A review on current conventional and biotechnical approaches to enhance biosynthesis of steviol glycosides in Stevia rebaudiana

Chinese Journal of Chemical Engineering

Volumn 30, Issue , 2021, Pages 92-104

  Basharat, Samra ^a   Huang, Ziyang ^a   Gong, Mengyue ^a   Lv, Xueqin ^a   Ahmed, Aqsa ^a   Hussain, Iftikhar ^a   Li, Jianghua ^a   Du, Guocheng ^a   Liu, Long ^a  

^a JIANGNAN UNIVERSITY   (China)

Author keywords

Biosynthesis; Secondary metabolites; Stevia rebaudiana; Steviol glycosides

Indexed keywords

BEVERAGES; BIOCHEMISTRY; BIOSYNTHESIS; BIOTECHNOLOGY; INTERNATIONAL TRADE; METABOLITES; PLANTS (BOTANY); SUGAR (SUCROSE); SUGAR INDUSTRY; SUGAR SUBSTITUTES;

BIOTECHNOLOGICAL APPROACHES; FOOD AND BEVERAGE INDUSTRY; INTERNATIONAL MARKETS; NATURAL SWEETENER; SECONDARY METABOLITES; STEVIA REBAUDIANA; STEVIA REBAUDIANA BERTONI; STEVIOL GLYCOSIDES;

GLYCOSIDES;

EID: 85101053088     PISSN: 10049541     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cjche.2020.10.018     Document Type: Review

References (123)

1. Moguel-Ordóñez, Y.B., Cabrera-Amaro, D.L., Segura-Campos, M.R., Ruiz-Ruiz, J.C., Studies on drying characteristic, nutritional composition, and antioxidant properties of Stevia rebaudiana (Bertoni) leaves. Int. Agrophys. 29 (2015), 323–331.
2. Philippe, R.N., De Mey, M., Anderson, J., Ajikumar, P.K., Biotechnological production of natural zero-calorie sweeteners. Curr. Opin. Biotechnol. 26 (2014), 155–161.
3. Sharma, S., Walia, S., Singh, B., Kumar, R., Comprehensive review on agro technologies of low-calorie natural sweetener stevia (Stevia rebaudiana Bertoni): a boon to diabetic patients. J. Sci. Food Agric. 96 (2016), 1867–1879.
4. Samsulrizal, N.H., Zainuddin, Z., Noh, A.L., Sundram, T.C., A review of approaches in steviol glycosides synthesis. Int. J. Life Sci. Biotechnol. 2 (2019), 145–157.
5. Ramesh, K., Singh, V., Megeji, N.W., Cultivation of stevia [Stevia rebaudiana (Bert.) Bertoni]: A comprehensive review. Adv. Agron. 89 (2006), 137–177.
6. Yadav, A.K., Singh, S., Dhyani, D., Ahuja, P.S., A review on the improvement of stevia [Stevia rebaudiana (Bertoni)]. Can. J. Plant Sci. 91 (2011), 1–27.
7. Ijaz, M., Pirzada, A.M., Saqib, M., Latif, M., Stevia rebaudiana: An alternative sugar crop in Pakistan–A review. J. Med. Spice Plants. 20 (2015), 88–96.
8. Kazmi, A., Khan, M.A., Mohammad, S., Ali, A., Ali, H., Biotechnological production of natural calorie free steviol glycosides in Stevia rebaudiana: An update on current scenario. Curr. Biotechnol. 8 (2019), 70–84.
9. Megeji, N.W., Kumar, J.K., Singh, V., Kaul, V.K., Ahuja, P.S., Introducing Stevia rebaudiana, a natural zero-calorie sweetener. Curr. Sci., 2005, 801–804.
10. Modi, A., Kumar, N., Conventional and biotechnological approaches to enhance steviol glycosides (SGs) in Stevia rebaudiana Bertoni. Biotechnol. Approaches Med. Aromat. Plants, Springer, 2018, 53–62.
11. Tadhani, M.B., Patel, V.H., Subhash, R., In vitro antioxidant activities of Stevia rebaudiana leaves and callus. J. Food Compos. Anal. 20 (2007), 323–329.
12. Singh, S.D., Rao, G.P., Stevia: The herbal sugar of 21st century. Sugar Tech. 7 (2005), 17–24.
13. Tiwari, S., Stevia rebaudiana: A medicinal and nutraceutical plant and sweet gold for diabetic patients. Int. J. Pharm. Life Sci. 1 (2010), 451–457.
14. Kazmi, A., Khan, M.A., Ali, H., Biotechnological approaches for production of bioactive secondary metabolites in Nigella sativa: An up-to-date review. Int. J. Second. Metab. 6 (2019), 172–195.
15. Huber, B.M., Studies on Stevia (Stevia rebaudiana): Ms.Thesis, North Carolina State University, North Carolina, 2017.
16. King, R.M., The genera of Eupatorieae (Asteraceae). Monogr. Syst., Bot. Missouri Bot Gard. 22 (1987), 1–581.
17. Ceunen, S., Werbrouck, S., Geuns, J.M.C., Stimulation of steviol glycoside accumulation in Stevia rebaudiana by red LED light. J. Plant Physiol. 169 (2012), 749–752.
18. J.D.D. Tamokou, A.T. Mbaveng, V. Kuete, Antimicrobial activities of African medicinal spices and vegetables, Med. Spices Veg. from Africa, Elsevier, Amsterdam, 2017, pp. 207 – 237.
19. Anker, C.C.B., Rafiq, S., Jeppesen, P.B., Effect of steviol glycosides on human health with emphasis on type 2 diabetic biomarkers: a systematic review and meta-analysis of randomized controlled trials. Nutrients, 11, 2019, 1965.
20. Perrier, J.D., Mihalov, J.J., Carlson, S.J., FDA regulatory approach to steviol glycosides. Food Chem. Toxicol. 122 (2018), 132–142.
21. Brandle, J.E., Richman, A., Swanson, A.K., Chapman, B.P., Leaf ESTs from Stevia rebaudiana: A resource for gene discovery in diterpene synthesis. Plant Mol. Biol. 50 (2002), 613–622.
22. Khayam Nekoui, M., Moazam Jazi, M., Mardi, M., Kadkhodaei, S., Development of SSR markers associated with biosynthesis pathway of steviol glycosides in stevia through de novo transcriptome assembly, modares. J. Biotechnol. 11 (2020), 185–191.
23. Lemus-Mondaca, R., Vega-Gálvez, A., Zura-Bravo, L., Ah-Hen, K., Stevia rebaudiana Bertoni, source of a high-potency natural sweetener: a comprehensive review on the biochemical, nutritional and functional aspects. Food Chem. 132 (2012), 1121–1132.
24. Mishra, P., Singh, R., Kumar, U., Prakash, Y.V., Stevia rebaudiana–A magical sweetener. Glob. J. Biotecnol. Biochem. 5 (2010), 62–74.
25. Parris, C.A., Shock, C.C., Qian, M., Dry leaf and steviol glycoside productivity of Stevia rebaudiana in the Western United States. HortScience 51 (2016), 1220–1227.
26. de Oliveira, V.M., Forni-Martins, E.R., Magalhães, P.M., Alves, M.N., Chromosomal and morphological studies of diploid and polyploid cytotypes of Stevia rebaudiana (Bertoni) Bertoni (Eupatorieae, Asteraceae). Genet. Mol. Biol. 27 (2004), 215–222.
27. Metivier, J., Viana, A.N.A.M., The effect of long and short day length upon the growth of whole plants and the level of soluble proteins, sugars, and stevioside in leaves of Stevia rebaudiana Bert. J. Exp. Bot. 30 (1979), 1211–1222.
28. Valio, I.F.M., Rocha, R.F., Effect of photoperiod and growth regulator on growth and flowering of Stevia rebaudiana Bertoni. Japanese J. Crop Sci. 46 (1977), 243–248.
29. Zaidan, L.B.P., Dietrich, S.M.C., Felippe, G.M., Effect of photoperiod on flowering and stevioside content in plants of Stevia rebaudiana Bertoni [sweetness plant], Japanese. J Crop Sci. 49:4 (1980), 569–574.
30. Ceunen, S., Geuns, J.M.C., Steviol glycosides: chemical diversity, metabolism, and function. J. Nat. Prod. 76 (2013), 1201–1228.
31. Olsson, K., Carlsen, S., Semmler, A., Simón, E., Mikkelsen, M.D., Møller, B.L., Microbial production of next-generation stevia sweeteners. Microb. Cell Fact., 15, 2016, 207.
32. Barba, F.J., Criado, M.N., Belda-Galbis, C.M., Esteve, M.J., Rodrigo, D., Stevia rebaudiana Bertoni as a natural antioxidant/antimicrobial for high pressure processed fruit extract: Processing parameter optimization. Food Chem. 148 (2014), 261–267.
33. Pande, S.S., Gupta, P., Plant tissue culture of Stevia rebaudiana (Bertoni): A review. J. Pharmacogn. Phyther. 5 (2013), 26–33.
34. Richman, A., Swanson, A., Humphrey, T., Chapman, R., McGarvey, B., Pocs, R., Brandle, J., Functional genomics uncovers three glucosyltransferases involved in the synthesis of the major sweet glucosides of Stevia rebaudiana. Plant J. 41 (2005), 56–67.
35. Hansen, K.S., Kristensen, C., Tattersall, D.B., Jones, P.R., Olsen, C.E., Bak, S., Møller, B.L., The in vitro substrate regiospecificity of recombinant UGT85B1, the cyanohydrin glucosyltransferase from Sorghum bicolor. Phytochemistry 64 (2003), 143–151.
36. Cacciola, F., Delmonte, P., Jaworska, K., Dugo, P., Mondello, L., Rader, J.I., Employing ultra high pressure liquid chromatography as the second dimension in a comprehensive two-dimensional system for analysis of Stevia rebaudiana extracts. J. Chromatogr. A. 1218 (2011), 2012–2018.
37. Pól, J., Ostrá, E.V., Karásek, P., Roth, M., Benešová, K., Kotlaříková, P., Čáslavský, J., Comparison of two different solvents employed for pressurised fluid extraction of stevioside from Stevia rebaudiana: methanol versus water. Anal. Bioanal. Chem. 388 (2007), 1847–1857.
38. O'Neill, K., Pirro, S., The complete genome sequence of Stevia rebaudiana, the Sweetleaf. F1000Research, 9, 2020, 751.
39. L. Goh, G. Ang, Investigation the Effect of Traditional Chinese Medicine on Stevia Robustness, (n.d.). http://ircset.org/anand/2015papers/IRC-SET-2015_submission_18.pdf.
40. Gardana, C., Scaglianti, M., Simonetti, P., Evaluation of steviol and its glycosides in Stevia rebaudiana leaves and commercial sweetener by ultra-high-performance liquid chromatography-mass spectrometry. J. Chromatogr. A. 1217 (2010), 1463–1470.
41. Khiraoui, A., Hasib, A., Al Faiz, C., Amchra, F., Bakha, M., Boulli, A., Stevia rebaudiana bertoni (honey leaf): A magnificent natural bio-sweetener, biochemical composition, nutritional and therapeutic values. J. Nat. Sci. Res. 7:2017 (2017), 75–85.
42. Savita, S.M., Sheela, K., Sunanda, S., Shankar, A.G., Ramakrishna, P., Stevia rebaudiana–a functional component for food industry. J. Hum. Ecol. 15 (2004), 261–264.
43. Bernal, J., Mendiola, J.A., Ibáñez, E., Cifuentes, A., Advanced analysis of nutraceuticals. J. Pharm. Biomed. Anal. 55 (2011), 758–774.
44. Tona, L., Kambu, K., Mesia, K., Cimanga, K., Apers, S., De Bruyne, T., Pieters, L., Totte, J., Vlietinck, A.J., Biological screening of traditional preparations from some medicinal plants used as antidiarrhoeal in Kinshasa, Congo. Phytomedicine 6 (1999), 59–66.
45. Bharani, A., Ganguly, A., Bhargava, K.D., Salutary effect of Terminalia Arjuna in patients with severe refractory heart failure. Int. J. Cardiol. 49 (1995), 191–199.
46. Abbas Momtazi-Borojeni, A., Esmaeili, S.-A., Abdollahi, E., Sahebkar, A., A review on the pharmacology and toxicology of steviol glycosides extracted from Stevia rebaudiana. Curr. Pharm. Des. 23 (2017), 1616–1622.
47. Kazmi, A., Khan, M.A., Mohammad, S., Ali, A., Kamil, A., Arif, M., Ali, H., Elicitation directed growth and production of steviol glycosides in the adventitious roots of Stevia rebaudiana Bertoni. Ind. Crops Prod., 139, 2019, 111530.
48. Anton, S.D., Martin, C.K., Han, H., Coulon, S., Cefalu, W.T., Geiselman, P., Williamson, D.A., Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 55 (2010), 37–43.
49. Karaköse, H., Jaiswal, R., Kuhnert, N., Characterization and Quantification of Hydroxycinnamate Derivatives in Stevia rebaudiana Leaves by LC-MSn. J. Agric. Food Chem. 59 (2011), 10143–10150.
50. Zohra, F.T., Extraction of secondary metabolites, phytochemical screening and the analysis of antibacterial activity in Stevia rebaudiana. Bs.Thesis, BRAC University, Dhaka, 2015.
51. Yadav, S.K., Guleria, P., Steviol glycosides from Stevia: biosynthesis pathway review and their application in foods and medicine. Crit. Rev. Food Sci. Nutr. 52 (2012), 988–998.
52. Singh, S., Pal, S., Shanker, K., Chanotiya, C.S., Gupta, M.M., Dwivedi, U.N., Shasany, A.K., Sterol partitioning by HMGR and DXR for routing intermediates toward withanolide biosynthesis. Physiol. Plant. 152 (2014), 617–633.
53. Singh, G., Singh, G., Singh, P., Parmar, R., Paul, N., Vashist, R., Swarnkar, M.K., Kumar, A., Singh, S., Singh, A.K., Molecular dissection of transcriptional reprogramming of steviol glycosides synthesis in leaf tissue during developmental phase transitions in Stevia rebaudiana Bert. Sci. Rep. 7 (2017), 1–13.
54. Modi, A., Litoriya, N., Prajapati, V., Rafalia, R., Narayanan, S., Transcriptional profiling of genes involved in steviol glycoside biosynthesis in Stevia rebaudiana bertoni during plant hardening. Dev. Dyn. 243 (2014), 1067–1073.
55. Hatting, M., Tavares, C.D.J., Sharabi, K., Rines, A.K., Puigserver, P., Insulin regulation of gluconeogenesis. Ann. N. Y. Acad. Sci., 1411, 2018, 21.
56. S.R. Lucho, M.N. do Amaral, C. Milech, M.Á. Ferrer, A.A. Calderón, V.J. Bianchi, E.J.B. Braga, Elicitor-induced transcriptional changes of genes of the steviol glycoside biosynthesis pathway in Stevia rebaudiana Bertoni, J. Plant Growth Regul. 37 (2018) 971–985.
57. Ohto, C., Muramatsu, M., Obata, S., Sakuradani, E., Shimizu, S., Prenyl alcohol production by expression of exogenous isopentenyl diphosphate isomerase and farnesyl diphosphate synthase genes in Escherichia coli. Biosci. Biotechnol. Biochem. 73:1 (2009), 186–188.
58. Mathur, S., Bulchandani, N., Parihar, S., Shekhawat, G.S., Critical review on steviol glycosides: pharmacological, toxicological and therapeutic aspects of high potency zero caloric sweetener. Int. J. Pharmacol. 13 (2017), 916–928.
59. Karimi, R., Vahedi, M., Pourmazaheri, H., Balilashaki, K., Biotechnological approaches in Stevia rebaudiana and its therapeutic applications. Adv. Biomed. Pharm. 4 (2017), 31–43.
60. Brandle, J.E., Telmer, P.G., Steviol glycoside biosynthesis. Phytochemistry 68 (2007), 1855–1863.
61. Wanke, M., Skorupinska-Tudek, K., Swiezewska, E., Isoprenoid biosynthesis via 1-deoxy-D-xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DOXP/MEP) pathway. Acta Biochim. Pol. 48 (2001), 663–672.
62. Sharma, M., Thakral, N.K., Thakral, S., Chemistry and in vivo profile of ent-kaurene glycosides of Stevia rebaudiana bertoni—An overview. Natural Product Radiance 8:2 (2009), 181–189.
63. Tadhani, M.B., Subhash, R., In vitro antimicrobial activity of Stevia rebaudiana Bertoni leaves. Trop. J. Pharm. Res. 5 (2006), 557–560.
64. Boonkaewwan, C., Toskulkao, C., Vongsakul, M., Anti-inflammatory and immunomodulatory activities of stevioside and its metabolite steviol on THP-1 cells. J. Agric. Food Chem. 54 (2006), 785–789.
65. Nikiforov, A.I., Eapen, A.K., A 90-day oral (dietary) toxicity study of rebaudioside A in Sprague-Dawley rats. Int. J. Toxicol. 27 (2008), 65–80.
66. Mauri, P., Catalano, G., Gardana, C., Pietta, P., Analysis of Stevia glycosides by capillary electrophoresis. Electrophoresis 17 (1996), 367–371.
67. Brandle, J.E., Starratt, A.N., Gijzen, M., Stevia rebaudiana: Its agricultural, biological, and chemical properties. Can. J. Plant Sci. 78 (1998), 527–536.
68. Goyal, S.K., Samsher, G.R.K., Goyal, R.K., Stevia (Stevia rebaudiana) a bio-sweetener: A review. Int J Food Sci Nutr. 61 (2010), 1–10.
69. Kolb, N., Herrera, J.L., Ferreyra, D.J., Uliana, R.F., Analysis of sweet diterpene glycosides from Stevia rebaudiana: Improved HPLC method. J. Agric. Food Chem. 49 (2001), 4538–4541.
70. Reis, M.H.M., Da Silva, F.V., Andrade, C.M.G., Rezende, S.L., Wolf Maciel, M.R., Bergamasco, R., Clarification and purification of aqueous stevia extract using membrane separation process. J. Food Process Eng. 32 (2009), 338–354.
71. Hearn, L.K., Subedi, P.P., Determining levels of steviol glycosides in the leaves of Stevia rebaudiana by near infrared reflectance spectroscopy. J. Food Compos. Anal. 22 (2009), 165–168.
72. Chao, Y.Y., Chen, Y.L., Lin, H.Y., Huang, Y.L., Rapid screening of basic colorants in processed vegetables through mass spectrometry using an interchangeable thermal desorption electrospray ionization source. Anal. Chim. Acta. 1010 (2018), 44–53.
73. Liu, J., Li, J., Tang, J., Ultrasonically assisted extraction of total carbohydrates from Stevia rebaudiana Bertoni and identification of extracts. Food Bioprod. Process. 88 (2010), 215–221.
74. Geuns, J.M.C., Stevioside. Phytochemistry 64 (2003), 913–921.
75. Koyama, E., Sakai, N., Ohori, Y., Kitazawa, K., Izawa, O., Kakegawa, K., Fujino, A., Ui, M., Absorption and metabolism of glycosidic sweeteners of stevia mixture and their aglycone, steviol, in rats and humans. Food Chem. Toxicol. 41 (2003), 875–883.
76. Aman, N., Hadi, F., Khalil, S.A., Zamir, R., Ahmad, N., Efficient regeneration for enhanced steviol glycosides production in Stevia rebaudiana (Bertoni). C. R. Biol. 336 (2013), 486–492.
77. Richman, A.S., Gijzen, M., Starratt, A.N., Yang, Z., Brandle, J.E., Diterpene synthesis in Stevia rebaudiana: recruitment and up-regulation of key enzymes from the gibberellin biosynthetic pathway. Plant J. 19 (1999), 411–421.
78. Kim, K.K., Sawa, Y., Shibata, H., Hydroxylation ofent-Kaurenoic Acid to Steviol inStevia rebaudianaBertoni—Purification and Partial Characterization of the Enzyme. Arch. Biochem. Biophys. 332 (1996), 223–230.
79. Yoneda, Y., Nakashima, H., Miyasaka, J., Ohdoi, K., Shimizu, H., Impact of blue, red, and far-red light treatments on gene expression and steviol glycoside accumulation in Stevia rebaudiana. Phytochemistry 137 (2017), 57–65.
80. Wang, Y., Chen, L., Li, Y., Li, Y., Yan, M., Chen, K., Hao, N., Xu, L., Efficient enzymatic production of rebaudioside A from stevioside. Biosci. Biotechnol. Biochem. 80 (2016), 67–73.
81. Moon, J.H., Lee, K., Lee, J.H., Lee, P.C., Redesign and reconstruction of a steviol-biosynthetic pathway for enhanced production of steviol in Escherichia coli. Microb. Cell Fact., 19, 2020, 20.
82. Zhang, S., Chen, H., Xiao, J., Liu, Q., Xiao, R., Wu, W., Mutations in the uridine diphosphate glucosyltransferase 76G1 gene result in different contents of the major steviol glycosides in Stevia rebaudiana. Phytochemistry 162 (2019), 141–147.
83. Wang, J., Li, S., Xiong, Z., Wang, Y., Pathway mining-based integration of critical enzyme parts for de novo biosynthesis of steviolglycosides sweetener in Escherichia coli. Cell Res. 26 (2016), 258–261.
84. Bayraktar, M., Naziri, E., Karabey, F., Akgun, I.H., Bedir, E., Röck-Okuyucu, B., Gürel, A., Enhancement of stevioside production by using biotechnological approach in in vitro culture of Stevia rebaudiana. Int. J. Second. Metab. 5 (2018), 362–374.
85. Bayraktar, M., Naziri, E., Karabey, F., Akgun, I.H., Bedir, E., Bärbel, R.-O., Gürel, A., Enhancement of stevioside production by using biotechnological approach in in vitro culture of Stevia rebaudiana. Int. J. Second. Metab. 5 (2018), 362–374.
86. Pandey, M., Chikara, S.K., In vitro regeneration and effect of abiotic stress on physiology and biochemical content of Stevia rebaudiana Bertoni. J. Plant Sci. Res., 1, 2014, 113.
87. Khalil, S.A., Zamir, R., Ahmad, N., Effect of different propagation techniques and gamma irradiation on major steviol glycoside's content in Stevia rebaudiana. J. Anim. Plant Sci. 24 (2014), 1743–1751.
88. Khalil, S.A., Zamir, R., Ahmad, N., Effect of different propagation techniques and gamma irradiation on major steviol glycoside's content in Stevia rebaudiana. Jouranl of Animal and Plant 24:6 (2014), 1743–1751.
89. Rameshsing, C.N., Hegde, S.N., Vasundhara, M., Enhancement of steviol glycosides in stevia (Stevia rebaudiana Bertoni) through induction of polyploidy. Curr. Trends Biotechnol. Pharm. 9 (2015), 141–146.
90. Ishikawa, H., Kitahata, S., Ohtani, K., Tanaka, K., Transfructosylation of Rebaudioside A (a Sweet Glycoside of Stevial Leaves) with Microbacterium β-Fructofuranosidase. Chem. Pharm. Bull. 39 (1991), 2043–2045.
91. Bender, C., Graziano, S., Zimmermann, B.F., Study of Stevia rebaudiana Bertoni antioxidant activities and cellular properties. Int. J. Food Sci. Nutr. 66 (2015), 553–558.
92. de Oliveira, B.H., Packer, J.F., Chimelli, M., de Jesus, D.A., Enzymatic modification of stevioside by cell-free extract of Gibberella fujikuroi. J. Biotechnol. 131 (2007), 92–96.
93. Gupta, P., Sharma, S., Saxena, S., Biomass yield and steviol glycoside production in callus and suspension culture of Stevia rebaudiana treated with proline and polyethylene glycol. Appl. Biochem. Biotechnol. 176 (2015), 863–874.
94. Khalil, S.A., Zamir, R., Ahmad, N., Selection of suitable propagation method for consistent plantlets production in Stevia rebaudiana (Bertoni). Saudi J. Biol. Sci. 21 (2014), 566–573.
95. Thiyagarajan, M., Venkatachalam, P., Large scale in vitro propagation of Stevia rebaudiana (bert) for commercial application: Pharmaceutically important and antidiabetic medicinal herb. Ind. Crops Prod. 37 (2012), 111–117.
96. Das, A., Gantait, S., Mandal, N., Ahmed, M.B., Salahin, M., Karim, R., Razvy, M.A., Hannan, M.M., Anbajhagan, M., Kalpana, M., Clonal propagation of Stevia rebaudiana bert through axillary shoot proliferation in vitro. Int. J. Agric. Res. 6 (2007), 121–125.
97. Thakur, M., Bhattacharya, S., Khosla, P.K., Puri, S., Improving production of plant secondary metabolites through biotic and abiotic elicitation. J. Appl. Res. Med. Aromat. Plants. 12 (2019), 1–12.
98. Khan, T., Abbasi, B.H., Khan, M.A., Azeem, M., Production of biomass and useful compounds through elicitation in adventitious root cultures of Fagonia indica. Ind. Crops Prod. 108 (2017), 451–457.
99. Golkar, P., Moradi, M., Garousi, G.A., Elicitation of Stevia glycosides using salicylic acid and silver nanoparticles under callus culture. Sugar Tech. 21 (2019), 569–577.
100. Tahmasi, S., Garoosi, G., Ahmadi, J., Farjaminezhad, R., Effect of salicylic acid on stevioside and rebaudioside A production and transcription of biosynthetic genes in in vitro culture of Stevia rebaudiana. Iran. J. Genet. Plant Breed. 6 (2017), 1–8.
101. Vafadar, F., Amooaghaie, R., Otroshy, M., Effects of plant-growth-promoting rhizobacteria and arbuscular mycorrhizal fungus on plant growth, stevioside, NPK, and chlorophyll content of Stevia rebaudiana. J. Plant Interact. 9 (2014), 128–136.
102. Das, K., Dang, R., Influence of biofertilizers on stevioside content in Stevia rebaudiana grown in acidic soil condition. Arch. Appl. Sci. Res. 2 (2010), 44–49.
103. Abdullateef, R.A., Bin Osman, M., Bint Zainuddin, Z., Acclimatized apparatus enhanced seed germination in Stevia rebaudiana Bertoni. Int. J. Biol., 7, 2015, 28.
104. G.B. Pigatto, E.N. Gomes, J. de C. Tomasi, A.P. Ferriani, C. Deschamps, Effects of indolebutyric acid, stem cutting positions and substrates on the vegetative propagation of stevia rebaudiana bertoni,Revista Colombiana de Ciencias Hortícolas 12(1)(2018)202-211.
105. A. Martini, S. Tavarini, M. Macchia, G. Benelli, D. Romano, A. Canale, L.G. Angelini, Floral phenology, insect pollinators and seed quality of 36 genotypes of Stevia rebaudiana Bert. cultivated in Italy, in: Stevia Growth Knowl. Tast., EUSTAS, 2015, pp. 13–26.
106. Gupta, P., Sharma, S., Saxena, S., Callusing in Stevia rebaudiana (natural sweetener) for steviol glycoside production. Int. J. Agric. Biol. Sci. 1 (2010), 30–34.
107. Khan, M.A., Khan, T., Ali, H., Plant cell culture strategies for the production of terpenes as green solvents. Ind. Appl. Green Solvents I:50 (2019), 1–20.
108. Ali, A., Mohammad, S., Khan, M.A., Raja, N.I., Arif, M., Kamil, A., Mashwani, Z.-R., Silver nanoparticles elicited in vitro callus cultures for accumulation of biomass and secondary metabolites in Caralluma tuberculata. Artif. Cells, Nanomed., Biotechnol. 47 (2019), 715–724.
109. Banerjee, M., Sarkar, P., In vitro callusing in Stevia rebaudiana Bertoni using cyanobacterial media-a novel approach to tissue culture. Int. J. Integr. Biol. 3 (2008), 163–168.
110. Murrashige, T., Skoog, F., A revised medium for rapid growth and bioassays with tobacco tissue culture. Physiol. Plant. 15 (1962), 473–497.
111. Pandey, H., Pandey, P., Pandey, S.S., Singh, S., Banerjee, S., Meeting the challenge of stevioside production in the hairy roots of Stevia rebaudiana by probing the underlying process. Plant Cell, Tissue Organ Cult. 126 (2016), 511–521.
112. Wang, J., Li, J., Li, J., Li, J., Liu, S., Huang, L., Gao, W., Production of active compounds in medicinal plants: from plant tissue culture to biosynthesis. Chinese Herb. Med. 9 (2017), 115–125.
113. Punja, Z.K., Genetic engineering of plants to enhance resistance to fungal pathogens—A review of progress and future prospects. Can. J. Plant Pathol. 23 (2001), 216–235.
114. Sher Khan, R., Iqbal, A., Malak, R., Shehryar, K., Attia, S., Ahmed, T., Ali Khan, M., Arif, M., Mii, M., Plant defensins: types, mechanism of action and prospects of genetic engineering for enhanced disease resistance in plants. 3 Biotech., 9, 2019, 192.
115. Broun, P., Transcription factors as tools for metabolic engineering in plants. Curr. Opin. Plant Biol. 7 (2004), 202–209.
116. Wu, Q., La Hovary, C., Chen, H.-Y., Li, X., Eng, H., Vallejo, V., Qu, R., Dewey, R.E., An efficient Stevia rebaudiana transformation system and in vitro enzyme assays reveal novel insights into UGT76G1 function. Sci. Rep. 10 (2020), 1–14.
117. M. Mubarak, Y. El Halmouch, A. Belal, Ma. Elfadeel, Tn. EL-Din, S.F. Mahmoud, M.E. El Sharnouby, E. El Sarag, Improving sweet leaf ('Stevia rebaudiana'var. Bertoni) resistance to bialaphos herbicide via'bar’gene transfer, Plant Omics. 8 (2015) 232.
118. Deligiannidou, G.-E., Philippou, E., Vidakovic, M., Berghe, W.V., Heraclides, A., Grdovic, N., Mihailovic, M., Kontogiorgis, C., Natural products derived from the mediterranean diet with antidiabetic activity: from insulin mimetic hypoglycemic to nutriepigenetic modulator compounds. Curr. Pharm. Des. 25 (2019), 1760–1782.
119. Ibrahim, I.A., Nasr, M.I., Mohammedm, B.R., El-Zefzafi, M.M., Nutrient factors affecting in vitro cultivation of Stevia rebaudiana. Sugar Tech. 10 (2008), 248–253.
120. Chester, K., Tamboli, E.T., Parveen, R., Ahmad, S., Genetic and metabolic diversity in Stevia rebaudiana using RAPD and HPTLC analysis. Pharm. Biol. 51 (2013), 771–777.
121. Heikal, A.H., Badawy, O.M., Hafez, A.M., Genetic relationships among some Stevia (Stevia rebaudiana Bertoni) accessions based on ISSR analysis. Res. J. Cell Mol. Biol. 2 (2008), 1–5.
122. Navarrete, C., Jacobsen, I.H., Martínez, J.L., Procentese, A., Cell factories for industrial production processes: Current issues and emerging solutions. Processes. 2:1 (2008), 1–5.
123. Xiang, Z., Tang, X., Liu, W., Song, C., A comparative morphological and transcriptomic study on autotetraploid Stevia rebaudiana (bertoni) and its diploid. Plant Physiol. Biochem. 143 (2019), 154–164.