Plant cell and organ cultures have emerged as potential sources of secondary metabolites, which are used as pharmaceuticals, agrochemicals, flavors, fragrances, coloring agents, biopesticides, and food additives. In recent years, various strategies have been developed to assess biomass accumulation and synthesis of secondary compounds in cultures. Biomass accumulation and metabolite biosynthesis are two-stage events, and the parameters that control the growth and multiplication of cultured cells/organs and biomass accumulation are controlled in the first stage. Parameters that assist with the biosynthesis of metabolites are controlled in the second stage. The selection of high-producing cells or organ clones; optimization of medium parameters such as suitable medium, salt, sugar, nitrogen, phosphate, and plant growth regulator levels; and physical factors such as temperature, illumination, light quality, medium pH, agitation, aeration, and environmental gas (e.g., oxygen, carbon dioxide, and ethylene) are controlled in the first stage of the culture process. Elicitation, replenishment of nutrient and precursor feeding, permeabilization, and immobilization strategies assist with the accumulation of metabolites and can be applied in the second stage of the culture process. By following stage-specific strategies, it is possible to produce large amounts of biomass with an increase in the accumulation of secondary compounds.

Production of secondary metabolites from cell and organ cultures: strategies and approaches for biomass improvement and metabolite accumulation

Biosynthesis and biotechnological production of ginsenosides

Medicinal plants are the most important source of life saving drugs for the majority of the world's population. The biotechnological tools are important to select, multiply and conserve the critical genotypes of medicinal plants. In-vitro regeneration holds tremendous potential for the production of high-quality plant-based medicine. 
Cryopreservation is long-term conservation method in liquid nitrogen and provides an opportunity for conservation of endangered medicinal plants. In-vitro production of secondary metabolites in plant cell suspension cultures has been reported from various medicinal plants. Bioreactors are the key step towards commercial production of secondary metabolites by plant biotechnology. Genetic transformation may be a powerful tool for enhancing the productivity of novel secondary metabolites; especially by Agrobacterium rhizogenes induced hairy roots. This article discusses the applications of biotechnology for regeneration and genetic transformation for enhancement of secondary metabolite production in-vitro from medicinal plants. Key words: Bioreactors; genetic transformation; regeneration; secondary metabolites 
Abbreviations: BA: 6-Benzylaminopurine; TDZ: 1-Phenyl-3-(1,2,3-thiadiazol-5-yl) urea; NAA: a-Naphthaleneacetic acid; IAA: Indole-3 acetic acid; 2iP: 6-(g-Dimethylallylamino) purine; 2,4-D: 2,4-Dichlorophenoxyacetic acid; GA3: Gibberellic acid Trop J Pharm Res , December 2003; 2(2): 243-253

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Role of biotechnology in medicinal plants

The development of plant tissue (including organ and cell) cultures for the production of secondary metabolites has been underway for more than three decades. Plant cell cultures with the production of high-value secondary metabolites are promising potential alternative sources for the production of pharmaceutical agents of industrial importance. Medicinal plant cell suspension cultures (MPCSC), which are characterized with the feature of fermentation with plant cell totipotency, could be a promising alternative "chemical factory". However, low productivity becomes an inevitable obstacle limiting further commercialization of MPCSC and the application to large-scale production is still limited to a few processes. This review generalizes and analyzes the recent progress of this bioproduction platform for the provision of medicinal chemicals and outlines a range of trials taken or underway to increase product yields from MPCSC. The scale-up of MPCSC, which could lead to an unlimited supply of pharmaceuticals, including strategies to overcome and solution of the associated challenges, is discussed.

Medicinal plant cell suspension cultures: pharmaceutical applications and high-yielding strategies for the desired secondary metabolites

Autophagy as a molecular target for cancer treatment.

Panax ginseng C.A. Meyer (ginseng) is a well-known medicinal plant that has been traditionally used in the oriental countries for centuries. Wild ginseng is a scarce and rare commodity. Field cultivation of the ginseng plant is a time-consuming and labor-intensive process. Ginsenosides, a group of glycosylated triterpenes, also known as saponins, are the principal bioactive constituents of ginseng. The use of cell and organ culture processes has been sought as a potential alternative for the efficient mass production of ginseng raw material. Various bioprocessing strategies have been developed to date. Cells and adventitious roots have been cultured in large-scale bioreactors and various strategies have been developed accordingly for the enhancement of biomass and ginsenoside accumulation. This review highlights the recent progress in the cultivation of ginseng cell and organ cultures for the production of ginsenosides from bioreactor cultures. In addition, the metabolism and biochemistry of ginsenoside biosynthesis, genomic and proteomic studies in ginseng, metabolic engineering, biosafety, toxicological evaluation, and efficacy assessment of ginseng raw material are also summarized and thoroughly discussed.

Ginsenosides: prospective for sustainable biotechnological production.

https://www.koreascience.or.kr:443/article/JAKO200311921597483.pdf

Adventitious Root Cultures of Panax ginseng C.V. Meyer and Ginsenoside Production through Large-Scale Bioreactor System

We examined the effects of abiotic (methyl jasmonate [MeJA] and salicylic acid [SA]) and biotic (yeast extract and chitosan) elicitors for improvement of bioactive compounds production on adventitious root cultures in Polygonum multiflorum. The application of yeast extract resulted in significantly (p ≤ 0.05) higher dry root biomass (9.98 g/L) and relative growth rate versus the control. Cultures treated with abiotic elicitors showed higher percentage of dry weight than the other samples. Low concentrations of all elicitors (50 μM MeJA and SA, and 50 mg/L yeast extract) improved secondary metabolite production except for chitosan, whose performance was worse than that of the control. HPLC analysis of various bioactive compounds revealed significantly higher elicitation efficiency for MeJA than for the other treatments, with an approximately 2-fold increase in root dry weight (22.08 mg/g DW) under 50 μM MeJA treatment versus the control (10.35 mg/g DW). We also investigated the feasibility of scaling up the production process by comparing shake flask cultures with 3- and 5-L balloon type bubble bioreactors (BTBB) using 50 μM MeJA as an elicitor. Growth and metabolite accumulation increased in BTBB compared with shake flask cultures. We detected a non-significant difference in biomass productivity between 3 and 5-L BTBB, but the efficiency of bioactive compound accumulation decreased with increasing volume. These findings will be useful for developing a pilot-scale P. multiflorum adventitious root cultivation process for high biomass and bioactive compound production to meet the demands for natural ingredients by the pharmaceutical and cosmetic industries without affecting the natural habitat of this plant.

Improvement of biosynthesis and accumulation of bioactive compounds by elicitation in adventitious root cultures of Polygonum multiflorum.

Improved production of ginsenosides in suspension cultures of ginseng by medium replenishment strategy.

Centella asiatica contains various triterpenoids, including madecassoside, asiaticoside, madecassic acid, and asiatic acid. Among them, they are mainly contained in leaf, and among them asiaticoside is known as tissue-specific compound that are mainly accumulated in the leaves. Therefore, in the present study, C. asiatica hairy root cultures were established from petiole and leaf explants using Agrobacterium rhizogenes-mediated transformation. To promote the biosynthesis of these triterpenoids, hairy root cultures were treated with precursors (squalene and pyruvic acid) and elicitors [methyl jasmonate (MeJA) and salicylic acid (SA)] at various concentrations. No significant difference was detected in the growth index of hairy root cultures between precursor feeding and elicitation, except pyruvic acid feeding, suggesting that elicitors do not affect the growth of hairy roots. Treatment with 2.5 mM squalene and 5 mM pyruvic acid enhanced the biosynthesis of target triterpenoids (57.53 and 29.13 mg g−1 DW, respectively) compared with other treatments. However, compared to squalene, MeJA showed a greater effect on the triterpene saponin content in C. asiatica. The highest quantity of triterpenoids (60.25 mg g−1 DW) was produced in hairy root cultures treated with 400 μM MeJA. These results indicate that precursor- and elicitor-treated C. asiatica hairy root cultures rapidly accumulate biomass and could be used to enhance the production of triterpenoids for industrial purposes.

Cheol-Seung Jeong

Papers

Ginsenosides: prospective for sustainable biotechnological production.

Adventitious Root Cultures of Panax ginseng C.V. Meyer and Ginsenoside Production through Large-Scale Bioreactor System

Improvement of biosynthesis and accumulation of bioactive compounds by elicitation in adventitious root cultures of Polygonum multiflorum.

Improved production of ginsenosides in suspension cultures of ginseng by medium replenishment strategy.

Enhanced biosynthesis of triterpenoids in Centella asiatica hairy root culture by precursor feeding and elicitation