Bioreactor configurations for adventitious root culture: recent advances toward the commercial production of specialized metabolites

References

• Erb M, Kliebenstein DJ. Plant secondary metabolites as defenses, regulators, and primary metabolites: the blurred functional dichotomy. Plant Physiol. 2020;184:39–52. doi:10.1104/pp.20.00433.
   PubMed Web of Science ®Google Scholar
• Kessler A, Kalske A. Plant secondary metabolite diversity and species interactions. Annu Rev Ecol Evol Syst. 2018;49:115–138. doi:10.1146/annurev-ecolsys-110617-062406.
   Web of Science ®Google Scholar
• Wink M. Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry. 2003;64:3–19. doi:10.1016/s0031-9422(03)00300-5.
   PubMed Web of Science ®Google Scholar
• Jamwal K, Bhattacharya S, Puri S. Plant growth regulator mediated consequences of secondary metabolites in medicinal plants. J Appl Res Med Aromat Plants. 2018;9:26–38. doi:10.1016/j.jarmap.2017.12.003.
   Web of Science ®Google Scholar
• Hartmann T. From waste products to ecochemicals: fifty years research of plant secondary metabolites. Phytochemistry. 2007;68:2831–2846. doi:10.1016/j.phytochem.2007.09.017.
   PubMed Web of Science ®Google Scholar
• Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr. 2011;2:32–50. doi:10.3945/an.110.000117.
   PubMed Web of Science ®Google Scholar
• Heinrich M, Mah J, Amirkia V. Alkaloids used as medicines: structural phytochemistry meets biodiversity: an update and forward look. Molecules. 2021;26:1836. doi:10.3390/molecules26071836.
   PubMed Web of Science ®Google Scholar
• Courdavault V, O'Connor SE, Oudin A, et al. Towards the microbial production of plant-derived anticancer drugs. Trends Cancer. 2020;6:444–448. doi:10.1016/j.trecan.2020.02.004.
   PubMed Web of Science ®Google Scholar
• Jugran AK, Rawat S, Devkota HP, et al. Diabetes and plant-derived natural products: from ethnopharmacological approaches to their potential for modern drug discovery and development. Phytother Res. 2021;35:223–245. doi:10.1002/ptr.6821.
   PubMed Web of Science ®Google Scholar
• Li N, Wang Q, Zhou J, et al. Insight into the progress on natural dyes: sources, structural features, health effects, challenges, and potential. Molecules. 2022;27:3291. doi:10.3390/molecules27103291.
   PubMed Web of Science ®Google Scholar
• Sharmeen J, Mahomoodally F, Zengin G, et al. Essential oils as natural sources of fragrance compounds for cosmetics and cosmeceuticals. Molecules. 2021;26:666. doi:10.3390/molecules26030666.
   PubMed Web of Science ®Google Scholar
• Lybrand DB, Xu H, Last RL, et al. How plants synthesize pyrethrins: safe and biodegradable insecticides. Trends Plant Sci. 2020;25:1240–1251. doi:10.1016/j.tplants.2020.06.012.
   PubMed Web of Science ®Google Scholar
• Kilani-Morakchi S, Morakchi-Goudjil H, Sifi K. Azadirachtin-based insecticide: overview, risk assessments, and future directions. Front. Agron. 2021;3:676208. doi:10.3389/fagro.2021.676208.
   Google Scholar
• Motolinía-Alcántara EA, Castillo-Araiza CO, Rodríguez-Monroy M, et al. Engineering considerations to produce bioactive compounds from plant cell suspension culture in bioreactors. Plants. 2021;10:2762. doi:10.3390/plants10122762.
   Google Scholar
• Dalawai D, Aware C, Jadhav JP, et al. RP-HPLC analysis of diterpene lactones in leaves and stem of different species of Andrographis. Nat Prod Res. 2021;35:2239–2242. doi:10.1080/14786419.2019.1662004.
   PubMed Web of Science ®Google Scholar
• Ishikawa H, Colby DA, Seto S, et al. Total synthesis of vinblastine, vincristine, related natural products, and key structural analogues. J Am Chem Soc. 2009;131:4904–4916. doi:10.1021/ja809842b.
   PubMed Web of Science ®Google Scholar
• Li Y, Kong D, Fu Y, et al. The effect of developmental and environmental factors on secondary metabolites in medicinal plants. Plant Physiol Biochem. 2020;148:80–89. doi:10.1016/j.plaphy.2020.01.006.
   PubMed Web of Science ®Google Scholar
• Nosov AM. Application of cell technologies for production of plant-derived bioactive substances of plant origin. Appl Biochem Microbiol. 2012;48:609–624. doi:10.1134/S000368381107009X.
   Web of Science ®Google Scholar
• Li TSC, Mazza G. Correlation between leaf and soil mineral concentrations and ginsenoside contents in American ginseng. Hort Sci. 1999;34:85–87. doi:10.21273/HORTSCI.34.1.85.
   Google Scholar
• Balandrin MF, Klocke JA, Wurtele ES, et al. Natural plant chemicals: sources of industrial and medicinal materials. Science. 1985;228:1154–1160. doi:10.1126/science.3890182.
   PubMed Web of Science ®Google Scholar
• Charlwood BV, Charlwood KA. Terpenoid production in plant cell culture. Harborne, JB, Tomas-Barberan F, editors. Ecological chemistry and biochemistry of plant terpenoids. Oxford (New York): Clarendon Press; 1991; p. 95–132.
   Google Scholar
• Nail MC, Roberts SC. Flow cytometric identification of paclitaxel-accumulating subpopulations. Biotechnol Prog. 2005;21:978–983. doi:10.1021/bp049544l.
   PubMed Web of Science ®Google Scholar
• Sánchez-Sampedro MA, Fernández-Tárrago J, Corchete P. Elicitation of Silybum marianum: effect of subculture and repeated addition of methyl jasmonate. Biotechnol Lett. 2009;31:1633–1637. doi:10.1007/s10529-009-0043-0.
   PubMed Web of Science ®Google Scholar
• Wilson SA, Roberts SC. Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules. Plant Biotechnol J. 2012;10:249–268. doi:10.1111/j.1467-7652.2011.00664.x.
   PubMed Web of Science ®Google Scholar
• Giri A, Narasu ML. Transgenic hairy roots: recent trends and applications. Biotechnol Adv. 2000;18:1–22. doi:10.1016/s0734-9750(99)00016-6.
   PubMed Web of Science ®Google Scholar
• Murthy HN, Hahn EJ, Paek KY. Adventitious roots and secondary metabolism. Sheng Wu Gong Cheng Xue Bao. 2008;24:711–716. doi:10.1016/s1872-2075(08)60035-7.
   PubMedGoogle Scholar
• Murthy HN, Dandin VS, Paek KY. Tools for biotechnological production of useful phytochemicals from adventitious root cultures. Phytochem Rev. 2016;15:129–145. doi:10.1007/s11101-014-9391-z.
   Web of Science ®Google Scholar
• Srivastava S, Srivastava AK. Hairy root culture for mass-production of high-value secondary metabolites. Crit Rev Biotechnol. 2007;27:29–43. doi:10.1080/07388550601173918.
   PubMed Web of Science ®Google Scholar
• Devi J, Kumar R, Singh K, et al. In vitro adventitious roots: a non-disruptive technology for the production of phytoconstituents on the industrial scale. Crit Rev Biotechnol. 2021;41:564–579. doi:10.1080/07388551.2020.1869690.
   PubMed Web of Science ®Google Scholar
• Hussain MJ, Abbas Y, Nazli N, et al. Root cultures, a boon for the production of valuable compounds: a comprehensive review. Plants. 2022;11:439. doi:10.3390/plants11030439.
   Google Scholar
• Krasteva G, Georgiev V, Pavlov A. Recent applications of plant cell culture technology in cosmetics and foods. Eng Life Sci. 2021;21:68–76. doi:10.1002/elsc.202000078.
   PubMed Web of Science ®Google Scholar
• Titova MV, Popova EV, Konstantinova SV, et al. Suspension cell culture of Diosacoarea deltoidea-A renewable source of biomass and furostanol glycosides for food and pharmaceutical industry. Agronomy. 2021;11:394. doi:10.3390/agronomy11020394.
   Google Scholar
• Kartnig T, Göbel I, Heydel B. Production of hypericin, pseudophyericin, and flavonoids in cell cultures of various Hypericum species and their chemotypes. Planta Med. 1996;62:51–53. doi:10.1055/s-2006-957796.
   PubMed Web of Science ®Google Scholar
• Cui X-H, Chakrabarty D, Lee E-J, et al. Production of adventitious roots and secondary metabolites by Hypericum perforatum L. in a bioreactor. Bioresour Technol. 2010;101:4708–4716. doi:10.1016/j.biortech.2010.01.115.
   PubMed Web of Science ®Google Scholar
• Komaraiah P, Kavi Kishor PB, Carlsson M, et al. Enhancement of anthraquinone accumulation in Morinda citrifolia suspension cultures. Plant Sci. 2005;168:1337–1344. doi:10.1016/j.plantsci.2005.01.017.
   Web of Science ®Google Scholar
• Baque MA, Murthy HN, Paek KY. Adventitious root culture of Morinda citrifolia in bioreactors for production of bioactive compounds. Paek KY, Murthy HN, Zhong JJ, editors. Production of biomass and bioactive compounds using bioreactor technology. Dordrecht (The Netherlands): Springer Science Business Media; 2014; p. 185–222.
   Google Scholar
• Deepthi S, Satheeshkumar K. Enhanced camptothecin production induced by elicitors in the cell suspension cultures of Ophiorrhiza mungos Linn. Plant Cell Tiss Organ Cult. 2016;124:483–493. doi:10.1007/s11240-015-0908-y.
   Web of Science ®Google Scholar
• Deepthi S, Satheeshkumar S. Effect of major nutrients, growth regulators and inoculum size on enhanced growth and camptothecin production in adventitious root cultures of Ophiorrhiza mungos L. Biochem Eng J. 2017;117:198–209. doi:10.1016/j.bej.2016.10.016.
   Web of Science ®Google Scholar
• Lee JD, Le KC, Park YK, et al. Cell culture system versus adventitious root culture system in Asian and American ginseng: a collation. Plant Cell Tiss Organ Cult. 2018;132:295–302. doi:10.1007/s11240-017-1329-x.
   Web of Science ®Google Scholar
• Murthy HN, Kim YS, Jeong CS, et al. Production of ginsenosides from adventitious root cultures of Panax ginseng. Paek KY, Murthy HN, Zhong JJ, editors. Production of biomass and bioactive compounds using bioreactor technology. Dordrecht (The Netherlands): Springer Science Business Media; 2014; p. 625–651.
   Google Scholar
• Murthy HN, Georgiev MI, Kim YS, et al. Ginsenosides: prospective for sustainable biotechnological production. Appl Microbiol Biotechnol. 2014;98:6243–6254. doi:10.1007/s00253-014-5801-9.
   PubMed Web of Science ®Google Scholar
• Murthy HN, Dandin VS, Park S-Y, et al. Quality, safety and efficacy of ginseng adventitious roots produced in vitro. Appl Microbiol Biotechnol. 2018;102:7309–7317. doi:10.1007/s00253-018-9188-x.
   PubMed Web of Science ®Google Scholar
• Chattopadhyay S, Srivastava AK, Bhojwani SS, et al. Development of suspension culture of Podophyllum hexandrum for production of podophyllotoxin. Biotechnol Lett. 2001;23:2063–2066. doi:10.1023/A:1013704116860.
   Web of Science ®Google Scholar
• Rajesh M, Sivanandhan G, Arun M, et al. Factors influencing podophyllotoxin production in adventitious root cultures of Podophyllum hexandrum Royle. Acta Physiol Plant. 2014;36:1009–1021. doi:10.1007/s11738-013-1479-3.
   Web of Science ®Google Scholar
• Anbazhagan VR, Ahn CH, Harada E, et al. Podophyllotoxin production via cell and adventitious root cultures of Podophyllum peltatum. In Vitro Cell Dev Biol Plant. 2008;44:494–501. doi:10.1007/s11627-008-9134-1.
   Web of Science ®Google Scholar
• Wink M. Genes of secondary metabolism: differential expression in plants and in vitro cultures and functional expression in genetically transformed microorganisms. Kurz, WGW, editor. Primary and secondary metabolism in plant cell cultures. Heidelberg (Germany): Springer-Verlag; 1989; p. 239–251.
   Google Scholar
• Leathers RR, Smith MAL, Aitken-Christie J. Automation of the bioreactor process for mass propagation and secondary metabolism. Aitken-Christie A, Kozai T, Smith, MAL, editors. Automation and environmental control in plant tissue culture. Dordrecht (The Netherlands): Springer; 1995; p. 124–187.
   Google Scholar
• Werner S, Maschke RW, Eibl D, et al. Bioreactor technology for sustainable production of plant cell-derived products. Pavlov A, Bley T, editors. Bioprocessing of plant in vitro systems. Reference Series in Phytochemistry. Cham: Springer; 2018; p. 413–432.
   Google Scholar
• Eibl R, Eibl D. Design of bioreactors suitable for plant cell and tissue cultures. Phytochem Rev. 2008;7:593–598. doi:10.1007/s11101-007-9083-z.
   Google Scholar
• Georgiev V, Schumann A, Pavlov A, et al. Temporary immersion systems in plant biotechnology. Eng. Life Sci. 2014;14:607–621. doi:10.1002/elsc.201300166.
   Web of Science ®Google Scholar
• Georgiev MI, Eibl R, Zhong JJ. Hosting the plant cells in vitro: recent trends in bioreactors. Appl Microbiol Biotechnol. 2013;97:3787–3800. doi:10.1007/s00253-013-4817-x.
   PubMed Web of Science ®Google Scholar
• Georgiev MI. Design of bioreactors for plant cell organ cultures. Paek KY, Murthy HN, Zhong JJ, editors. Production of biomass and bioactive compounds using bioreactor technology. Cham: Springer; 2014; p. 3–14.
   Google Scholar
• Huang TK, McDonald KA. Bioreactor engineering for recombinant protein production in plant cell suspension cultures. Biochem Eng J. 2009;45:168–184. doi:10.1016/j.bej.2009.02.008.
   Web of Science ®Google Scholar
• Kim YJ, Wyslouzil BE, Weathers PJ. Secondary metabolism of hairy root cultures in bioreactors. In Vitro Cell Dev Biol. Plant. 2002;38:1–10. doi:10.1079/IVP2001243.
   Web of Science ®Google Scholar
• Steingroewer J, Bley T, Georgiev V, et al. Bioprocessing of differentiated plant in vitro systems. Eng Life Sci. 2013;13:26–38. doi:10.1002/elsc.201100226.
   Web of Science ®Google Scholar
• Valdiani A, Hansen OK, Nielsen UB, et al. Bioreactor-based advances in plant tissue and cell culture: challenges and prospects. Crit Rev Biotechnol. 2019;39:20–34. doi:10.1080/07388551.2018.1489778.
   Web of Science ®Google Scholar
• Huang TK, McDonald KA. Bioreactor systems for in vitro production of foreign proteins using plant cell cultures. Biotechnol Adv. 2012;30:398–409. doi:10.1016/j.biotechadv.2011.07.016.
   PubMed Web of Science ®Google Scholar
• Barragan LP, Figueroa J, Duran LR, et al. Fermentative production methods. Amsterdam (Germany): Elsevier; 2016; p. 189–217.
   Google Scholar
• Choi Y, Kim Y, Paek KY. Types and designs of bioreactors for hairy root culture. Gupta, SD, Ibaraki Y, editors. Plant tissue culture engineering. Dordrecht (The Netherlands): Springer; 2006; p. 161–172.
   Google Scholar
• Fitzpatrick JJ. Insights from mathematical modeling into energy requirement and process design of continuous and batch-stirred tank aerobic bioreactors. Chem Eng. 2019;3:65.
   Google Scholar
• Esperanca MN, Mendes CE, Rodriguez GY, et al. Sprager design as key parameter to define shear conditions in pneumatic bioreactors. Biochem Eng J. 2020;157:107529. doi:10.1016/j.bej.2020.107529.
   Web of Science ®Google Scholar
• Kumar N, Gupta R, Bansal A. Effect of surface tension on hydrodynamics and mass transfer coefficient in airlift reactors. Chem Eng Technol. 2020;43:995–1004. doi:10.1002/ceat.201900271.
   Web of Science ®Google Scholar
• Eibl R, Werner S, Eibl D. Disposable bioreactors for plant liquid cultures at liter-scale: review. Eng Life Sci. 2009;9:156–164. doi:10.1002/elsc.200800102.
   Web of Science ®Google Scholar
• Eibl R, Kaiser S, Lombriser R, et al. Disposable bioreactors: the current state-of-the-art and recommended applications in biotechnology. Appl Microbiol Biotechnol. 2010;86:41–49. doi:10.1007/s00253-009-2422-9.
   PubMed Web of Science ®Google Scholar
• Buchs J. Introduction to advantages and problems of shake cultures. Biochem Eng J. 2001;7:91–98. doi:10.1016/S1369-703X(00)00106-6.
   PubMed Web of Science ®Google Scholar
• Suresh S, Srivastava VC, Mishra IM. Critical analysis of engineering aspects of shaken flask bioreactors. Crit Rev Biotechnol. 2009;29:255–278. doi:10.3109/07388550903062314.
   PubMed Web of Science ®Google Scholar
• Kuźma Ł, Bruchajzer E, Wysokińska H. Methyl jasmonate effect on diterpenoid accumulation in Salvia sclarea hairy root culture in shake flasks and sprinkle bioreactor. Enzyme Microb Tech. 2009;44:406–410. doi:10.1016/j.enzmictec.2009.01.005.
   Web of Science ®Google Scholar
• Choi SM, Son SH, Yun SR, et al. Pilot scale culture of adventitious roots of ginseng in a bioreactor system. Plant Cell Tissue Organ Cult. 2000;62:187–193. doi:10.1023/A:1006412203197.
   Web of Science ®Google Scholar
• Kusakari K, Yokoyama M, Inomata S, et al. Large-scale production of saikosaponins through root culturing of Bupleurum falcatum L. using modified airlift rectors. J Biosci Bioeng. 2012;113:99–105. doi:10.1016/j.jbiosc.2011.08.019.
   PubMed Web of Science ®Google Scholar
• Woo SH, Park JM. Root culture using a mist culture system and estimation of scale-up feasibility. J Chem Tech Biotechnol. 1996;66:355–362.
   Google Scholar
• Ruffoni B, Pistelli L, Bertoli A, et al. Plant cell cultures: bioreactors for industrial production. Adv Exp Med Biol. 2010;698:203–221. doi:10.1007/978-1-4419-7347-4_15.
   PubMed Web of Science ®Google Scholar
• Min JY, Jung HY, Kang SM, et al. Production of tropane alkaloids by small-scale bubble column bioreactor cultures of Scopolia parvifloara adventitious roots. Bioresour Technol. 2007;98:1748–1753. doi:10.1016/j.biortech.2006.07.033.
   PubMed Web of Science ®Google Scholar
• Jeong G-T, Park D-H, Hwang B, et al. Comparison of growth characteristics of Panax ginseng hairy roots in various bioreactors. ABAB. 2003;107:493–504. doi:10.1385/ABAB:107:1-3:493.
   Google Scholar
• Shin KS, Murthy HN, Ko JY, et al. Growth and betacyanin production by hairy roots of Beta vulgaris in airlift bioreactors. Biotechnol Lett. 2002;24:2067–2069. doi:10.1023/A:1021383807949.
   Web of Science ®Google Scholar
• Paek KY, Murthy HN, Hahn EJ, et al. Large-scale culture of ginseng adventitious roots for production of ginsenosides. Adv Biochem Eng Biotechnol. 2009;113:151–176.
   PubMed Web of Science ®Google Scholar
• Paek KY, Hahn EJ, Son SH. Application of bioreactors for large-scale micropropagation system of plants. In Vitro Cell Dev Biol Plant. 2001;37:149–157. doi:10.1007/s11627-001-0027-9.
   Web of Science ®Google Scholar
• Kondo O, Honda H, Taya M, et al. Comparison of growth properties of carrot hairy root cultures in various bioreactors. Appl Microbiol Biotechnol. 1989;32:291–294. doi:10.1007/BF00184976.
   Web of Science ®Google Scholar
• Lehmann N, Dittler I, Lamasa M, et al. Disposable bioreactors for cultivation of plant cell cultures. Paek KY, Murthy HN, Zhong JJ, editors. Production of biomass and bioactive compounds using bioreactor technology. Dordrecht (The Netherlands): Springer Science Business Media; 2014; p. 17–46.
   Google Scholar
• Shiue A, Chen S-C, Jeng J-C, et al. Mixing performance analysis of orbitally shaken bioreactors. Appl Sci. 2020;10:5597. doi:10.3390/app10165597.
   Google Scholar
• Palazon J, Mallol A, Eibl R, et al. Growth and ginsenoside production in hairy root cultures of Panax ginseng using a novel bioreactor. Planta Med. 2003;69:344–349. doi:10.1055/s-2003-38873.
   PubMed Web of Science ®Google Scholar
• Weathers P, Wyslouzil B, Whipple M. Laboratory-scale studies of nutrient mist reactors for culturing hairy roots. Doran P, editor. Hairy roots: culture and applications. Amsterdam (Germany): Harwood Academic Publishers; 1997; p. 191–200.
   Google Scholar
• Srivastava S, Srivastava AK. In vitro azadirachtin production by hairy root cultivation of Azadirachta indica in nutrient mist bioreactor. Appl Biochem Biotechnol. 2012;166:365–378. doi:10.1007/s12010-011-9430-9.
   PubMed Web of Science ®Google Scholar
• Dilorio AA, Cheetham RD, Weathers PJ. Growth of transformed roots in a nutrient mist bioreactor: reactor performance and evaluation. Appl Microbiol Biotechnol. 1992;37:457–467. doi:10.1007/BF00180968.
   Web of Science ®Google Scholar
• Liu CZ, Wang YC, Zhao B, et al. Development of a nutrient mist bioreactor for growth of hairy roots. In Vitro Cell Dev Biol Plant. 1999;35:271–274. doi:10.1007/s11627-999-0091-0.
   Web of Science ®Google Scholar
• Williams GRC, Doran PM. Hairy root culture in a liquid-dispersed bioreactor: characterization of spatial heterogeneity. Biotechnol Prog. 2000;16:391–401. doi:10.1021/bp0000306.
   PubMed Web of Science ®Google Scholar
• Chatterjee C, Correll MJ, Weathers PJ, et al. Simplified acoustic window mist bioreactor. Biotechnol Tech. 1997;11:155–158. doi:10.1023/A:1018445228642.
   Google Scholar
• Tscheschke B, Dreimann J, von der Ruhr JW, et al. Evaluation of a new mist-chamber bioreactor for biotechnological applications. Biotechnol Bioeng. 2015;112:1155–1164. doi:10.1002/bit.25523.
   PubMed Web of Science ®Google Scholar
• Whitney P. Novel bioreactors for the growth of roots transformed by Agrobacterium rhizogenes. Enzyme Microbiol Technol. 1992;14:13–17. doi:10.1016/0141-0229(92)90019-K.
   Web of Science ®Google Scholar
• Takayama S, Misawa M. Mass propagation of Begonia x hiemalis plantlets by shake culture. Plant Cell Physiol. 1981;22:461–467.
   Web of Science ®Google Scholar
• Carlo AD, Tarraf W, Lambardi M, et al. Temporary immersion system for production of biomass and bioactive compounds from medicinal plants. Agronomy. 2021;11:2414. doi:10.3390/agronomy11122414.
   Google Scholar
• Misic D, Siler B, Skoric M, et al. Secoiridoid glycosides production by Centaurium maritimum (L.) Fritch hairy root cultures in temporary immersion bioreactors. Process Biochem. 2013;48:1587–1591. doi:10.1016/j.procbio.2013.07.015.
   Web of Science ®Google Scholar
• Vinterhalter B, Banjac N, Vinterhalter D, et al. Xanthones production in Gentiana dinariaca Beck hairy root cultures grown in simple bioreactors. Plants. 2021;10:1610. doi:10.3390/plants10081610.
   Google Scholar
• Kim YS, Hahn EJ, Paek KY. Effect of various bioreactors on growth and ginsenoside accumulation in ginseng adventitious root cultures (Panax ginseng C.A. Meyer). Korean J Plant Biotechnol. 2004;31:249–253.
   Google Scholar
• Kim YS, Hahn EJ, Shin CG, et al. Effect of aeration rate and sparger type on growth and ginsenoside accumulation in bioreactor cultures of ginseng adventitious root (Panax ginseng C.A. Meyer). Korean J Plant Biotechnol. 2005;2005;32:111–116.
   Google Scholar
• Jeong C-S, Chakrabarty D, Hahn E-J, et al. Effects of oxygen, carbon dioxide and ethylene on growth and bioactive compound production in bioreactor culture of ginseng adventitious roots. Biochem Eng J. 2006;27:252–263. doi:10.1016/j.bej.2005.08.025.
   Web of Science ®Google Scholar
• Yu KW, Hahn EJ, Paek KY. Production of adventitious ginseng roots using bioreactors. Korean J Plant Tissue Cult. 2000;27:309–315.
   Google Scholar
• Wu SQ, Lian ML, Gao R, et al. Bioreactor application on adventitious root culture of Astragalus mebranaceus. In Vitro Cell Dev Biol Plant. 2011;47:719–724. doi:10.1007/s11627-011-9376-1.
   Web of Science ®Google Scholar
• Jin H, Yu Y, Quan X, et al. Promising strategy for improving calycosin-7-O-β-D-glucoside production in Astragalus membranaceus adventitious root cultures. Ind Crops Prod. 2019;141:111792. doi:10.1016/j.indcrop.2019.111792.
   Web of Science ®Google Scholar
• Wu CH, Murthy HN, Hahn EJ, et al. Improved production of caffeic acid derivatives in suspension cultures of Echinacea purpurea by medium replenishment strategy. Arch Pharm Res. 2007;30:945–949. doi:10.1007/BF02993961.
   PubMed Web of Science ®Google Scholar
• Jeong JA, Wu CH, Murthy HN, et al. Application of an airlift bioreactor system for the production of adventitious root biomass and caffeic acid derivatives of Echinacea purpurea. Biotechnol Bioproc E. 2009;14:91–98. doi:10.1007/s12257-007-0142-5.
   Web of Science ®Google Scholar
• Gao Y, Wu CH, Piao XC, et al. Optimization of culture medium components and culture period for production of adventitious roots of Echinacea pallida (Nutt.) Nutt. Plant Cell Tiss Organ Cult. 2018;135:299–307. doi:10.1007/s11240-018-1464-z.
   Web of Science ®Google Scholar
• Lee EJ, Paek KY. Enhanced productivity of biomass and bioactive compounds through bioreactor cultures of Eleutherococcus koreanum Nakai adventitious roots affected by medium salt strength. Ind Crops Prod. 2012;36:460–465. doi:10.1016/j.indcrop.2011.10.033.
   Web of Science ®Google Scholar
• Lulu T, Park SY, Ibrahim R, et al. Production of biomass and bioactive compounds from adventitious roots by optimization of culturing conditions of Eurycoma longifolia in balloon-type bubble bioreactor system. J Biosci Bioeng. 2015;119:712–717. doi:10.1016/j.jbiosc.2014.11.010.
   PubMed Web of Science ®Google Scholar
• Cui XH, Murthy HN, Zhang JD, et al. Effect of nutritional factors on the accretion of secondary metabolites in Malaysian ginseng adventitious root cultures. Plant Biotechnol Rep. 2020;14:381–386. doi:10.1007/s11816-019-00592-7.
   Web of Science ®Google Scholar
• Fan MZ, An XL, Cui XH, et al. Production of eurycomanone and polysaccharides through adventitious root culture of Eurycoma longifolia in a bioreactor. Biochem Eng J. 2021;171:108013. doi:10.1016/j.bej.2021.108013.
   Web of Science ®Google Scholar
• Li J, Wang J, Li J, et al. Salicylic acid induces the change in the adventitious root of Glycyrrhiza uralensis Fisch.: bioactive compounds and antioxidant enzymes. Res Chem Intermed. 2016;42:1503–1519. doi:10.1007/s11164-015-2099-x.
   Web of Science ®Google Scholar
• Cui XH, Murthy HN, Jin YX, et al. Production of adventitious root biomass and secondary metabolites of Hypericum perforatum L. in a balloon-type airlift reactor. Bioresour Technol. 2011;102:10072–10079. doi:10.1016/j.biortech.2011.08.044.
   PubMed Web of Science ®Google Scholar
• Baque MA, Shiragi MHK, Moh SH, et al. Production of biomass and bioactive compounds by adventitious root suspension cultures of Morinda citrifolia (L.) in a liquid-phase airlift balloon-type bioreactor. In Vitro Cell.Dev.Biol.-Plant. 2013;49:737–749. doi:10.1007/s11627-013-9555-3.
   Web of Science ®Google Scholar
• Karatas I. Production of rosmarinic acid and biomass from adventitious root cultures of Ocimum basilicum by optimization of medium components in airlift bioreactors. Plant Cell Tissue Organ Cult. 2022;151:235–251.
   Web of Science ®Google Scholar
• Yu KW, Gao W, Hahn EJ, et al. Jasmonic acid improves ginsenoside accumulation in adventitious root culture of Panax ginseng C.A. Meyer. Biochem Eng J. 2002;11:211–215. doi:10.1016/S1369-703X(02)00029-3.
   Web of Science ®Google Scholar
• Kim YS, Hahn EJ, Murthy HN, et al. Adventitious root growth and ginsenoside accumulation in Panax ginseng cultures as affected by methyl jasmonate. Biotechnol Lett. 2004;26:1619–1622. doi:10.1007/s10529-004-3183-2.
   PubMed Web of Science ®Google Scholar
• Ho TT, Lee JD, Jeong CS, et al. Improvement of biosynthesis and accumulation of bioactive compounds by elicitation in adventitious root cultures of Polygonum multiflorum. Appl Microbiol Biotechnol. 2018;102:199–209. doi:10.1007/s00253-017-8629-2.
   PubMed Web of Science ®Google Scholar
• Rahmat E, Okello D, Kim H, et al. Scale-up production of Rehmannia glutinosa adventitious root biomass in bioreactors and improvement of its acteoside content by elicitation. Ind Crops Prod. 2021;172:114059. doi:10.1016/j.indcrop.2021.114059.
   Web of Science ®Google Scholar
• Wu CH, Murthy HN, Hahn EJ, et al. Large-scale cultivation of adventitious roots of Echinacea purpurea in airlift bioreactors for the production of chichoric acid, chlorogenic acid, and caftaric acid. Biotechnol Lett. 2007;29:1179–1182. doi:10.1007/s10529-007-9399-1.
   PubMed Web of Science ®Google Scholar
• Cui XH, Murthy HN, Paek KY. Pilot-scale culture of Hypericum perforatum L. adventitious roots in airlift bioreactors for the production of bioactive compounds. Appl Biochem Biotechnol. 2014;174:784–792. doi:10.1007/s12010-014-1123-8.
   PubMed Web of Science ®Google Scholar
• Cui HY, Baque MA, Lee EJ, et al. Scale-up of adventitious root cultures of Echinacea angustifolia in a pilot-scale bioreactor for the production of biomass and caffeic acid derivatives. Plant Biotechnol Rep. 2013;7:297–308. doi:10.1007/s11816-012-0263-y.
   Web of Science ®Google Scholar
• Kim S-J, Murthy HN, Hahn E-J, et al. Parameters affecting the extraction of ginsenosides from the adventitious roots of ginseng (Panax ginseng C.A. Meyer). Sep Purif Technol. 2007;56:401–406. doi:10.1016/j.seppur.2007.06.014.
   Web of Science ®Google Scholar
• Kim SJ, Murthy HN, Hahn EJ, et al. Effect of processing methods on the concentration of bioactive components of ginseng (Panax ginseng C.A. Meyer) adventitious roots. LWT Food Sci Technol. 2008;41:959–964. doi:10.1016/j.lwt.2007.06.012.
   Web of Science ®Google Scholar
• Sivakumar G, Yu KW, Lee JS, et al. Tissue cultured mountain ginseng adventitious rootsTM: safety and toxicology evaluation. Eng Life Sci. 2006;6:372–383. doi:10.1002/elsc.200520139.
   Web of Science ®Google Scholar
• Murthy HN, Park SY, Cui YY, et al. Food ingredients from plant cell and organ cultures: biosafety and efficacy evaluations. Paek KY, Murthy HN, Zhong JJ, editors. Production of biomass and bioactive compounds using bioreactor technology. Dordrecht (The Netherlands), Springer; 2014a; p. 251–284.
   Google Scholar
• Ali MB, Hahn EJ, Paek KY. Protective role of Panax ginseng extract on lipid peroxidation and antioxidant status in polyethylene glycol induced Spathiphyllum leaves. Biochem Eng J. 2006;32:143–148. doi:10.1016/j.bej.2006.09.013.
   Web of Science ®Google Scholar
• Lim HK, Kim YW, Lee DH, et al. The antifibrotic and antioxidant activities of hot water extract of adventitious root culture of Panax ginseng (ARCP). J Appl Biol Chem. 2007;50:74–84.
   Google Scholar
• Murthy HN, Dandin VS, Lee EJ, et al. Efficacy of ginseng adventitious root extract on hyperglycemia in streptozotocin-induced diabetic rats. J Ethnopharmacol. 2014;153:917–921. doi:10.1016/j.jep.2014.03.062.
   PubMed Web of Science ®Google Scholar
• Hong MH, Lim HK, Park JE, et al. The antihypertensive and vasodilating effects of adventitious root extracts of wild ginseng. J Korean Soc Appl Biol Chem. 2008;51:102–107.
   Google Scholar
• Yu GJ, Choi IW, Kim GY, et al. Anti-inflammatory potential of saponins derived from cultured wild ginseng root in lipopolysaccharide-stimulated RAW 264.7 macrophages. Int J Mol Med. 2015;35:1690–1698.
   PubMed Web of Science ®Google Scholar
• Lee IS, Kim SK, Jeon MH, et al. Ethyl acetate extract from tissue-cultured mountain ginseng adventitious roots inhibits in vitro platelet aggregation in whole human blood and augments peripheral blood flow in mice. J Ginseng Res. 2011;35:442–448. doi:10.5142/jgr.2011.35.4.442.
   PubMed Web of Science ®Google Scholar
• Murthy HN, Dandin VS, Paek KY. Hepatoprotective activity of ginsenosides from Panax ginseng adventitious roots against carbon tetrachloride treated hepatic injury in rats. J Ethnopharmacol. 2014;158:442–446. doi:10.1016/j.jep.2014.10.047.
   PubMed Web of Science ®Google Scholar
• Oh CH, Kang PS, Kim JW, et al. Water extracts of cultured mountain ginseng stimulate immune cells and inhibit cancer cell proliferation. Food Sci Biotechnol. 2006;15:369–373.
   Web of Science ®Google Scholar
• Lee EJ, Zhao HL, Li DW, et al. Effect of MeOH extract adventitious root culture of Panax ginseng on hyperlipidemic rat induced by high fat-rich diet. Korean J Pharmcogn. 2003;34:179–184.
   Google Scholar
• Park JS, Hwang SY, Lee WS, et al. The therapeutic effect of tissue cultured root of wild Panax ginseng C.A. Meyer on spermatogenic disorder. Arch Pharm Res. 2006;29:800–807. doi:10.1007/BF02974082.
   PubMed Web of Science ®Google Scholar
• Murthy HN, Georgiev MI, Park SY, et al. The safety assessment of food ingredients derived from plant cell, tissue and organ cultures: a review. Food Chem. 2015;176:426–432. doi:10.1016/j.foodchem.2014.12.075.
   PubMed Web of Science ®Google Scholar
• Gubser G, Vollenweider S, Eibl D, et al. Food ingredients and food made with plant cell and tissue cultures: state-of-the-art and future trends. Eng Life Sci. 2021;21:87–98. doi:10.1002/elsc.202000077.
   PubMed Web of Science ®Google Scholar
• Baek S, Han JE, Ho TT, et al. Development of hairy root cultures for biomass and triterpenoid production in Centella asiatica. Plants. 2022;11:148. doi:10.3390/plants11020148.
   Google Scholar
• Ho TT, Murthy HN, Dalawai D, et al. Attributes of Polygonum multiflorum to transfigure red biotechnology. Appl Microbiol Biotechnol. 2019;103:3317–3326. doi:10.1007/s00253-019-09709-y.
   PubMed Web of Science ®Google Scholar
• Ho TT, Lee KJ, Lee JD, et al. Adventitious root culture of Polygonum multiflorum for phenolic compounds and its pilot-scale production in 500 L-tank. Plant Cell Tiss Organ Cult. 2017;130:167–181. doi:10.1007/s11240-017-1212-9.
   Web of Science ®Google Scholar