Production and metabolic engineering of terpenoid indole alkaloids in cell cultures of the medicinal plant Catharanthus roseus (L.) G. Don (Madagascar periwinkle)

Abstract Plants synthesize a vast array of specialized metabolites that primarily contribute to their defense and survival under adverse conditions. Many of the specialized metabolites have therapeutic values as drugs. Biosynthesis of specialized metabolites is affected by environmental factors including light, temperature, drought, salinity, and nutrients, as well as pathogens and insects. These environmental factors trigger a myriad of changes in gene expression at the transcriptional and posttranscriptional levels. The dynamic changes in gene expression are mediated by several regulatory proteins that perceive and transduce the signals, leading to up- or down-regulation of the metabolic pathways. Exploring the environmental effects and related signal cascades is a strategy in metabolic engineering to produce valuable specialized metabolites. However, mechanistic studies on environmental factors affecting specialized metabolism are limited. The medicinal plant Catharanthus roseus (Madagascar periwinkle) is an important source of bioactive terpenoid indole alkaloids (TIAs), including the anticancer therapeutics vinblastine and vincristine. The emerging picture shows that various environmental factors significantly alter TIA accumulation by affecting the expression of regulatory and enzyme-encoding genes in the pathway. Compared to our understanding of the TIA pathway in response to the phytohormone jasmonate, the impacts of environmental factors on TIA biosynthesis are insufficiently studied and discussed. This review thus focuses on these aspects and discusses possible strategies for metabolic engineering of TIA biosynthesis. Purpose of work Catharanthus roseus is a rich source of bioactive terpenoid indole alkaloids (TIAs). The objective of this work is to present a comprehensive account of the influence of various biotic and abiotic factors on TIA biosynthesis and to discuss possible strategies to enhance TIA production through metabolic engineering.

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Bioproduction of Terpenoid Indole Alkaloids from Catharanthus roseus Cell Cultures

Natural Products ◽

10.1007/978-3-642-22144-6_4 ◽

2013 ◽

pp. 85-117 ◽

Cited By ~ 3

Author(s):

Lorena Almagro ◽

Mariana Sottomayor ◽

Maria Angeles Pedreño

Keyword(s):

Cell Cultures ◽

Catharanthus Roseus ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids

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Peroxidase and the biosynthesis of terpenoid indole alkaloids in the medicinal plant Catharanthus roseus (L.) G. Don

Phytochemistry Reviews ◽

10.1023/b:phyt.0000047807.66887.09 ◽

2004 ◽

Vol 3 (1-2) ◽

pp. 159-171 ◽

Cited By ~ 40

Author(s):

M. Sottomayor ◽

I. Lopes Cardoso ◽

L.G. Pereira ◽

A. Ros Barceló

Keyword(s):

Medicinal Plant ◽

Catharanthus Roseus ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids

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Perspectives of the Metabolic Engineering of Terpenoid Indole Alkaloids in Catharanthus roseus Hairy Roots

Biotechnology of Hairy Root Systems - Advances in Biochemical Engineering/Biotechnology ◽

10.1007/10_2013_182 ◽

2013 ◽

pp. 23-54 ◽

Cited By ~ 9

Author(s):

Le Zhao ◽

Guy W. Sander ◽

Jacqueline V. Shanks

Keyword(s):

Metabolic Engineering ◽

Hairy Roots ◽

Catharanthus Roseus ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids

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Ornamental Exterior versus Therapeutic Interior of Madagascar Periwinkle (Catharanthus roseus): The Two Faces of a Versatile Herb

The Scientific World JOURNAL ◽

10.1155/2015/982412 ◽

2015 ◽

Vol 2015 ◽

pp. 1-19 ◽

Cited By ~ 18

Author(s):

Naghmeh Nejat ◽

Alireza Valdiani ◽

David Cahill ◽

Yee-How Tan ◽

Mahmood Maziah ◽

...

Keyword(s):

Catharanthus Roseus ◽

Floral Morphology ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids ◽

Madagascar Periwinkle ◽

Aesthetic Value ◽

Vernacular Names ◽

Agronomic Practices ◽

Traditional Remedy ◽

Per Se

Catharanthus roseus(L.) known as Madagascar periwinkle (MP) is a legendary medicinal plant mostly because of possessing two invaluable antitumor terpenoid indole alkaloids (TIAs), vincristine and vinblastine. The plant has also high aesthetic value as an evergreen ornamental that yields prolific blooms of splendid colors. The plant possesses yet another unique characteristic as an amiable experimental host for the maintenance of the smallest bacteria found on earth, the phytoplasmas and spiroplasmas, and serves as a model for their study. Botanical information with respect to synonyms, vernacular names, cultivars, floral morphology, and reproduction adds to understanding of the plant while the geography and ecology of periwinkle illustrate the organism’s ubiquity. Good agronomic practices ensure generous propagation of healthy plants that serve as a source of bioactive compounds and multitudinous horticultural applications. The correlation between genetic diversity, variants, and TIA production exists. MP is afflicted with a whole range of diseases that have to be properly managed. The ethnobotanical significance of MP is exemplified by its international usage as a traditional remedy for abundant ailments and not only for cancer. TIAs are present only in micro quantities in the plant and are highly poisonousper serendering a challenge for researchers to increase yield and reduce toxicity.

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Production of Secondary Metabolites in Cell Cultures of Some Terpenoid-Indole Alkaloids Producing Plants

Plant Vacuoles ◽

10.1007/978-1-4684-5341-6_62 ◽

1987 ◽

pp. 485-494

Author(s):

R. Verpoorte ◽

R. Wijnsma ◽

P. A. A. Harkes ◽

H. J. G. ten Hoopen ◽

J. J. Meijer ◽

...

Keyword(s):

Secondary Metabolites ◽

Cell Cultures ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids

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Effect of Aspergillus flavus Fungal Elicitor on the Production of Terpenoid Indole Alkaloids in Catharanthus roseus Cambial Meristematic Cells

Molecules ◽

10.3390/molecules23123276 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3276

Author(s):

Chuxin Liang ◽

Chang Chen ◽

Pengfei Zhou ◽

Lv Xu ◽

Jianhua Zhu ◽

...

Keyword(s):

Suspension Culture ◽

Aspergillus Flavus ◽

Catharanthus Roseus ◽

Indole Alkaloids ◽

Fungal Elicitor ◽

Control Group ◽

Terpenoid Indole Alkaloids ◽

Meristematic Cells ◽

Qrt Pcr ◽

Induction Process

This study reported the inducing effect of Aspergillus flavus fungal elicitor on biosynthesis of terpenoid indole alkaloids (TIAs) in Catharanthus roseus cambial meristematic cells (CMCs) and its inducing mechanism. According to the results determined by HPLC and HPLC-MS/MS, the optimal condition of the A. flavus elicitor was as follows: after suspension culture of C. roseus CMCs for 6 day, 25 mg/L A. flavus mycelium elicitor were added, and the CMC suspensions were further cultured for another 48 h. In this condition, the contents of vindoline, catharanthine, and ajmaline were 1.45-, 3.29-, and 2.14-times as high as those of the control group, respectively. Transcriptome analysis showed that D4H, G10H, GES, IRS, LAMT, SGD, STR, TDC, and ORCA3 were involved in the regulation of this induction process. The results of qRT-PCR indicated that the increasing accumulations of vindoline, catharanthine, and ajmaline in C. roseus CMCs were correlated with the increasing expression of the above genes. Therefore, A. flavus fungal elicitor could enhance the TIA production of C. roseus CMCs, which might be used as an alternative biotechnological resource for obtaining bioactive alkaloids.

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