The Role of Agricultural Biotechnology and Genetic Engineering in the Improvement of Medicinal Plants in Afghanistan

Rabia Ayoubi; Aliyu Isa; Aqa Mohammad Zhakfar

doi:10.62810/jnsr.v2iSpecial.Issue.98

Authors

Rabia Ayoubi Department of Pharmacognosy, Faculty of Pharmacy, Kabul University
Aliyu Isa Department of Biotechnology, Faculty of Life Sciences, University of Maiduguri, Borno State – Nigeria
Aqa Mohammad Zhakfar Department of Pharmaceutics, Faculty of Pharmacy, Kabul University, Afghanistan

DOI:

https://doi.org/10.62810/jnsr.v2iSpecial.Issue.98

Keywords:

Agricultural biotechnology, Genetic engineering, Aromatic plants, Alkaloids, Flavonoids, Medicinal plants

Abstract

Most pharmaceutical products are derived from plants, making plants an essential source for developing and discovering novel therapeutic compounds. The phytochemical components of medicinal plants (MPs), particularly the secondary metabolites (SMs), are linked to the pharmacological effects of MPs. The widespread interest in phytotherapy, consumer preference to use natural resources, the continuous exploitation of natural resources, the economic importance of MPs in the self-sufficiency of developing countries like Afghanistan, difficulties associated with the traditional breeding methods of MPs, and resulting insufficient plant yield have made wild MPs resources unable to meet the current requirements and led researchers to search for alternative solutions. The application of genetic engineering (GE) techniques and biotechnological tools, including combinatorial biosynthesis, CRISPR/Cas9-based systems, and genetically encoded biosensors to select, multiply, improve the bio-production, biodiversity preservation; conservation of the elite and rare genotypes of important MP species in extinction is considered a possible solution. Afghanistan is one of the main exporters of MPs due to its rich flora. Even though it’s uncommon in the country to apply modern biotechnology and GE procedures to improve MPs, they may still be considered promising methods. This paper reviewed the recent successes and developments in the previously/at present use of various biotechnological and GE approaches for the improvement of MPs in Afghanistan and also to identify the main challenges the country’s plant breeders and/or scientists may face during the use of these approaches to improve MPs shortly.

Downloads

Download data is not yet available.

References

Agriculture and forestry. (2023). (Encyclopædia Britannica, inc.) Retrieved 12 9, 2023, from Encyclopædia Britannica: https://www.britannica.com/place/Afghanistan/Agriculture-and-forestry

Ahmad, B., Raina, A., & Khan, S. (2019). Secondary metabolite production in medicinal plants using tissue cultures. Medically Important Plant Biomes; source of secondary metabolites, 15, 133- 52.

Ahmad, I., Hussain, T., Ashraf, I., Nafees, M., Maryam, R. M., & Iqbal, M. (2013). Lethal effects of secondary metabolites on plant tissue culture. Am. Eurasian J. Agric. Environ. Sci, 13, 539–547.

Ahmad, S., Garg, M., Tamboli, E. T., Abdin, M. Z., & Ansari , S. H. (2013). In vitro production of alkaloids: Factors, approaches, challenges and prospects. Pharmacognosy Reviews, 7(13), 27- 33.

Al-Jibouri, A. M., Abed, A. S., Ali, A.-J. A., & Majeed, D. M. (2016). Improvement of Phenols Production by Amino Acids in Callus Cultures of Verbascum thapsus L. American Journal of Plant Sciences, 7, 84-91.

Amer, A. (2018). BIOTECHNOLOGY APPROACHES FOR IN VITRO PRODUCTION OF FLAVONOIDS. J Microbiol Biotech Food Sci, 7(5), 457-468.

Amiri, M. S., Joharchi, M. R., Nadaf, M., & Nasseh, Y. (2020). Ethnobotanical knowledge of Astragalus spp.: The world’s larges genus of vascular plants. Avicenna J Phytomed, 10(2), 128-142.

Aziz, Z. A., Ahmad, A., Setapar, S. H., Karakucuk, A., Azim, M. M., Lokhat, D., & Ashraf, G. M. (2018). Essentialoils: Extractiontechniques, pharmaceutical and therapeutic potential-a review. Curr. Drug Metab, 19, 1100–1110.

Babury, M. O. (2019). Sustainable Resource Management of Medicinal and Aromatic Plants of Afghanistan.

Baust, J. G., Gao, D., & Baust, J. M. (2009). Cryopreservation. Organogenesis., 5(3), 90–96.

Benedito, V. A., & Modolo, L. V. (2014). Introduction to metabolic genetic engineering for the production of valuable secondary metabolites in in vivo and in vitro plant systems. Recent Pat Biotechnol, 8(1), 61-75. doi:10.2174/1872208307666131218125801

Bourgaud, F., Gravot, A., Milesi, S., & Gontier, E. (2001). Production of plant secondary metabolites: a historical perspective. Plant Science, 161(5), 839- 51. doi:https://doi.org/10.1016/S0168-9452(01)00490-3

Breckle, S. W., Hedge, I. C., & Rafiqpoor, M. D. (2013). Vascular Plants of Afghanistan – an Augmented Checklist. Bonn: Scientia Bonnensis.

Campêlo, M. C., Medeiros, J. M., & Silva, J. B. (2019). Natural products in food preservation. Int. Food Res. J, 26, 130.

Canel, C., Lopes-Cardoso, M. L., Whitmer, S., Van der Fits, L., Pasquali, G., Van der Heijden, R., . . . Verpoorte, R. (1998). Effects of over-expression of strictosidine synthase and tryptophan decarboxylase on alkaloid production by cell cultures of Catharanthus roseus. Planta, 205, 414–419.

Canter, P. H., Thomas, H., & Ernst, E. (2005). Bringing medicinal plants into cultivation: Opportunities and challenges for biotechnology. Trends in Biotechnology, 23(4), 180-5.

Carvalho, Y. G., Vitorino, L. C., de Souza, U. J., & Bessa, L. A. (2019). Recent Trends in Research on the Genetic Diversity of Plants: Implications for Conservation. Diversity, 11(4), 62.

Chandran, H., Meena, M., Barupal, T., & Sharma, K. (2020). Plant tissue cultures as a perpetual source for production of industrially important bioactive compounds. Biotechnology Reports, 26, e00450. doi:https://doi.org/10.1016/j.btre.2020.e00450

Chen, D. H., Ye, H. C., & Li, G. F. (2000). Expression of a chimeric farnesyl diphosphate synthase gene in Artemisia annua L. transgenic plants via Agrobacterium tumefaciens-mediated transformation. Plant Sci, 155, 179–185.

Cheng, T., Zhao, G., Xian, M., & Xie, C. (2020). Improved cis-abienol production through increasing precursor supply in Escherichiacoli. Sci. Rep, 10, 16791.

Ciddi, V., Srinivasan, V., & Shuler, V. (1995). Elicitation of Taxus cell cultures for production of taxol. Biotechnol Lett, 17, 1343–6.

Croteau, R., Kutchan, T. M., & Lewis, N. G. (2000). Natural products (secondary metabolites). In B. Buchanan, W. Gruissem, & R. Jones (Eds.), Biochemistry and Molecular Biology of Plants (pp. 1250–1318). American Society of Plant Physiologists, Rockville, MD.

Cui, L., Ni, X., Ji, Q., Teng, X., Yang, Y., C.Wu, . . . Kai, G. (2015). Co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in Ophiorrhiza pumila. Sci. Rep, 5, 1- 9.

Debnath , S. C., & Goyali , J. C. (2020). In Vitro Propagation and Variation of Antioxidant Properties in Micropropagated Vaccinium Berry Plants—A Review. Molecules, 25, 788.

Dehghan , E., Hosseini , B., Naghdi , H. B., & Shahriari , F. A. (2010). Application of Conventional and New Biotechnological Approaches for Improving of Morphinane Alkaloids Production. Journal of Medicinal Plants, 9(35).

Di Gioia, D., Luziatelli, F., Negroni, A., Ficca, A. G., Fava, F., & Ruzzi, M. (2011). Metabolic engineering of Pseudomonasﬂuorescens for the production of vanillin from ferulic acid. J. Biotechnol, 156, 309–316.

Dias, M. I., Sousa, M. J., Alves, R. C., & Ferreira, I. C. (2016). Exploring plant tissue culture to improve the production of phenolic compounds: A review. Industrial Crops and Products, 82, 9-22.

Dong, Y., Duan, W., He, H., Su., P., Zhang, M., Song, G., . . . Yu, I. (2015). Enhancing taxane biosynthesis in cell suspension culture of Taxus chinensis by overexpressing the neutral/alkaline invertase gene. Process Biochem, 50, 651- 60.

Dörnenburg, H., & Knorr, D. (1995). Strategies for the improvement of secondary metabolite production in plant cell cultures. Enzyme and Microbial Technology, 17(8), 674- 84. doi:https://doi.org/10.1016/0141-0229(94)00108-4

Dudareva, N., Cseke, L., Blanc, V. M., & Pichersky, E. (1996). Evolution of floral scent in Clarkia: Novel patterns of S-linalool synthase gene expression in the C. breweri flower. Plant Cell, 8, 1137–1148.

Ebrahimi, M., & Mokhtari, A. (2017). Engineering of secondary metabolites in tissue and cell culture of medicinal plants: an alternative to produce benefecial compounds using bioreactor technologies. In S. Abdullah, H. Chai-Ling, & C. Wagstaff (Eds.), Crop Improvement (pp. 137- 67). Springer, Cham. doi:https://doi.org/10.1007/978-3-319-65079-1_7

ECLRC. (2010). A STUDY ON APPLICABILITY OF BIOTECHNOLOGY TO DEVELOPMENT IN THE CARIBBEAN: OPPORTUNITIES AND RISKS . UN.

Edesi, J., Tolonen, J., Ruotsalainen, A. L., Aspi, J., & Häggman, H. M. (2020). Cryopreservation enables long-term conservation of critically endangered species Rubus humulifolius. Biodiversity and Conservation, 29(1), 303–314 .

Facchini, P. J., Huber-Allanach, K. L., & Tari, L. W. (2000). Plant aromatic L-amino acid decarboxylases: evolution, biochemistry, regulation, and metabolic engineering applications. Phytochemistry, 54, 121–138.

Farnsworth, N. R. (1990). The role of ethnopharmacology in drug development. Ciba Foundation Symposium, 154, 2–11.

Farnsworth, N. R., & Morris, R. W. (1976). Higher plants – the sleeping giant of drug development. Am. J. Pharm. Sci. Support Public Health, 148(2), 46–52.

Farnsworth, N. R., Akerele, O., Bingel, A. S., Soejarto, D. D., & Guo, Z. (1985). Medicinal plants in therapy. Bull. World Health Organ, 63, 965–981.

Fierascu, R. C., Fierascu, I., Ortan, A., Georgiev, M. I., & Sieniawska, E. (2020). Innovative approaches for recovery of phytoconstituents from medicinal/aromatic plants and biotechnological production. Molecules, 25, 309.

Figlan, S., & Makunga, N. P. (2017). Genetic transformation of the medicinal plant Salviaruncinata L. f. usingAgrobacteriumrhizogenes. S.Afr. J. Bot, 112, 193–202.

Freitag, H., Hedge, I., Rafiqpoor, M. D., & Breckle , S. W. (2010). Flora and vegetation of Afghanistan. In S. W. Breckle, & M. D. Rafiqpoor (Eds.), Field Guide Afghanistan –Flora and Vegetation (pp. 79-115)). Bonn: Scientia Bonnensis.

Fumagali, E., Gonçalves, R. A., Machado, M. d., Vidoti, G. J., & Oliveira, A. J. (2008). Production of plant secondary metabolites in plant cell and tissue culture: the example of Tabernaemontana and Aspidosperma genera. Revista Brasileira de Farmacognosia, 18(4), 627- 41. doi:https://doi.org/10.1590/S0102-695X2008000400022

Ghasemi, M., Mirjalili, M. H., & Hadian, J. (2014). Chemical proﬁles of the essential oil of wild and in vitro regenerated Zataria multiﬂora Boiss (Lamiaceae). Bulg. Chem. Commun, 46, 362–367.

Ghimire, B., Yu, C., & Chung, I. (2017). Assessment of the phenolic profile, anti-microbial activity, and oxidative stability of transgenic Perilla frutescens L.overexpressing tocopherol methyltransferase (γ-tmt) gene. Plant Physiol. Biochem, 118, 77–87.

Giulietti, A., & Ertola, R. (1999). Biotechnological strategies for production of plants and secondary metabolites of pharmaceutical intrest. Acta Horticulturae, 502, 269-80. doi:https://doi.org/10.17660/ActaHortic.1999.502.44

Gonçalves, S., & Romano, A. (2018). Production of plant secondary metabolites by using biotechnological tools. doi:10.5772/intechopen.76414

Guo, Z. .., Tan, H., Lv, Z., Ji, O., Y.Huang, Liu, J., . . . Zhang, L. (2018). Targeted expression of Vitreoscilla hemoglobin improves the production of tropane alkaloids in Hyoscyamus niger hairy roots. Sci. Rep, 8, 1- 12.

Gutensohn, M., Nagegowda, D. A., & Dudareva, N. (2013). Involvement of compartmentalization in monoterpene and sesquiterpene biosynthesis in plants. In T. J. Bach, & M. Rohmer (Eds.), Isoprenoid Synthesis in Plants and Microorganisms: New Concepts and Experimental Approaches (pp. 155–169). New York, NY, USA: Springer.

Hahn , F. M., & Poulter , C. D. (1995). Isolation of Schizosaccharomyces pombe isopentenyl diphosphate isomerase cDNA clones by complementation and synthesis of the enzyme in Escherichia coli. J Biol Chem, 270, 11298-11303.

Hasnain, A., Naqvi, S. H., Ayesha, S. I., Khalid, F., Ellahi, M., Iqbal, S., . . . Abdelhamid, M. M. (2022). Plants in vitro propagation with its applications in food, pharmaceuticals and cosmetic industries; current scenario and future approaches. Front/ Plant Sci., 13, 1009395.

Heijden, R., Jacobs, D. I., Snoeijer, W., Hallard, D., & Verpoorte, R. (2004). The Catharanthus Alkaloids:Pharmacognosy and Biotechnology. Current Medicinal Chemistry, 11(5), 607-28. doi:10.2174/0929867043455846

Hidalgo, D., Martínez-Márquez, A., Cusidó, R., Bru-Martínez, R., Palazón, J., & Corchete, P. (2017). Silybum marianum cell cultures stably transformed with Vitis vinifera stilbene synthase accumulate t-resveratrol in the extracellular medium after elicitation with methyl jasmonate or methylated β-cyclodextrins. Eng. Life Sci., 17, 686–94.

Ho, C., Chang, S., & Lung, J. (2005). The Strategies to Increase Taxol Production by Using Taxus mairei Cells Transformed with TS and DBAT Genes. Int. J, 3, 179–85.

Holden, R., Holden, M., & Yeoman, M. (1988). The effects of fungal elicitation on secondary metabolism in cell cultures of Capsicum frutescens. In: Robins RJ, Rhodes MJC, editors. Manipulating secondary metabolism in culture. In R. Robins, & M. Rhodes (Eds.), Manipulating secondary metabolism in culture (pp. 67- 72). Cambridge England: Cambridge University PresS.

Huang , Q., Roessner , C. A., Croteau , R., & Scott , A. I. (2001). Engineering Escherichia coli for the synthesis of taxadiene, a key intermediate in the biosynthesis of taxol. Bioorg Med Chem, 9, 2237-2242.

Hulvová, H., Galuszka, P., Frébortová, J., & Frébort, I. (2013). Parasitic fungus Claviceps as a source for biotechnological production of ergot alkaloids. Biotechnol Adv, 31(1), 79- 89. doi:10.1016/j.biotechadv.2012.01.005

Hussain, M. S., Fared, S., Ansari, S., Rahman, M. A., Ahmad, I. Z., & Saeed, M. (2012). Current approaches toward production of secondary plant metabolites. J Pharm Bioallied Sci, 4(1), 10- 20. doi:10.4107406.927253/0975-

Inoue, M., & Craker, L. E. (2014). Medicinal and aromatic plants-Uses and functions. In Horticulture: PlantsforPeopleandPlaces (Vol. 2, pp. 645–669). Dordrecht, The Netherlands: Springer.

Justin, Kabera, Edmond, Semana, Ally, Mussa, . . . He. (2014). Plant secondary metabolites: biosynthesis, classification, function and pharmacological properties. Journal of Pharmacy and Pharmacology, 2, 377- 92.

Kayser , O., & Quax , W. J. (Eds.). (2007). Medicinal Plant Biotechnology. From Basic Research to Industrial Applications. Weinheim : WILEY-VCH Verlag GmbH & Co.

Khakdan, F., Shirazi, Z., & Ranjbar, M. (2022). Identiﬁcation and functional characterization of the CVOMTs and EOMTs genes promoters from Ocimum basilicum L. Plant Cell Tissue Organ Cult, 148, 387–402.

Khalil, A. (2017). Role of Biotechnology in Alkaloids Production. In Catharanthus roseus (M. Naeem, T. Aftab, & M. Khan, Trans., pp. 59- 70). Springer, Cham. doi:https://doi.org/10.1007/978-3-319-51620-2_4

Khan, M. Y., Saleh, A., Vimal, K., & Rajkumar, S. (2009). Recent advaces in medicinal plant biotechnology. Indian Journal of Biotechnology, 8(1), 9- 22.

Kirsi-Marja, & Oksman-Caldentey. (2007). Tropane and nicotine alkaloid biosynthesis-novel approaches towards biotechnological production of plant-derived pharmaceuticals. Curr Pharm Biotechnol, 8(4), 203- 10. doi:10.2174/138920107781387401

Kowalczyk, T., Wieczfinska, J., Skała, E., Śliwiński, T., & Sitarek, P. (2020). Transgenesis as a Tool for the Efficient Production of Selected Secondary Metabolites from Plant in Vitro Cultures. Plants, 9(2), 132. doi:https://doi.org/10.3390/plants9020132

Kreis, W., & Reinhard, E. (1989). The production of secondary metabolites by plant cells cultivated in bioreactors. Planta Med, 55(5), 409-16. doi:10.1055/s-2006-962054

Kuluev, B. R., Saﬁullina, M. G., Knyazev, A. V., & Chemeris, A. V. (2013). EffectofectopicexpressionofNtEXPA5geneoncellsizeandgrowth of organs of transgenic tobacco plants. Russ. J. Dev. Biol, 44, 28–34.

Kutchan , T. M., Bock , A., & Dittrich , H. (1994). Heterologous expression of the plant proteins strictosidine synthase and berberine bridge enzyme in insect cell culture. Phytochemistry, 35, 353-360.

Lim, S. S., Jung, S. H., Ji, J., Shin, K. H., & Keum, S. R. (2001). Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. J.Pharm.Pharmacol, 53(5), 653-68.

Lubbers, R. J., Dilokpimol, A., Visser, J., Mäkelä, M. R., Hildén, K. S., & de Vries, R. P. (2019). A comparison between the homocyclic aromatic metabolic pathways from plant-derived compounds by bacteria and fungi. Biotechnol. Adv, 37, 107396.

M.Cragg, G., & J.Newman, D. (2005). Plants as a source of anti-cancer agents. Journal of Ethnopharmacology, 100(1- 2), 72- 9. doi:https://doi.org/10.1016/j.jep.2005.05.011

Mahmoud, S. S., & Croteau, R. B. (2001). Metabolic engineering of essential oil yield and composition in mint by altering expression of deoxyxylulose phosphate reductoisomerase and menthofuran synthase. Proc. Natl. Acad. Sci. USA, 98, 8915–8920.

Marsafari, M., Samizadeh, H., Rabiei, B., Mehrabi, A., Koﬀas, M., & Xu, P. (2020). Biotechnological Production of Flavonoids: An Update on Plant Metabolic Engineering, Microbial Host Selection, and Genetically Encoded Biosensors. Biotechnol. J. , 1900432.

Math , S. K., Hearst , J. E., & Poulter , C. D. (1992). The crtE gene in Erwinia herbicola encodes geranylgeranyl diphosphate synthase. Proc Natl Acad Sci USA, 89, 6761-6764.

Máthé, A., Hassan, F., & Abdul Kader, A. (2015). In vitro micropropagation of medicinal and aromatic plants. In MedicinalandAromatic Plants of the World (pp. 305–336). Dordrecht, The Netherlands: Springer.

Mavel, S., Dikic, B., Palakas, S., Emond, P., Greguric, I., Gracia, A. G., . . . Katsiﬁs, A. (2006). Isoflavonoid Production by Genetically Engineered Microorganisms. Bioorg. Med. Chem, 14, 1599.

Misawa , N., Nakagawa , M., Kobayashi , K., Yamano , S., Izawa , Y., Nakamura , K., & Harashima , K. (1990). Elucidation of the Erwinia uredovora carotenoid biosynthetic pathway by functional analysis of gene products expressed in Escherichia coli. J Bacteriol, 172, 6704-6712.

Mittal, J., & Sharma, M. (2017). Enhanced production of berberine in In vitro regenerated cell of Tinospora cordifolia and its analysis through LCMS QToF. 3. Biotech , 7, 1- 12.

Miura , Y., Kondo , K., Shimada , H., Saito , T., Nakamura , K., & Misawa , N. (1998). Production of lycopene by the food yeast, Candida utilis that does not naturally synthesize carotenoid. Biotechnol Bioeng, 58, 306-308.

Mohsen Niazian. (2019). Application of genetics and biotechnology for improving medicinal plants. Planta, 249(4), 953- 973.

Mulabagal Vanisree, C. Y., Lo, S. F., Nalawade, S. M., Lin, C. Y., & Sheng, H. (2004). Studies on the production of some important secondary metabolite from medicinal plants by plant tissue cultures. Bot. Bull. Acad. Sin., 45(1), 1- 22.

Nabavi, S. M., Šamec, D., Tomczyk, M., Milella, L., Russo, D., Habtemariam, S., . . . Shirooie, S. (2020). Flavonoid biosynthetic pathways in plants: Versatile targets for metabolic engineering. Biotechnol Adv, 38, 107316.

Narayani, M., & Srivastava, S. (2017). Elicitation: a stimulation of stress in in vitro plant cell/tissue cultures for enhancement of secondary metabolite production. Phytochemistry Reviews , 16, 1227- 52.

Nartop, P. (2018). Engineering of Biomass Accumulation and Secondary Metabolite Production in Plant Cell and Tissue Cultures. In Plant Metabolites and Regulation Under Environmental Stress (pp. 169-94). doi:https://doi.org/10.1016/B978-0-12-812689-9.00009-1

Ni, X., Wen, S., Wang, X., Wang, W., Xu, H., & Kai, G. (2011). Enhancement of camptothecin production in Camptotheca acuminata hairy roots by overexpressing ORCA3 gene. J. Appl. Pharm. Sci, 1, 85- 8.

Ortiz, R. (1998). Critical role of plant biotechnology for the genetic improvement of food crops: perspectives for the next millennium. Electronic Journal of Biotechnology, 1(3), 2- 8.

Ouyang, B., Gu, X., & Holford, P. (2017). Plant genetic engineering and biotechnology: a sustainable solution for future food security and industry. Plant Growth Regul, 1- 3.

Ozyigit, I. I., Dogan, I., -Ozyigit,, A. H., Yalcin, B., Erdogan, A., Yalcin, I. E., . . . Kaya, Y. (2023). Production of secondary metabolites using tissue culture-based biotechnological applications. Front Plant Sci, 14, 1132555.

Pan, Q., Wang, C., Xiong, Z., Wang, H., Fu, X., Shen, Q., . . . Tang., K. (2019). CrERF5, an AP2/ERF transcription factor, positively regulates the biosynthesis of bisindole alkaloids and their precursors in Catharanthus roseus. Front. Plant Sci, 10, 1- 13.

Pandey, A. K., Kumar, P., Saxena, M. J., & Maurya, P. (2020). Distribution of aromatic plants in the world and their properties. In Feed Additives (pp. 89–114). MA, US: Academic Press.

Patel, D. K. (2016). Medicinal and Aromatic Plants: Role in Human Society. Med. Aromat. Plants, 5, 3.

Paul, S., El Bethel Lalthavel Hmar, J. H., & Zothantluanga, H. K. (2020). Essential oils: A review on their salient biological activities and major delivery strategies. J. Mizo Acad. Sci, 20, 54–71.

Picaud , S., Olofsson , L., Brodelius , M., & Brodelius , P. E. (2005). Expression, purification, and characterization of recombinant amorpha-4,11-diene synthase from Artemisia annua L. Arch Biochem Biophys, 436 , 215-226.

Podlech, D., & Anders, O. (1977). FLORULA DES WAKHAN (NORDOST-AFGHANISTAN). (``, Ed.) Mitteilungen der Botanischen Staatssammlung München, 13, 361--502.

Ptak, A., Morańska, E., Skrzypek, E., Warchoł, M., Spina, R., Laurain-Mattar, D., & Simlat, M. (2020). Carbohydrates stimulated Amaryllidaceae alkaloids biosynthesis in Leucojum aestivum L. plants cultured in RITA® bioreactor. Peer J, 8, e8688. doi:10.7717/peerj.8688

Rates, S. (2001). Plants as sources of drugs. Toxicon, 39, 603–613.

Raut, J. S., & Karuppayil, S. M. (2014). A status review on the medicinal properties of essential oils. Ind. Crops Prod, 62, 250–264.

Řeháček, Z. (1984). Biotechnology of ergot alkaloids. 2-(6), 166- 72.

Rehman, S. U., Faisal, R., Shinwari, Z. K., Ahmad, N., & Ahmad, I. (2017). Phytochemical Screening and Biological Activities of Trigonella incisa and Nonea edgeworthii. Pakistan Journal of Botany, 49(3), 1161-1165.

Rikhari, H., & et al. (2000). The effect of disturbance levels, forest types and associations on the regeneration of Taxus baccata: Lessons from the Central Himalayo. Curr. Sci, 79–88.

Rodney, C., Toni, M., N.Kutchan, & Lewis, G. (2000). Natural products. Biochemistry and Molecular Biology of Plants, 1253-1348.

Ruffoni, B., Pistelli, L., Bertoli, A., & Pistelli, L. (2010). Plant Cell Cultures: Bioreactors for Industrial Production. Adv Exp Med Biol, 698, 203-21. doi:10.1007/978-1-4419-7347-4_15

Saito, K. (1992). Transgenic herbicide-resistant Atropa belladonna using an Ri binary vector and inheritance to the transgenic trait. Plant Cell Rep, 21, 563–568.

Saito, K. (1994). Molecular genetics and bio–technology in medicinal plants: studies by transgenic plants. Yakugaku Zasshi, 114(1), 1–20.

Sakato, K., Tanaka, H., Mukai, N., & Misawa, M. (1974). Isolation and Identification of Camptothecin from Cells of Camptotheca acuminata Suspension Cultures. Agric. Biol. Chem, 38, 217- 8.

Salim, A. A., Chin, Y.-W., & Kinghorn, A. D. (2008). Drug discovery from plants. In K. Ramawat, & J. Merillon (Eds.), Angela A. SalimYoung-Won ChinA. Douglas Kinghorn (pp. 1- 24). Springer, Berlin, Heidelberg. doi:https://doi.org/10.1007/978-3-540-74603-4_1

Samanani , N., & Facchini , P. J. (2002). Purification and characterization of norcoclaurine synthase. The first committed enzyme in benzylisoquinoline alkaloid biosynthesis in plants. J Biol Chem, 277, 33878-33883.

Samanani , N., Liscombe , D. K., & Facchini , P. J. (2004). Molecular cloning and characterization of norcoclaurine synthase, an enzyme catalyzing the first committed step in benzylisoquinoline alkaloid biosynthesis. Plant J, 40, 302-313.

Sato, F., Hashimoto, T., Hachiya, A., Tamura, K.-i., Choi, K.-B., Morishige, T., . . . Yamada, Y. (2001). Metabolic engineering of plant alkaloid biosynthesis. PNAS, 98(1), 367–372.

Sazegari, S., Niazi, A., Shahriari-Ahmadi, F., Moshtaghi, N., & Ghasemi, Y. (2018). CrMYC1 transcription factor overexpression promotes the production of low abundance terpenoid indole alkaloids in Catharanthus roseus. Plant OMICS, 11, 30- 6.

Schäfer, H., & Wink, M. (2009). Medicinally important secondary metabolites in recombinant microorganisms or plants: Progress in alkaloid biosynthesis. Biotechnology Journal, 4(12), 1684-1703. doi:https://doi.org/10.1002/biot.200900229

Schmidt, E. (2020). Production of essential oils. In Handbook of Essential Oils (pp. 125–160). Boca Raton, FL, USA: CRC Press.

Shah, F. L., Ramzi, A. B., Baharum, S. N., Noor, N. M., Goh, H. H., Leow, T. C., . . . Sabri, S. (2019). Recent advancement of engineering microbial hosts for the biotechnological production of flavonoids. Molecular Biology Reports.

Sharma, H. C., Crouch, J. H., Sharma, K. K., Seetharama, N., & Hash, C. T. (2002). Applications of biotechnology for crop improvement: prospects and constraints. Plant Science, 163.

Sharma, S., & Shahzad, A. (2013). Bioreactors: A Rapid Approach for Secondary Metabolite Production. In M. Shahid, A. Shahzad, A. Malik, & A.Sahai (Eds.), Recent Trends in Biotechnology and Therapeutic Applications of Medicinal Plants. (pp. 25- 49). Springer, Dordrecht. doi:https://doi.org/10.1007/978-94-007-6603-7_2

Shelepova , O. V., Baranova , E. N., Tkacheva , E. V., Evdokimenkova , Y. B., Ivanovskii , A. A., Konovalova , L. N., & Gulevich , A. A. (2022). Aromatic Plants Metabolic Engineering: A Review. Agronomy, 12(3131), 2- 17.

Shimada, T., Endo, T., Rodríguez, A., Fujii, H., Goto, S., Matsuura, T., . . . et al. (2017). Ectopic accumulation of linalool confers resistance to Xanthomonascitri subsp. citri in transgenic sweet orange plants. Tree Physiol, 37, 654–664.

Sitarek, P., Kowalczyk, T., Rijo, P., Białas, A., Wielanek, M., Wysokińska, H., . . . Skała, E. (2018). Over-Expression of AtPAP1 Transcriptional Factor Enhances Phenolic Acid Production in Transgenic Roots of Leonurus sibiricus L. and Their Biological Activities. Mol. Biotechnol, 60, 74–82.

Smetanska, I. (2008). Production of Secondary Metabolites Using Plant Cell Cultures. In U. Stahl, U. Donalies, & E. Nevoigt (Eds.), Food Biotechnology (Vol. 111, pp. 187- 228). Springer, Berlin, Heidelberg. doi:https://doi.org/10.1007/10_2008_103

Srivastava, S., & Srivastava, A. K. (2013). Biotechnology and Genetic Engineering for Alkaloid Production. Natural Products, 213- 50.

Stage, T., Bergmann, T., & Kroetz, D. (2018). Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review. Clin. Pharmacokinet, 57, 7- 19.

Su, S., Liu, X., Pan, G., Hou, X., Zhang, H., & Yuan, Y. (2015). In vitro characterization of a (E)-β-farnesene synthase from Matricaria recutita L. and its up-regulation by methyl jasmonate. Gene, 571, 58–64.

Sun, B., Zhu, Z., Cao, P., Chen, H., Chen, C., Zhou, X., . . . Liu, S. (2016). Purple foliage coloration in tea (Camellia sinensis L.) arises from activation of the R2R3-MYB transcription factor CsAN1. Sci. Rep, 6, 32534.

Suprun, A., Ogneva, Z., Dubrovina, A., & Kiselev, K. (2019). Effect of spruce PjSTS1a, PjSTS2, or PjSTS3 gene overexpression on stilbene biosynthesis in callus cultures of Vitis amurensis Rupr. Biotechnol. Appl. Biochem, 1- 7.

Suzuki, H., Fukushima, E., Shimizu, Y., Seki, H., Fujisawa, Y., Ishimoto, M., . . . Muranaka, T. (2019). Lotus japonicus Triterpenoid Profile and Characterization of the CYP716A51 and LjCYP93E1 Genes Involved in Their Biosynthesis in Planta. Plant Cell Physiol, 60, 2496–2509.

Sykłowska-Baranek, K., Pilarek, M., Bonfill, M., Kafel, K., & Pietrosiuk, A. (2015). Perfluorodecalin-supported system enhances taxane production in hairy root cultures of Taxus x media var. Hicksii carrying a taxadiene synthase transgene. Plant Cell Tissue Organ Cult., 120, 1051- 9.

Thengane, S., Kulkarni, D., Shrikhande, V., Joshi, S., Sonawane, K., & Krishnamurthy, K. (2003). Influence of medium composition on callus induction and camptothecin(s) accumulation in Nothapodytes foetida. Plant Cell Tiss Org Cult, 72, 247–51.

Tomioka, K., Nishikawa, J., Moriwaki, J., & Sato, T. (2013). Effects of over-expression of strictosidine synthase and tryptophan decarboxylase on alkaloid production by cell cultures of Catharanthus roseus. J. Gen. Plant Pathol., 79, 414–9.

Tripathi, L., & Tripathi, J. N. (2003). Role of biotechnology in medicinal plants. Tropical Journal of Pharmaceutical Research, 2(2), 243-253.

Valanciene, E., Jonuskiene, I., Syrpas, M., Augustiniene, E., Matulis, P., Simonavicius , A., & Malys , N. (2020). AdvancesandProspectsofPhenolicAcidsProduction, Bioreﬁnery and Analysis. Biomolecules, 874(10).

Valluri, J. V. (2009). Bioreactor Production of Secondary Metabolites from Cell Cultures of Periwinkle and Sandalwood. Methods Mol Biol, 547, 325-35. doi:10.1007/978-1-60327-287-2_26.

Valluri, J. V., Treat, W. J., & Soltes, E. J. (1991). Bioreactor culture of heterotrophic sandalwood (Santalum album L.) cell suspensions utilizing a cell-lift impeller. Plant Cell Rep, 10(6-7), 366-70.

Verdeguer, M., Sánchez-Moreiras, A. M., & Araniti, E. (2020). Phytotoxic Effects and Mechanism of Action of Essential Oils and Terpenoids. Plants, 9, 1571.

Veronese, P., & et al,. (2001). Bioengineering mint crop improvement. Plant Cell Tissue Organ Cult, 64, 133–144.

Verpoorte , R., Van der Heijden , R., Schripsema , J., Hoge , J. H., & Ten Hoopen , H. J. (1993). Plant-cell biotechnology for the production of alkaloids-Present status and prospects. J Nat Prod, 56, 186-207.

Verpoorte, R., Contin, A., & Memelink, J. (2002). Biotechnology for the production of plant secondary metabolite. Phytochem. Rev, 1, 13–25.

Wang , C. W., Oh , M. K., & Liao , J. C. (1999). Engineered isoprenoid pathway enhances astaxanthin production in Escherichia coli. Biotechnol Bioeng, 62, 235-241.

Wang, J., Qian, J., Yao, L., & Lu, Y. (2015). Enhanced production of flavonoids by methyl jasmonate elicitation in cell suspension culture of Hypericum perforatum. Bioresour. Bioprocess, 2, 5.

Wang, X., Zhang, X., Zhang, J., Xiao, L., Zhou, Y., Zhang, Y., . . . Li, X. (2022). Genetic and bioprocess engineering for the selective and high-level production of geranyl acetate in Escherichia coli. ACS Sustain. Chem. Eng, 10, 2881–2889.

Wang, Y., Chen, S., & Yu, O. (2011). Metabolic engineering of flavonoids in plants and microorganisms. Appl. Microbiol. Biotechnol, 91(4), 949-56.

Wani, M., HL.Taylor, Wall, M., Coggon, P., & Mcphail, A. (1971). lant Antitumor Agents.VI.The Isolation and Structure of Taxol, a Novel Antileukemic and Antitumor Agent from Taxus brevifolia. J. Am. Chem. Soc, 93, 2325- 7.

Weston , L. A., & Mathesius, U. (2013). Flavonoids: Their Structure, Biosynthesis and Role in the Rhizosphere, Including Allelopathy. J Chem Ecol, 39, 283–297.

Wildung , M. R., & Croteau , R. (1996). A cDNA clone for taxadiene synthase, the diterpene cyclase that catalyzes the committed step of taxol biosynthesis. J Biol Chem, 271, 9201-9204.

Wu, S. J., Xie, X. G., Feng, K. M., Zhai, X., Ming, Q. L., Qin, L. P., . . . Han, T. (2020). Transcriptome sequencing and signal transduction for the enhanced tanshinone production in Salvia miltiorrhiza hairy roots induced by Trichodermaatroviride D16 polysaccharide fraction. Biosci. Biotechnol. Biochem, 86, zbac088.

Yan, P. (2012). Effects of over-expression of allene oxide cyclase on camptothecin production by cell cultures of Camptotheca acuminata. Afr. J. Biotechnol., 11, 6535–41.

Yancheva, S., Georgieva, L., Badjakov, I., Dincheva, I., Georgieva, M., Georgiev, V., & Kondakova , V. (2018). Application of bioreactor technology in plant propagation and secondary metabolite production. Journal of Central European Agriculture, 20(1), 321- 40. doi:10.5513/JCEA01/20.1.2224

Youseﬁan, S., Lohrasebi, T., Farhadpour, M., & Haghbeen, K. (2020). Effect of methyl jasmonate on phenolic acids accumulation and the expression proﬁle of their biosynthesis-related genes in Mentha spicata hairy root cultures. Plant Cell Tissue Organ Cult, 142, 285–297.

Yun, D. J., Hashimoto, T., & Yamada, Y. (1992). Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition. Proc. Natl. Acad. Sci. USA, 89, 11799–11803.

Zhang , Q., Rich , J. O., Cotterill , I. C., Pantaleone , D. P., & Michels , P. C. (2005). 14-Hydroxylation of opiates: Catalytic direct autoxidation of codeinone to 14-hydroxycodeinone. J Am Chem Soc, 127, 7286-7287.