen Research Institute, Sunchon National University) ;
  • Young-Soo Hong (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jong Seog Ahn (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Sung-Kyun Ko (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Jae-Hyuk Jang (Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2023.01.12
  • Accepted : 2023.07.10
  • Published : 2023.11.28
Download PDF
⟨ Previous Next ⟩

Abstract

A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.

Keywords

Acknowledgement

This work was supported by the Korea Research Institute of Bioscience and Biotechnology (KRIBB) Research Initiative Program (KGM52922322 and KGM1222312) funded by the Ministry of Science ICT (MSIT) and the Basic Science Research Program (2021R1I1A2049704) of the Ministry of Education of the Republic of Korea. We thank the Korea Basic Science Institute, Ochang, Korea, for providing the NMR (700MHz) and HRESIMS data.

References

  1. Schueffler A, Anke T. 2014. Fungal natural products in research and development. Nat. Prod. Rep. 31: 1425-1448.
  2. Blackwell M. 2011. The fungi: 1, 2, 3 ... 5.1 million species? Am. J. Bot. 98: 426-438.
  3. Robey MT, Caesar LK, Drott MT, Keller NP, Kelleher NL. 2021. An interpreted atlas of biosynthetic gene clusters from 1,000 fungal genomes. Proc. Natl. Acad. Sci. USA 118 (19) e2020230118.
  4. Monciardini P, Iorio M, Maffioli S, Sosio M, Donadio S. 2014. Discovering new bioactive molecules from microbial sources. Microb. Biotechnol. 7: 209-220.
  5. Hautbergue T, Jamin EL, Debrauwer L, Puel O, Oswald IP. 2018. From genomics to metabolomics, moving toward an integrated strategy for the discovery of fungal secondary metabolites. Nat. Prod. Rep. 35: 147-173.
  6. Scherlach K, Hertweck C. 2009. Triggering cryptic natural product biosynthesis in microorganisms. Org. Biomol. Chem. 7: 1753-1760.
  7. Netzker T, Fischer J, Weber J, Mattern DJ, Konig CC, Valiante V, et al. 2015. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front. Microbiol. 6: 299.
  8. Keller NP. 2019. Fungal secondary metabolism: regulation, function and drug discovery. Nat. Rev. Microbiol. 17: 167-180.
  9. Bertrand S, Bohni N, Schnee S, Schumpp O, Gindro K, Wolfender JL. 2014. Metabolite induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery. Biotechnol. Adv. 32: 1180-1204.
  10. Arora D, Gupta P, Jaglan S, Roullier C, Grovel O, Bertrand S. 2020. Expanding the chemical diversity through microorganisms coculture: Current status and outlook. Biotechnol. Adv. 40: 107521.
  11. Williams RB, Henrikson JC, Hoover AR, Lee AE, Cichewicz RH. 2008. Epigenetic remodeling of the fungal secondary metabolome. Org. Biomol. Chem. 6: 1895-1897.
  12. Cherblanc FL, Davidson RW, Di Fruscia P, Srimongkolpithak N, Fuchter MJ. 2013. Perspectives on natural product epigenetic modulators in chemical biology and medicine. Nat. Prod. Rep. 30: 605-624.
  13. Son S, Ko SK, Jang M, Lee JK, Ryoo IJ, Lee JS, et al. 2015. Ulleungamides A and B, modified alpha,beta-dehydropipecolic acid containing cyclic depsipeptides from Streptomyces sp. KCB13F003. Org. Lett. 17: 4046-4049.
  14. Finnin MS, Donigian JR, Cohen A, Richon VM, Rifkind RA, Marks PA, et al. 1999. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 401: 188-193.
  15. Zutz C, Gacek A, Sulyok M, Wagner M, Strauss J, Rychli K. 2013. Small chemical chromatin effectors alter secondary metabolite production in Aspergillus clavatus. Toxins (Basel) 5: 1723-1741.
  16. Ohsumi K, Masaki T, Takase S, Watanabe M, Fujie A. 2014. AS2077715: a novel antifungal antibiotic produced by Capnodium sp. 339855. J. Antibiot. (Tokyo) 67: 707-711.
  17. Yu NH, Park SY, Kim JA, Park CH, Jeong MH, Oh SO, et al. 2018. Endophytic and endolichenic fungal diversity in maritime Antarctica based on cultured material and their evolutionary position among Dikarya. Fungal Syst. Evol. 2: 263-272.
  18. Kawamoto K, Yamazaki H, Ohte S, Masuma R, Uchida R, Tomoda H. 2011. Production of monapinones by fermentation of the dinapinone-producing fungus Penicillium pinophilum FKI-3864 in a seawater-containing medium. J. Antibiot. (Tokyo) 64: 503-508.
  19. Ohte S, Matsuda D, Uchida R, Nonaka K, Masuma R, Omura S, et al. 2011. Dinapinones, novel inhibitors of triacylglycerol synthesis in mammalian cells, produced by Penicillium pinophilum FKI-3864. J. Antibiot. (Tokyo) 64: 489-494.
  20. Uchida R, Ohte S, Kawamoto K, Yamazaki H, Kawaguchi M, Tomoda H. 2012. Structures and absolute stereochemistry of dinapinones A1 and A2, inhibitors of triacylglycerol synthesis, produced by penicillium pinophilum FKI-3864. J. Antibiot. (Tokyo) 65: 419-425.
  21. Kawaguchi M, Uchida R, Ohte S, Miyachi N, Kobayashi K, Sato N, et al. 2013. New dinapinone derivatives, potent inhibitors of triacylglycerol synthesis in mammalian cells, produced by Talaromyces pinophilus FKI-3864. J. Antibiot. (Tokyo) 66: 179-189.
  22. Kim J, Lee Y, Yu S. 1995. Sambutoxin-producing isolates of fusarium species and occurrence of sambutoxin in rotten potato tubers. Appl. Environ. Microbiol. 61: 3750-3751.
  23. Jayasinghe L, Abbas HK, Jacob MR, Herath WH, Nanayakkara NP. 2006. N-Methyl-4-hydroxy-2-pyridinone analogues from Fusarium oxysporum. J. Nat. Prod. 69: 439-442.
  24. Schmidt Y, Breit B. 2010. Direct assignment of the relative configuration in 1,3,n-methyl-branched carbon chains by 1H NMR spectroscopy. Org. Lett. 12: 2218-2221.
  25. Gupta GP, Massague J. 2006. Cancer metastasis: building a framework. Cell 127: 679-695.
  26. Hoshino S, Onaka H, Abe I. 2019. Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria. J. Ind. Microbiol. Biotechnol. 46: 363-374.