Epigenetic Modifier Based Enhancement of Piperine Production in Endophytic Diaporthe sp. PF20

  • B. Jasim
  • Neethu Sahadevan
  • S. Chithra
  • Jyothis Mathew
  • E. K. Radhakrishnan
Research Article


Biodiversity and metabolite richness of endophytic fungi are highly fascinating. Some of them have even been reported to have the shared biosynthetic basis for the production of plant specific metabolites. However, only limited reports are there on enhancement of production of plant specific metabolites from endophytic fungi. In the study, endophytic Diaporthe sp. PF20 from Piper nigrum L. was identified to have the ability to produce piperine by liquid chromatography tandem mass spectroscopy. The isolate PF20 was further subjected to epigenetic treatment along with previously characterized piperine producing Colletotrichum sp. and Mycosphaerella sp. from the same plant. Very interestingly, use of histone deacetylase inhibitor suberohydroxamic acid enhanced the piperine production in PF20. Here, the epigenetic modulator mediated enhancement of phytochemical biosynthetic potential of endophytic fungi is novel in its approach. Hence the results of the study open up new avenues to maintain the biosynthetic competency of endophytic fungi, which is highly challenging. Even though piperine production has previously been reported from endophytic fungi, epigenetic modulator mediated multiplexing of this property as observed for PF20 is highly attractive. This is because, only this organism was found to be susceptible to epigenetic modulation based piperine enhancement among the selected isolates.


Diaporthe sp. Endophytic fungi Epigenetic modification Piperine Piper nigrum 



The present study was supported by Department of Biotechnology (DBT), Government of India under DBT-RGYI and DBT-MSUB support scheme (BT/PR4800/INF/22/152/2012 dated 23.03.2012) and Kerala State Council Science Technology and Environment (KSCSTE) under KSCSTE-SARD Programme. The authors also acknowledge Prof. C.T. Aravindakumar, Hon. Director and Mr. Dineep D., Scientific Assistant of the Inter-University Instrumentation Centre, Mahatma Gandhi University, Kottayam for the help and support for the LC–MS/MS analysis. They also acknowledge Dr. Jayachandran K, Associate Professor, School of Biosciences, Mahatma Gandhi University, PD Hills PO, Kottayam, India and Principal Investigator, Kerala Biotechnology Commission—Young Investigators Programme in Biotechnology (YIPB) programme for the help and support in performing the HPLC analysis.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest to publish this manuscript.


  1. 1.
    Aly AH, Debbab A, Kjer J, Proksch P (2010) Fungal endophytes from higher plants: a prolific source of phytochemicals and other bioactive natural products. Fungal Divers 41:1–16. CrossRefGoogle Scholar
  2. 2.
    Puri SC, Verma V, Amna T et al (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719. CrossRefPubMedGoogle Scholar
  3. 3.
    Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216. CrossRefPubMedGoogle Scholar
  4. 4.
    Zhao LF, Xu YJ, Ma ZQ et al (2013) Colonization and plant growth promoting characterization of endophytic Pseudomonas chlororaphis strain Zong1 isolated from Sophora alopecuroides root nodules. Braz J Microbiol 44:623–631. PubMedPubMedCentralGoogle Scholar
  5. 5.
    Garyali S, Kumar A, Reddy MS (2013) Taxol production by an endophytic fungus, fusarium redolens, isolated from himalayan yew. J Microbiol Biotechnol 23:1372–1380. CrossRefPubMedGoogle Scholar
  6. 6.
    Chithra S, Jasim B, Sachidanandan P et al (2014) Piperine production by endophytic fungus Colletotrichum gloeosporioides isolated from Piper nigrum. Phytomedicine 21:534–540. CrossRefPubMedGoogle Scholar
  7. 7.
    Chithra S, Jasim B, Anisha C et al (2014) LC-MS/MS based identification of piperine production by Endophytic Mycosphaerella sp. PF13 from Piper nigrum. Appl Biochem Biotechnol 173:30–35. CrossRefPubMedGoogle Scholar
  8. 8.
    Verma VC, Lobkovsky E, Gange AC et al (2011) Piperine production by endophytic fungus Periconia sp. isolated from Piper longum L. J Antibiot (Tokyo) 64:427–431. CrossRefGoogle Scholar
  9. 9.
    Cichewicz R (2012) Epigenetic regulation of secondary metabolite biosynthetic genes in fungi. In: Witzany G (eds) Biocommuniaction of fungi. Springer, Dordrecht, pp 57–69Google Scholar
  10. 10.
    Anisha C, Radhakrishnan EK (2015) Gliotoxin-producing endophytic Acremonium sp. from Zingiber officinale found antagonistic to soft rot pathogen Pythium myriotylum. Appl Biochem Biotechnol 175:3458–3467. CrossRefPubMedGoogle Scholar
  11. 11.
    Tamura K, Peterson D, Peterson N et al (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Sharma VK, Kumar J, Singh DK, Mishra A, Verma SK, Gond SK, Kumar A, Singh N, Kharwar RN (2017) Induction of cryptic and bioactive metabolites through natural dietary components in an endophytic fungus Colletotrichum gloeosporioides. Front Microbiol 8:1126CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Khajuria A, Thusa N, Zusthi U, Bedi KL (1997) Estimation of piperine in commercial ayurvedic formulations. J Indian Drugs 34:557–563Google Scholar
  14. 14.
    Lee SA, Hong SS, Han XH et al (2005) Piperine from the fruits of Piper longum with inhibitory effect on monoamine oxidase and antidepressant-like activity. Chem Pharm Bull 53:832–835. CrossRefPubMedGoogle Scholar
  15. 15.
    Mittal R, Gupta RL (2000) In vitro antioxidant activity of piperine. Methods Find Exp Clin Pharmacol 22:271–274CrossRefPubMedGoogle Scholar
  16. 16.
    Parmar VS, Jain SC, Bisht KS et al (1997) Phytochemistry of the genus Piper. Phytochemistry 46:597–673. CrossRefGoogle Scholar
  17. 17.
    Elsässer B, Krohn K, Flörke U et al (2005) X-ray structure determination, absolute configuration and biological activity of Phomoxanthone A. Eur J Org Chem 2005:4563–4570. CrossRefGoogle Scholar
  18. 18.
    Kobayashi H, Meguro S, Yoshimoto T, Namikoshi M (2003) Absolute structure, biosynthesis, and anti-microtubule activity of phomopsidin, isolated from a marine-derived fungus Phomopsis sp. Tetrahedron 59:455–459. CrossRefGoogle Scholar
  19. 19.
    Sharma VK, Kumar J, Singh DK, Mishra A, Gond SK, Verma SK, Kumar A, Singh G, Kharwar RN (2017) Induction of cryptic metabolite production through epigenetic tailoring in Colletotrichum gloeosporioides isolated from Syzygium cumini. In: Azevedo JL, Quecine MC (eds) Diversity and benefits of microorganisms from the tropics Sringer, pp 169–18 ( ISBN 978-3-319-55803-5
  20. 20.
    Cichewicz RH (2010) Epigenome manipulation as a pathway to new natural product scaffolds and their congeners. Nat Prod Rep 27:11–22. CrossRefPubMedGoogle Scholar
  21. 21.
    Shwab EK, Bok JW, Tribus M et al (2007) Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot Cell 6:1656–1664. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Chithra S, Jasim B, Mathew J, Radhakrishnan EK (2017) Endophytic Phomopsis sp. colonization in Oryza sativa was found to result in plant growth promotion and piperine production 437–446.

Copyright information

© The National Academy of Sciences, India 2018

Authors and Affiliations

  • B. Jasim
    • 1
  • Neethu Sahadevan
    • 1
  • S. Chithra
    • 1
  • Jyothis Mathew
    • 1
  • E. K. Radhakrishnan
    • 1
  1. 1.School of BiosciencesMahatma Gandhi University, PD Hills (PO)KottayamIndia

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