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

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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Artemisinic Acid Serves as a Novel ORCA3 Inducer to Enhance Biosynthesis of Terpenoid Indole Alkaloids in Catharanthus roseus Cambial Meristematic Cells

Natural Product Communications ◽

10.1177/1934578x1601100604 ◽

2016 ◽

Vol 11 (6) ◽

pp. 1934578X1601100

Author(s):

Mingxuan Wang ◽

Jiachen Zi ◽

Jianhua Zhu ◽

Shan Chen ◽

Pu Wang ◽

...

Keyword(s):

Catharanthus Roseus ◽

Indole Alkaloids ◽

Fold Increase ◽

Tryptophan Decarboxylase ◽

Terpenoid Indole Alkaloids ◽

Strictosidine Synthase ◽

Octadecanoid Pathway ◽

Artemisinic Acid ◽

Meristematic Cells ◽

Ap2 Domain

To investigate the effect of artemisinic acid (AA) on improving the production of terpenoid indole alkaloids (TIAs) of Catharanthus roseus cambial meristematic cells (CMCs), feeding AA to C. roseus CMCs caused 2.35-fold and 2.51-fold increases in the production of vindoline and catharanthine, respectively, compared with those of the untreated CMCs. qRT-PCR experiments showed that AA resulted in a 1.36-8.52 fold increase in the transcript levels of several related genes, including octadecanoid-derivative responsive Catharanthus AP2-domain protein 3 (ORCA3), tryptophan decarboxylase (TDC), strictosidine synthase (STR) and desacetoxyvindoline 4-hydroxylase (D4H). However, no effect was observed on the concentration of either jasmonic acid (JA), or the octadecanoid-pathway inhibitors block TIA accumulation caused by AA. The results indicated that AA might serve as a novel ORCA3 inducer to manipulate biosynthesis of TIAs in C. roseus CMCs via an unknown mechanism.

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Transgenic studies for modulating terpenoid indole alkaloids pathway in Catharanthus roseus: present status and future options

Phytochemistry Reviews ◽

10.1007/s11101-015-9447-8 ◽

2015 ◽

Vol 16 (1) ◽

pp. 19-54 ◽

Cited By ~ 9

Author(s):

Priyanka Verma ◽

Ajay Kumar Mathur ◽

Shamshad Ahmad Khan ◽

Neha Verma ◽

Abhishek Sharma

Keyword(s):

Catharanthus Roseus ◽

Present Status ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids

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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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Effect of abiotic elicitation and pathway precursors feeding over terpenoid indole alkaloids production in multiple shoot and callus cultures of Catharanthus roseus

Biologia ◽

10.2478/s11756-019-00202-5 ◽

2019 ◽

Vol 74 (5) ◽

pp. 543-553 ◽

Cited By ~ 6

Author(s):

Abhishek Sharma ◽

Ajay Kumar Mathur ◽

Jawahar Ganpathy ◽

Bhrugesh Joshi ◽

Prittesh Patel

Keyword(s):

Catharanthus Roseus ◽

Indole Alkaloids ◽

Callus Cultures ◽

Multiple Shoot ◽

Terpenoid Indole Alkaloids

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Terpenoid indole alkaloid biosynthesis in Catharanthus roseus: effects and prospects of environmental factors in metabolic engineering

Biotechnology Letters ◽

10.1007/s10529-021-03179-x ◽

2021 ◽

Vol 43 (11) ◽

pp. 2085-2103

Author(s):

Yongliang Liu ◽

Barunava Patra ◽

Sanjay Kumar Singh ◽

Priyanka Paul ◽

Yan Zhou ◽

...

Keyword(s):

Gene Expression ◽

Metabolic Engineering ◽

Environmental Factors ◽

Catharanthus Roseus ◽

Abiotic Factors ◽

Indole Alkaloids ◽

Indole Alkaloid ◽

Terpenoid Indole Alkaloids ◽

Madagascar Periwinkle ◽

Specialized Metabolites

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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Metabolomics Analysis Reveals that Ethylene and Methyl Jasmonate Regulate Different Branch Pathways to Promote the Accumulation of Terpenoid Indole Alkaloids in Catharanthus roseus

Journal of Natural Products ◽

10.1021/acs.jnatprod.7b00782 ◽

2018 ◽

Vol 81 (2) ◽

pp. 335-342 ◽

Cited By ~ 7

Author(s):

Xiao-Ning Zhang ◽

Jia Liu ◽

Yang Liu ◽

Yu Wang ◽

Ann Abozeid ◽

...

Keyword(s):

Methyl Jasmonate ◽

Catharanthus Roseus ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids ◽

Metabolomics Analysis

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CrMYC1 transcription factor overexpression promotes the production of low abundance terpenoid indole alkaloids in Catharanthus roseus

Plant Omics ◽

10.21475/poj.11.01.18.pne1020 ◽

2018 ◽

Vol 11 (01) ◽

pp. 30-36 ◽

Cited By ~ 2

Author(s):

Sima Sazegari ◽

◽

Ali Niazi ◽

Farajollah Shahriari-Ahmadi ◽

Nasrin Moshtaghi ◽

...

Keyword(s):

Transcription Factor ◽

Catharanthus Roseus ◽

Indole Alkaloids ◽

Terpenoid Indole Alkaloids

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Simultaneous Quantification of Some Pharmaceutical Catharanthus roseus Leaf and Root Terpenoid Indole Alkaloids and Their Precursors in Single Runs by Reversed-Phase Liquid Chromatography

Journal of AOAC International ◽

10.1093/jaoac/87.6.1287 ◽

2004 ◽

Vol 87 (6) ◽

pp. 1287-1296 ◽

Cited By ~ 8

Author(s):

Singh Digvijay ◽

Pandey-Rai Shashi ◽

Srivastava Suchi ◽

Rai Sanjay Kumar ◽

Mishra Raghavendra ◽

...

Keyword(s):

Catharanthus Roseus ◽

Indole Alkaloids ◽

Reversed Phase ◽

Rapid Screening ◽

Array Detector ◽

Terpenoid Indole Alkaloids ◽

Reaction Products ◽

Photodiode Array Detection ◽

Photodiode Array ◽

Phase Liquid

Abstract A new, rapid, sensitive, and reproducible reversed-phase liquid chromatographic (LC) method with photodiode array detection is described. It allows, in a single run of 30 min, simultaneous separation of 6 pharmaceutically and biologically important Catharanthus roseus leaf and root terpenoid indole alkaloids (TIAs) and 3 of their precursors: TIA precursors tryptophan, tryptamine, and loganine; and TIAs serpentine, catharanthine, ajmalicine, vincristine, vinblastine, and vindoline. The method involves the use of a Phenomenex Luna 5 μm, C18 column (250 mm × 4.6 mm id) and a linear binary gradient mobile phase profile. Detection is performed at 220 and 254 nm, which provided good absorptivity for all of the roseus compounds listed above and gave a minimum detection limit of 0.02 μg/mL. The extraction efficiency, peak purity, and homogeneity parameters of the profiles could be validated using a photodiode array detector. The method was successfully used to quantify major components of leaf and root extracts of C. roseus accessions. The new method thus provides a reliable tool for rapid screening of C. roseus samples in large numbers, which is needed in breeding/genetic engineering and genetic mapping experiments and for monitoring the reaction products, in the in vitro/in vivo conversions of precursors into products, and vice versa.

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