Biotechnology Letters

, Volume 37, Issue 12, pp 2481–2487 | Cite as

A novel terpenoid indole alkaloid derived from catharanthine via biotransformation by suspension-cultured cells of Catharanthus roseus

Original Research Paper
First Online:
Received:
Accepted:

Abstract

Objective

Although catharanthine (1) is well known as a biosynthetic precursor of the anticancer alkaloid, vinblastine, its alternative metabolic pathways are unclear.

Results

Biotransformation of 1 by suspension-cultured cells of Catharanthus roseus gave a new oxidative-cleavage product (2). The structure of 2 was determined as 3-hydroxy-4-imino-catharanthine by spectroscopic methods. Maximum conversion (9.75 %) of 2 was observed after 120 h adding 6 mg of 1/100 ml to 12-day-old suspension-cultured cells of C. roseus. Furthermore, qRT-PCR experiment was performed to reveal the effect of 1 on the expression of the genes in the biosynthetic pathway of TIA 1 up-regulated the transcript level of D4H whilst down-regulating the transcript levels of G10H, LAMT, GES, and IRS.

Conclusion

A new metabolite of catharanthine, 3-hydroxy-4-imino-catharanthine, is reported.

Keywords

Biotransformation Catharanthine Catharanthus roseus 3-Hydroxy-4-imino- catharanthine qRT-PCR Suspension-cultured cells 
This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

This research was financially supported by National Natural Sciences Foundation of China (No. 81073004, 81102771 and 81274045), Pearl River Scientific and Technological New Star Program of Guangzhou (No. 2014J2200004), the Natural Science Foundation of Guangdong Province (No. 2014A030313385) and Science and Technology Specific Project of Guangzhou (No.201300000138).

Supporting information

Supplementary Table 1—Primers used in this paper (see also Zhou et al. 2015).

Supplementary material

10529_2015_1930_MOESM1_ESM.docx (12 kb)
Supplementary material 1 (DOCX 12 kb)

References

  1. Choi JW, Cho GH, Byun SY, Kim DI (2001) Integrated bioprocessing for plant cell cultures. Adv Biochem Eng Biotechnol 72:63–102PubMedGoogle Scholar
  2. Costa MMR, Hilliou F, Duarte P, Pereira LG, Almeida I, Leech M, Memelink J, Barcelo AR, Scottomayor M (2008) Molecular cloning and characterization of a vacuolar class III peroxidase involved in the metabolism of anticancer alkaloids in Catharanthus roseus. Plant Physiol 146:403–417PubMedCentralCrossRefPubMedGoogle Scholar
  3. Furuya T, Sakamoto K, Lida K, Asada Y, Yoshikawa T, Sakai SI, Aimi N (1992) Biotransformation of tabersonine in cell suspension cultures of Catharanthus roseus. Phytochemistry 31:3065–3068CrossRefPubMedGoogle Scholar
  4. Giri A, Dhingra V, Giri CC, Singh A, Ward OP, Narasu ML (2001) Biotransformation using plant cells, organ cultures and enzyme system: current trends and future prospects. Biotechnol Adv 19:175–199CrossRefPubMedGoogle Scholar
  5. Hamada H, Nakazawa K (1991) Biotransformation of vinblastine to vincristine by cell suspension cultures of Catharanthus roseus. Biotechnol Lett 13:805–806CrossRefGoogle Scholar
  6. Lewinsohn E, Gijzen M (2009) Phytochemical diversity: the sounds of silent metabolism. Plant Sci 176:161–169CrossRefGoogle Scholar
  7. Liu JW, Zhu JH, Tang L, Wen W, Lv SS, Yu RM (2013) Enhancement of vindoline and vinblastine production in suspension-cultured cells of Catharanthus roseus by artemisinic acid elicitation. World J Micro Biotechnol 30:175–180CrossRefGoogle Scholar
  8. Noble RL (1990) The discovery of the vinca alkaloids-chemotherapeutic agents against cancer. Biochem Cell Biol 68:1344–1351CrossRefPubMedGoogle Scholar
  9. Patel S, Gaur R, Verma P, Bhakuni RS, Mathur A (2010) Biotransformation of artemisinin using cell suspension cultures of Catharanthus roseus (L.) G. Don and Lavandula officinalis L. Biotechnol Lett 32:1167–1171CrossRefPubMedGoogle Scholar
  10. Shimoda K, Yamane SY, Hirakawa H, Ohta S, Hirata T (2002) Biotransformation of phenolic compounds by the cultured cells of Catharanthus roseus. J Mol Catal B 16:275–281CrossRefGoogle Scholar
  11. Vázquez-Flota F, De Luca V, Carrillo-Pech M, Canto-Flick A, de Lourdes Miranda-Ham M (2002) Vindoline biosynthesis is transcriptionally blocked in Catharanthus roseus cell suspension cultures. Mol Biotechnol 22:1–8CrossRefPubMedGoogle Scholar
  12. Xue BL, Zhou LB, Liu JW, Yu RM (2012) Biotransformation of hydroxycoumarin derivatives by cultured suspension cells of Catharanthus roseus. Pharmazie 67:467–471PubMedGoogle Scholar
  13. Zhang ZJ, Yang J, He J, Wu XD, Shao LD, Li Y, Huang SX, Li RT, Zhao QS (2014) Vincamajorines A and B, monoterpenoid indole alkaloids with new carbon skeletons from Vinca major. Tetrahedron Lett 55:6490–6494CrossRefGoogle Scholar
  14. Zhou PF, Yang JZ, Zhu JH, He SJ, Zhang WJ, Yu RM, Zi JC, Song LY, Huang XS (2015) Effects of & #x03B2;-cyclodextrin and methyl jasmonate on the production of vindoline, catharanthine, and ajmalicine in Catharanthus roseus cambial meristematic cell cultures. Appl Microbiol Biotechnol. doi: 10.1007/s0025301566519 PubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Biotechnological Institute of Chinese Materia Medica, College of PharmacyJinan UniversityGuangzhouChina
  2. 2.Department of Natural Products Chemistry, College of PharmacyJinan UniversityGuangzhouChina

Personalised recommendations