Application of metabolic engineering to enhance the content of alkaloids in medicinal plants

Vásquez, Soledad Mora; Abascal, Guillermo Gael Wells; Leal, Claudia Espinosa; Cardineau, Guy A.; García‐Lara, Silverio

doi:10.1016/j.mec.2022.e00194

Cited by 35 publications

(17 citation statements)

References 106 publications

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“…The metabolic engineering of high value natural products in the native producer plants is often challenging, due to demanding propagation conditions, low gene transformation efficiencies, complex genetic regulation, and cross-talk between the engineered and native biosynthetic pathways. , As an alternative strategy, biosynthetic pathways of high-value plant natural products, such as benzylisoquinoline and tropane alkaloids or diterpenes such as taxol precursors, have been reconstituted in microbial heterologous hosts . Recently, the biosynthesis of the vinblastine precursors vindoline and catharanthine has been reconstituted in Saccharomyces cerevisiae to produce microgram per liter titers after extensive optimization .…”

Section: Introductionmentioning

confidence: 99%

Engineering the Biosynthesis of Late-Stage Vinblastine Precursors Precondylocarpine Acetate, Catharanthine, Tabersonine in Nicotiana benthamiana

et al. 2022

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Vinblastine is a chemotherapy agent produced by the plant Catharanthus roseus in small quantities. Currently, vinblastine is sourced by isolation or semisynthesis. Nicotiana benthamiana is a plant heterologous host that can be used for reconstitution of biosynthetic pathways as an alternative natural product sourcing strategy. Recently, the biosynthesis of the latestage vinblastine precursors precondylocarpine acetate, catharanthine, and tabersonine have been fully elucidated. However, the large number of enzymes involved in the pathway and the unstable nature of intermediates make the reconstitution of late-stage vinblastine precursor biosynthesis challenging. We used the N. benthamiana chassis and a state-of-art modular vector assembly to optimize the six biosynthetic steps leading to production of precondylocarpine acetate from the central intermediate strictosidine (∼2.7 mg per 1 g frozen tissue). After selecting the optimal regulatory element combination, we constructed four transcriptional unit assemblies and tested their efficiency. Finally, we successfully reconstituted the biosynthetic steps leading to production of catharanthine and tabersonine.

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Section: Introductionmentioning

confidence: 99%

Engineering the Biosynthesis of Late-Stage Vinblastine Precursors Precondylocarpine Acetate, Catharanthine, Tabersonine in Nicotiana benthamiana

et al. 2022

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“…To date, agroinfiltration has been proven to be effective for metabolic engineering of representative secondary metabolites such as terpenoid (Reed and Osbourn, 2018 ; Mani et al, 2021 ), alkaloid (Li et al, 2019 ; Mora-Vasquez et al, 2022 ) carotenoid (Rodriguez-Concepcion and Daros, 2022 ), anthocyanin (Fresquet-Corrales et al, 2017 ) as well as minor secondary metabolites (van Herpen et al, 2010 ; Pan et al, 2021 ), most of which were achieved in N. benthamiana. This plant species shares typical cellular compartmentalization, cofactor, and coenzymes with other plants, enabling it to introduce new synthetic pathways without extensively optimizing the system.…”

Section: Discussionmentioning

confidence: 99%

In planta Female Flower Agroinfiltration Alters the Cannabinoid Composition in Industrial Hemp (Cannabis sativa L.)

et al. 2022

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Industrial hemp is a diploid (2n = 20), dioecious plant, and an essential source of various phytochemical productions. More than 540 phytochemicals have been described, some of which proved helpful in the remedial treatment of human diseases. Therefore, further study of hemp phytochemicals in medicine is highly anticipated. Previously, we developed the vacuum agroinfiltration method, which allows the transient gene expression in hemp tissues including female flowers, where cannabinoids are produced and accumulated. In this study, we attempted to alter the composition of total CBD and THC. The RT-PCR and sanger sequence identified eleven copies of the CBDAS gene, two copies of the THCAS gene, and one CBCAS gene. Binary vectors were constructed to overexpress the CBDAS gene and silence the THCAS gene via RNA interference. The Transcript level of the CBDAS gene was increased by more than 10 times than the plants used as a control, which led to a 54% higher total CBD content. The silencing of the THCAS gene led to downregulation of the THCAS gene, with an 80% reduction in transcript levels, and total THC content was reduced to 43% compared with mock plant. These results suggest that hemp vacuum infiltration is highly effective for metabolic engineering of cannabinoids in hemp.

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“…The main objective of this strategy is to prompt cellular activity through the manipulation of cell functions using recombinant DNA technology. So far, several strategies, such as the introduction of genes isolated from the same species or different organisms, promoters enhancing target gene expression (constitutive expression of targeted genes using 35S promoter, for example), or disruptive expression of targeted gene or genes (antisens, RNA interference, or CRISPR/Cas9 technologies), have been used to achieve this purpose [ 144 ]. The most common example of genetic manipulation is the use of Agrobacterium tumefasciens -mediated genetic transformation, which can allow for the introduction of the desired gene.…”

Section: Main Biotechnological Approaches To Increasing the Productio...mentioning

confidence: 99%

Biotechnological Approaches to Producing Natural Antioxidants: Anti-Ageing and Skin Longevity Prospects

Bouzroud

Maaiden

Sobeh

et al. 2023

IJMS

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Plants are the main source of bioactive compounds that can be used for the formulation of cosmetic products. Plant extracts have numerous proven health benefits, among which are anti-ageing and skin-care properties. However, with the increased demand for plant-derived cosmetic products, there is a crucial prerequisite for establishing alternative approaches to conventional methods to ensure sufficient biomass for sustainable production. Plant tissue culture techniques, such as in vitro root cultures, micropropagation, or callogenesis, offer the possibility to produce considerable amounts of bioactive compounds independent of external factors that may influence their production. This production can also be significantly increased with the implementation of other biotechnological approaches such as elicitation, metabolic engineering, precursor and/or nutrient feeding, immobilization, and permeabilization. This work aimed to evaluate the potential of biotechnological tools for producing bioactive compounds, with a focus on bioactive compounds with anti-ageing properties, which can be used for the development of green-label cosmeceutical products. In addition, some examples demonstrating the use of plant tissue culture techniques to produce high-value bioactive ingredients for cosmeceutical applications are also addressed, showing the importance of these tools and approaches for the sustainable production of plant-derived cosmetic products.

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Application of metabolic engineering to enhance the content of alkaloids in medicinal plants

Cited by 35 publications

References 106 publications

Engineering the Biosynthesis of Late-Stage Vinblastine Precursors Precondylocarpine Acetate, Catharanthine, Tabersonine in Nicotiana benthamiana

Engineering the Biosynthesis of Late-Stage Vinblastine Precursors Precondylocarpine Acetate, Catharanthine, Tabersonine in Nicotiana benthamiana

In planta Female Flower Agroinfiltration Alters the Cannabinoid Composition in Industrial Hemp (Cannabis sativa L.)

Biotechnological Approaches to Producing Natural Antioxidants: Anti-Ageing and Skin Longevity Prospects

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