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Biotechnology Letters

, Volume 41, Issue 12, pp 1439–1449 | Cite as

Epigenetic modification enhances ergot alkaloid production of Claviceps purpurea

  • Jing-Jing Chen
  • Meng-Yao Han
  • Ting Gong
  • Yun-Ming Qiao
  • Jin-Ling Yang
  • Ping ZhuEmail author
Original Research Paper

Abstract

Objective

To enhance ergot alkaloid production of Claviceps purpurea Cp-1 strain by epigenetic modification approach.

Results

The chemical epigenetic modifiers were screened to promote ergot alkaloid production of the Cp-1 strain. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) was found to significantly enhance the alkaloid productivity of the strain. Particularly, the titers of total ergot alkaloids were gradually increased with the increase of SAHA concentration in the fermentation medium, and the highest production of ergot alkaloids could be achieved at the concentration of 500 μM SAHA. Specially, the titers of ergometrine and total ergot alkaloids were as high as 95.4 mg/L and 179.7 mg/L, respectively, which were twice of those of the control. Furthermore, the mRNA expression levels of the most functional genes in the ergot alkaloid synthesis (EAS) gene cluster were up-regulated under SAHA treatment. It was proposed that SAHA might increase histone acetylation in the EAS gene cluster region in the chromosome, which would loosen the chromosome structure, and subsequently up-regulate the mRNA expression levels of genes involved in the biosynthesis of ergot alkaloids, thereby resulting in the markedly increase in the production of ergot alkaloids.

Conclusions

The ergot alkaloid production by the C. purpurea Cp-1 strain can be effectively increased by the application of histone deacetylase inhibitor. Our work provides a reference for using the chemical epigenetic modifiers to improve SM production in other fungi.

Keywords

Ergot alkaloid Claviceps purpurea Biosynthetic pathway Epigenetic Gene expression 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant no 81603002), CAMS Innovation Fund for Medical Sciences (Grant Nos. CIFMS-2016-I2M-2-002 and CIFMS-2017-I2M-4-004), and the Drug Innovation Major Project (Grant No. 2018ZX09711001-006).

Supporting information

Supplementary Figure 1—The mycelium wet weight of Cp-1 strain in fermentation medium supplemented with different HDACi and HATi for 14 days.

Supplementary Figure 2—The mycelium wet weight of Cp-1 strain in fermentation medium supplemented with different concentrations of SAHA for 14 days.

Supplementary Figure 3—The mycelium wet weight of Cp-1 strain in fermentation medium supplemented with different concentrations of sodium valproate for 14 days.

Supplementary Figure 4—Volcano plot for all DEGs, which plotted FDR against FC. Each point represents a gene, the green dot and red dot represent significantly up-regulated and down-regulated genes, respectively. The black dot represents a gene that does not show significant difference.

Supplementary Figure 5—Functional annotation of DEGs based on cluster of orthologous groups of proteins (COG) categorization.

Supplementary Figure 6—Functional annotation of DEGs based on gene ontology (GO) categorization. GO analysis was performed for three main categories (cellular component, molecular function and biological process).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10529_2019_2750_MOESM1_ESM.docx (785 kb)
Electronic supplementary material 1 (DOCX 785 kb)

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Jing-Jing Chen
    • 1
  • Meng-Yao Han
    • 1
  • Ting Gong
    • 1
  • Yun-Ming Qiao
    • 1
  • Jin-Ling Yang
    • 1
  • Ping Zhu
    • 1
    Email author
  1. 1.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina

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