Skip to main content
SpringerLink
Log in

Activation of Cryptic Secondary Metabolite Biosynthesis in Bamboo Suspension Cells by a Histone Deacetylase Inhibitor

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Plants have evolved a diverse array of secondary metabolite biosynthetic pathways. Undifferentiated plant cells, however, tend to biosynthesize secondary metabolites to a lesser extent and sometimes not at all. This phenomenon in cultured cells is associated with the transcriptional suppression of biosynthetic genes due to epigenetic alterations, such as low histone acetylation levels and/or high DNA methylation levels. Here, using cultured cells of bamboo (Bambusa multiplex; Bm) as a model system, we investigated the effect of histone deacetylase (HDAC) inhibitors on the activation of cryptic secondary metabolite biosynthesis. The Bm suspension cells cultured in the presence of an HDAC inhibitor, suberoyl bis-hydroxamic acid (SBHA), exhibited strong biosynthesis of some compounds that are inherently present at very low levels in Bm cells. Two major compounds induced by SBHA were isolated and were identified as 3-O-p-coumaroylquinic acid (1) and 3-O-feruloylquinic acid (2). Their productivities depended on the type of basal culture medium, initial cell density, and culture period, as well as the SBHA concentration. The biosynthesis of these two compounds was also induced by another HDAC inhibitor, trichostatin A. These results demonstrate the usefulness of HDAC inhibitors to activate cryptic secondary metabolite biosynthesis in cultured plant cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data Availability

Data that support the findings of this study and the materials used are available from the corresponding author upon reasonable request.

Code Availability

Not applicable.

References

  1. Tulp, M., & Bohlin, L. (2005). Rediscovery of known natural compounds: Nuisance or goldmine? Bioorganic & Medicinal Chemistry, 13, 5274–5282.

    Article  CAS  Google Scholar 

  2. Hartmann, T. (2007). From the waste products to ecochemicals: Fifty years research of plant secondary metabolism. Phytochemistry, 68, 2831–2846.

    Article  CAS  Google Scholar 

  3. Pichersky, E., & Lewinsohn, E. (2011). Convergent evolution in plant specialized metabolism. Annual Review of Plant Biology, 62, 549–566.

    Article  CAS  Google Scholar 

  4. Balandrin, M. F., Klocke, J. A., Wurtele, E. S., & Bollinger, W. H. (1985). Natural plant chemicals: Sources of industrial and medicinal materials. Science, 228, 1154–1160.

    Article  CAS  Google Scholar 

  5. Hines, P. J., & Zahn, L. M. (2012). Green pathways. Science, 336, 1657.

    Article  CAS  Google Scholar 

  6. Chandran, H., Meena, M., Barupal, T., & Sharma, K. (2020). Plant tissue culture as a perpetual source for production of industrially important bioactive compounds. Biotechnology Reports, 26, e00450.

    Article  PubMed  Google Scholar 

  7. Marchev, A. S., Yordanova, Z. P., & Georgiev, M. I. (2020). Green (cell) factories for advanced production of plant secondary metabolites. Critical Reviews in Biotechnology, 40, 443–458.

    Article  CAS  Google Scholar 

  8. Atanasov, A. G., Waltenberger, B., Pferschy-Wenzig, E.-M., Linder, T., Wawrosch, C., Uhrin, P., Temml, V., Wang, L., Schwaiger, S., Heiss, E. H., Rollinger, J. M., Schuster, D., Breuss, J. M., Bochkov, V., Mihovilovic, M. D., Kopp, B., Bauer, R., Dirsch, V. M., & Stuppner, H. (2015). Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology Advances, 33, 1582–1614.

    Article  CAS  PubMed  Google Scholar 

  9. Kolewe, M. E., Gaurav, V., & Roberts, S. C. (2008). Pharmaceutically active natural product synthesis and supply via plant cell culture technology. Molecular Pharmaceutics, 5, 243–256.

    Article  CAS  Google Scholar 

  10. Miralpeix, B., Rischer, H., Häkkinen, S. T., Ritala, A., Seppänen-Laakso, T., Oksman-Caldentey, K.-M., Capell, T., & Christou, P. (2013). Metabolic engineering of plant secondary products: Which way forward? Current Pharmaceutical Design, 19, 5622–5639.

    Article  CAS  Google Scholar 

  11. Yazaki, K. (2017). Lithospermum erythrorhizon cell cultures: Present and future aspects. Plant Biotechnology, 34, 131–142.

    Article  CAS  PubMed  Google Scholar 

  12. Isah, T., Umar, S., Mujib, A., Sharma, M. P., Rajasekharan, P. E., Zafar, N., & Frukh, A. (2018). Secondary metabolism of pharmaceuticals in the plant in vitro cultures: Strategies, approaches, and limitations to achieving higher yield. Plant Cell Tissue and Organ Culture, 132, 239–265.

    Article  CAS  Google Scholar 

  13. Smulders, M. J. M., & de Klerk, G. J. (2011). Epigenetics in plant tissue culture. Plant Growth Regulation, 63, 137–146.

    Article  CAS  Google Scholar 

  14. Vervoort, H., Drašković, M., & Crews, P. (2011). Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: Isolation of EGM-556, a cyclodepsipeptide, from Microascus sp. Organic Letters, 13, 410–413.

    Article  CAS  PubMed  Google Scholar 

  15. Asai, T., Chung, Y. M., Sakurai, H., Ozeki, T., Chang, F.-R., Yamashita, K., & Oshima, Y. (2012). Tenuipyrone, a novel skeletal polyketide from the entomopathogenic fungus, Isaria tenuipes, cultivated in the presence of epigenetic modifiers. Organic Letters, 14, 513–515.

    Article  CAS  PubMed  Google Scholar 

  16. Asai, T., Yamamoto, T., & Oshima, Y. (2012). Aromatic polyketide production in Cordyceps indigotica, an entomopathogenic fungus, induced by exposure to a histone deacetylase inhibitor. Organic Letters, 14, 2006–2009.

    Article  CAS  PubMed  Google Scholar 

  17. Asai, T., Yamamoto, T., Chung, Y.-M., Chang, F.-R., Wu, Y.-C., Yamashita, K., & Oshima, Y. (2012). Aromatic polyketide glycosides from an entomopathogenic fungus Cordyceps indigotica. Tetrahedron Letters, 53, 277–280.

    Article  CAS  Google Scholar 

  18. Asai, T., Yamamoto, T., Shirata, N., Taniguchi, T., Monde, K., Fujii, I., Gomi, K., & Oshima, Y. (2013). Structurally diverse chaetophenol productions induced by chemically mediated epigenetic manipulation of fungal gene expression. Organic Letters, 15, 3346–3349.

    Article  CAS  PubMed  Google Scholar 

  19. Toghueo, R. M. K., Sahal, D., & Boyom, F. F. (2020). Recent advances in inducing endophytic fungal specialized metabolites using small molecule elicitors including epigenetic modifiers. Phytochemistry, 174, 112338.

    Article  CAS  PubMed  Google Scholar 

  20. Ogita, S. (2005). Callus and cell suspension culture of bamboo plant Phyllostachys nigra. Plant Biotechnology, 22, 119–125.

  21. Ogita, S., Kikuchi, N., Nomura, T., & Kato, Y. (2011). A practical protocol for particle bombardment-mediated transformation of Phyllostachys bamboo suspension cells. Plant Biotechnology, 28, 43–50.

    Article  Google Scholar 

  22. Ogita, S., Nomura, T., Kishimoto, T., & Kato, Y. (2012). A novel xylogenic suspension culture model for exploring lignification in Phyllostachys bamboo. Plant Methods, 8, 40.

    Article  CAS  PubMed  Google Scholar 

  23. Ogita, S., & Sasamoto, H. (2017). In vitro bioassay of allelopathy in four bamboo species; Bambusa multiplex, Phyllostachys bambusoides, P. nigra, Sasa kurilensis, using sandwich method and protoplast co-culture method with digital image analysis. American Journal of Plant Sciences, 8, 1699–1710.

    Article  CAS  Google Scholar 

  24. Nomura, T., Shiozawa, M., Ogita, S., & Kato, Y. (2013). Occurrence of hydroxycinnamoylputrescines in xylogenic bamboo suspension cells. Plant Biotechnology, 30, 447–453.

    Article  CAS  Google Scholar 

  25. Murashige, T., & Skoog, F. (1962). A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiologia Plantarum, 15, 473–479.

    Article  CAS  Google Scholar 

  26. Onkokesung, N., Gaquerel, E., Kotkar, H., Kaur, H., Baldwin, I. T., & Galis, I. (2012). MYB8 controls inducible phenolamide levels by activating three novel hydroxycinnamoyl-coenzyme A:polyamine transferases in Nicotiana attenuate. Plant Physiology, 158, 389–407.

  27. Abrankó, L., & Clifford, M. N. (2017). An unambiguous nomenclature for the acyl-quinic acids commonly known as chlorogenic acids. Journal of Agricultural and Food Chemistry, 65, 3602–3608.

    Article  Google Scholar 

  28. Clifford, M. N., Jaganath, I. B., Ludwig, I. A., & Crozier, A. (2017). Chlorogenic acids and the acyl-quinic acids: Discovery, biosynthesis, bioavailability and bioactivity. Natural Product Reports, 34, 1391–1421.

    Article  CAS  Google Scholar 

  29. Ortiz, A. L. G., Berti, F., Navarini, L., Monteiro, A., Resmini, M., & Forzato, C. (2017). Synthesis of p-coumaroylquinic acids and analysis of their interconversion. Tetrahedron: Asymmetry, 28, 419–427.

    Article  Google Scholar 

  30. Jin, S., & Yoshida, M. (2005). Accumulation of 3-O-feruloylquinic acid induced by low temperature in wheat. Cryobiology and Cryotechnology, 2, 57–62.

    Google Scholar 

  31. Keller, N. P. (2019). Fungal secondary metabolism: Regulation, function and drug discovery. Nature Reviews Microbiology, 17, 167–180.

    Article  CAS  PubMed  Google Scholar 

  32. Kliebenstein, D. J., & Osbourn, A. (2012). Making new molecules – evolution of pathways for novel metabolites in plants. Current Opinion in Plant Biology, 15, 415–423.

    Article  CAS  Google Scholar 

  33. Wisecaver, J. H., Borowsky, A., Tzin, V., Jander, G., Kliebenstein, D. J., & Rokas, A. (2017). A global coexpression network approach for connecting genes to specialized metabolic pathways in plants. The Plant Cell, 29, 944–959.

    Article  CAS  PubMed  Google Scholar 

  34. Nomura, T., Ishihara, A., Yanagita, R. C., Endo, T. R., & Iwamura, H. (2004). Three genomes differentially contribute to the biosynthesis of benzoxazinones in hexaploid wheat. Proceedings of the National Academy of Sciences of the United States of America, 102, 16490–16495.

  35. Sue, M., Nakamura, C., & Nomura, T. (2011). Dispersed benzoxazinone gene cluster: Molecular characterization and chromosomal localization of glucosyltransferase and glucosidase genes in wheat and rye. Plant Physiology, 157, 985–997.

    Article  CAS  PubMed  Google Scholar 

  36. Petersen, M. (2016). Hydroxycinnamoyltransferases in plant metabolism. Phytochemistry Reviews, 15, 699–727.

    Article  CAS  Google Scholar 

  37. Kitaoka, N., Nomura, T., Ogita, S., & Kato, Y. (2020). Bioproduction of glucose conjugates of 4-hydroxybenzoic and vanillic acids using bamboo cells transformed to express bacterial 4-hydroxycinnamoyl-CoA hydratase/lyase. Journal of Bioscience and Bioengineering, 130, 89–97.

    Article  CAS  PubMed  Google Scholar 

  38. Kitaoka, N., Nomura, T., Ogita, S., & Kato, Y. (2021). Bioproduction of 4-vinylphenol and 4-vinylguaiacol β-primeverosides using transformed bamboo cells expressing bacterial phenolic acid decarboxylase. Applied Biochemistry and Biotechnology, 193, 2061–2075.

  39. Matzke, A. J., & Matzke, M. A. (1998). Position effects and epigenetic silencing of plant transgenes. Current Opinion in Plant Biology, 1, 142–148.

    Article  CAS  PubMed  Google Scholar 

  40. Kooter, J. M., Matzke, M. A., & Meyer, P. (1999). Listening to the silent genes: Transgene silencing, gene regulation and pathogen control. Trends in Plant Science, 4, 340–347.

    Article  CAS  Google Scholar 

  41. Nomura, T., Ogita, S., & Kato, Y. (2018). Rational metabolic-flow switching for the production of exogenous secondary metabolites in bamboo suspension cells. Scientific Reports, 8, 13203.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We appreciate valuable discussions with Dr. Naoki Kitaoka (Toyama Prefectural University; currently Hokkaido University). We thank Mr. Yuta Murai (Toyama Prefectural University) for his technical assistance. We thank Jennifer Smith, PhD, from Edanz Group (https://en-author-services.edanz.com/ac), for editing a draft of this manuscript.

Funding

This work was supported in part by JSPS KAKENHI grant nos. JP18K05463 (to TN) and JP16K07697 (to YK).

Author information

Authors and Affiliations

  1. Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan

    Taiji Nomura, Akari Yoneda & Yasuo Kato

  2. Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 5562 Nanatsukacho, Shobara, Hiroshima, 727-0023, Japan

    Shinjiro Ogita

Authors
  1. Taiji Nomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akari Yoneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shinjiro Ogita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuo Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

T.N. designed the research. T.N. and A.Y. performed experiments. T.N., A.Y., S.O., and Y.K. analyzed data. T.N. wrote the paper.

Corresponding author

Correspondence to Taiji Nomura.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

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

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 407 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nomura, T., Yoneda, A., Ogita, S. et al. Activation of Cryptic Secondary Metabolite Biosynthesis in Bamboo Suspension Cells by a Histone Deacetylase Inhibitor. Appl Biochem Biotechnol 193, 3496–3511 (2021). https://doi.org/10.1007/s12010-021-03629-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-021-03629-2

Keywords

Search

Navigation