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Bacterial endophytes from ginseng and their biotechnological application

  • Chu, Luan Luong (Faculty of Biotechnology, Chemistry and Environmental Engineering, Phenikaa University) ;
  • Bae, Hanhong (Department of Biotechnology, Yeungnam University)
  • Received : 2020.09.01
  • Accepted : 2021.04.09
  • Published : 2022.01.01

Abstract

Ginseng has been well-known as a medicinal plant for thousands of years. Bacterial endophytes ubiquitously colonize the inside tissues of ginseng without any disease symptoms. The identification of bacterial endophytes is conducted through either the internal transcribed spacer region combined with ribosomal sequences or metagenomics. Bacterial endophyte communities differ in their diversity and composition profile, depending on the geographical location, cultivation condition, and tissue, age, and species of ginseng. Bacterial endophytes have a significant effect on the growth of ginseng through indole-3-acetic acid (IAA) and siderophore production, phosphate solubilization, and nitrogen fixation. Moreover, bacterial endophytes can protect ginseng by acting as biocontrol agents. Interestingly, bacterial endophytes isolated from Panax species have the potential to produce ginsenosides and bioactive metabolites, which can be used in the production of food and medicine. The ability of bacterial endophytes to transform major ginsenosides into minor ginsenosides using β-glucosidase is gaining increasing attention as a promising biotechnology. Recently, metabolic engineering has accelerated the possibilities for potential applications of bacterial endophytes in producing beneficial secondary metabolites.

Keywords

Acknowledgement

This study was carried out with the support of the Forest Science and Technology project (Project No. 2019147B10-2121-AB02) provided by Korea Forest Service.

References

  1. Li CP, Li RC. An introductory note to ginseng. Am J Chin Med (Gard City N Y). 1973;1:249-61. https://doi.org/10.1142/S0192415X73000279
  2. Boopathi V, Subramaniyam S, Mathiyalagan R, Yang DC. Till 2018: a survey of biomolecular sequences in genus Panax. J Ginseng Res 2020;44(1):33-43. https://doi.org/10.1016/j.jgr.2019.06.004
  3. Kim DH. Chemical diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res 2012;36(1):1-15. https://doi.org/10.5142/jgr.2012.36.1.1
  4. Lee SM, Bae BS, Park HW, Ahn NG, Cho BG, Cho YL, et al. Characterization of Korean red ginseng (Panax ginseng Meyer): history, preparation method, and chemical composition. J Ginseng Res 2015;39(4):384-91. https://doi.org/10.1016/j.jgr.2015.04.009
  5. Yang W, Qiao X, Li K, Fan J, Bo T, Guo DA, et al. Identification and differentiation of Panax ginseng, Panax quinquefolium, and Panax notoginseng by monitoring multiple diagnostic chemical markers. Acta Pharm Sin B 2016;6(6):568-75. https://doi.org/10.1016/j.apsb.2016.05.005
  6. Kim K, Nguyen VB, Dong J, Wang Y, Park JY, Lee CL, et al. Evolution of the Araliaceae family inferred from complete chloroplast genomes and 45S nrDNAs of 10 Panax-related species. Sci Rep 2017;7:4917. https://doi.org/10.1038/s41598-017-05218-y
  7. Baeg IH, So SH. The world ginseng market and the ginseng (Korea). J Ginseng Res 2013;37(1):1-7. https://doi.org/10.5142/jgr.2013.37.1
  8. Riaz M, Rahman NU, Zia-Ul-Haq M, Jaffar HZE, Manea R. Ginseng: a dietary supplement as immune-modulator in various diseases. Trends Food Sci Technol 2019;83:12-30. https://doi.org/10.1016/j.tifs.2018.11.008
  9. Future Market Insights. Ginseng market: 2019 analysis and review citrus flavours market by source-wild and cultivated for 2019-2027 [Internet]. 2020 Feb 27. https://www.futuremarketinsights.com/reports/ginsengmarket.
  10. Proctor JT, Sullivan AJ, Rupasinghe VP, Jackson CJ. Morphological and ginsenoside differences among North American ginseng leaves. J Ginseng Res 2011;35(2):155-61. https://doi.org/10.5142/jgr.2011.35.2.161
  11. Kim YJ, Zhang D, Yang DC. Biosynthesis and biotechnological production of ginsenosides. Biotechnol Adv 2015;33(6 Pt 1):717-35. https://doi.org/10.1016/j.biotechadv.2015.03.001
  12. Cho CW, Kim YC, Kang JH, Rhee YK, Choi SY, Kim KT, et al. Characteristic study on the chemical components of Korean curved ginseng products. J Ginseng Res 2013;37(3):349-54. https://doi.org/10.5142/jgr.2013.37.349
  13. Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 2015;39(4):287-98. https://doi.org/10.1016/j.jgr.2014.12.005
  14. Chu LL, Montecillo J, Bae H. Recent advances in the metabolic engineering of yeasts for ginsenoside biosynthesis. Front Bioeng Biotechnol 2020;8:139. https://doi.org/10.3389/fbioe.2020.00139
  15. Biswas T, Mathur AK, Mathur A. A literature update elucidating production of Panax ginsenosides with a special focus on strategies enriching the antineoplastic minor ginsenosides in ginseng preparations. Appl Microbiol Biotechnol 2017;101(10):4009-32. https://doi.org/10.1007/s00253-017-8279-4
  16. Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee JS, et al. Pharmacological potential of ginseng and its major component ginsenosides. J Ginseng Res 2020. https://doi.org/10.1016/j.jgr.2020.02.004.
  17. Kang S, Min H. Ginseng, the 'Immunity Boost': the effects of Panax ginseng on immune system. J Ginseng Res 2012;36(4):354-68. https://doi.org/10.5142/jgr.2012.36.4.354
  18. Bai L, Gao J, Wei F, Zhao J, Wang D, Wei J. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Front Pharmacol 2018;9:423. https://doi.org/10.3389/fphar.2018.00423
  19. Kim JH. Pharmacological and medical applications of Panax ginseng and ginsenosides: a review for use in cardiovascular diseases. J Ginseng Res 2018;42(3):264-9. https://doi.org/10.1016/j.jgr.2017.10.004
  20. Ong WY, Farooqui T, Koh HL, Farooqui AA, Ling EA. Protective effects of ginseng on neurological disorders. Front Aging Neurosci 2015;7:129.
  21. Wang L, Yang X, Yu X, Yao Y, Ren G. Evaluation of antibacterial and anti-inflammatory activities of less polar ginsenosides produced from polar ginsenosides by heat-transformation. J Agric Food Chem 2013;61(50):12274-82. https://doi.org/10.1021/jf404461q
  22. Dong W, Farooqui A, Leon AJ, Kelvin DJ. Inhibition of influenza A virus infection by ginsenosides. PLoS One 2017;12(2):e0171936. https://doi.org/10.1371/journal.pone.0171936
  23. Leung KW, Wong AS. Ginseng and male reproductive function. Spermatogenesis 2013;3(3):e26391. https://doi.org/10.4161/spmg.26391
  24. Chen J, Du B, Cai W, Xu B. Ginsenosides and amino acids in flavored ginseng chips as affected by food formulation and processing technology. Lwt-Food Sci Technol 2015;62(1):517-24. https://doi.org/10.1016/j.lwt.2014.10.047
  25. Kim E, Kim D, Yoo S, Hong YH, Han SY, Jeong S, et al. The skin protective effects of compound K, a metabolite of ginsenoside Rb1 from Panax ginseng. J Ginseng Res 2018;42(2):218224.
  26. Ryan RP, Germaine K, Franks A, Ryan DJ, Dowling DN. Bacterial endophytes: recent developments and applications. FEMS Microbiol Lett 2008;278(1):1-9. https://doi.org/10.1111/j.1574-6968.2007.00918.x
  27. Kusari S, Hertweck C, Spiteller M. Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 2012;19(7):792-8. https://doi.org/10.1016/j.chembiol.2012.06.004
  28. Golinska P, Wypij M, Agarkar G, Rathod D, Dahm H, Rai M. Endophytic actinobacteria of medicinal plants: diversity and bioactivity. Antonie Van Leeuwenhoek 2015;108(2):267-89. https://doi.org/10.1007/s10482-015-0502-7
  29. Nalini MS, Prakash HS. Diversity and bioprospecting of actinomycete endophytes from the medicinal plants. Lett Appl Microbiol 2017;64(4):261-70. https://doi.org/10.1111/lam.12718
  30. Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, et al. Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 2015;33(8):1582-614. https://doi.org/10.1016/j.biotechadv.2015.08.001
  31. Gouda S, Das G, Sen SK, Shin HS, Patra JK. Endophytes: a treasure house of bioactive compounds of medicinal importance. Front Microbiol 2016;7:1538. https://doi.org/10.3389/fmicb.2016.01538
  32. Hyde KD, Bussaban B, Paulus B, Crous PW, Lee S, Mckenzie EHC, et al. Diversity of saprobic microfungi. Biodivers Conserv 2007;16:7-35. https://doi.org/10.1007/s10531-006-9119-5
  33. Park YH, Kim Y, Mishra RC, Bae H. Fungal endophytes inhabiting mountain-cultivated ginseng (Panax ginseng Meyer): diversity and biocontrol activity against ginseng pathogens. Sci Rep 2017;7(1):16221. https://doi.org/10.1038/s41598-017-16181-z
  34. Chowdhury MDEK, Jeon J, Rim SO, Park Y-H, Lee SK, Bae H. Composition, diversity and bioactivity of culturable bacterial endophytes in mountain-cultivated ginseng in Korea. Sci Rep 2017;7(1):10098. https://doi.org/10.1038/s41598-017-10280-7
  35. Cho KM, Hong SY, Lee SM, Kim YH, Kahng GG, Lim YP, et al. Endophytic bacterial communities in ginseng and their antifungal activity against pathogens. Microb Ecol 2007;54(2):341-51. https://doi.org/10.1007/s00248-007-9208-3
  36. Hong CE, Kim JU, Lee JW, Bang KH, Jo IH. Metagenomic analysis of bacterial endophyte community structure and functions in Panax ginseng at different ages. 3 Biotech 2019;9(8):300. https://doi.org/10.1007/s13205-019-1838-x
  37. Guan Y, Chen M, Ma Y, Du Z, Yuan N, Li Y, Xiao J, Zhang Y. Whole-genome and time-course dual RNA-Seq analyses reveal chronic pathogenicity-related gene dynamics in the ginseng rusty root rot pathogen Ilyonectria robusta. Sci Rep 2020;10(1):17122. https://doi.org/10.1038/s41598-020-73761-2
  38. Fu Y, Yin ZH, Yin CY. Biotransformation of ginsenoside Rb1 to ginsenoside Rg3 by endophytic bacterium Burkholderia sp. GE 17-7 isolated from Panax ginseng. J Appl Microbiol 2017;122(6):1579-85. https://doi.org/10.1111/jam.13435
  39. Fu Y. Biotransformation of ginsenoside Rb1 to Gyp-XVII and minor ginsenoside Rg3 by endophytic bacterium Flavobacterium sp. GE 32 isolated from Panax ginseng. Lett Appl Microbiol 2019;68(2):134-41. https://doi.org/10.1111/lam.13090
  40. Fu Y, Yin ZH, Wu LP, Yin CR. Biotransformation of ginsenoside Rb1 to ginsenoside C-K by endophytic fungus Arthrinium sp. GE 17-18 isolated from Panax ginseng. Lett Appl Microbiol 2016;63(3):196-201. https://doi.org/10.1111/lam.12606
  41. Shi J, Zeng Q, Liu Y, Pan Z. Alternaria sp. MG1, a resveratrol-producing fungus: isolation, identification, and optimal cultivation conditions for resveratrol production. Appl Microbiol Biotechnol 2012;95(2):369-79. https://doi.org/10.1007/s00253-012-4045-9
  42. Park YH, Mishra RC, Yoon S, Kim H, Park C, Seo ST, et al. Endophytic Trichoderma citrinoviride isolated from mountain-cultivated ginseng (Panax ginseng) has great potential as a biocontrol agent against ginseng pathogens. J Ginseng Res 2019;43(3):408-20. https://doi.org/10.1016/j.jgr.2018.03.002
  43. Subramanian M, Marudhamuthu M. Hitherto unknown terpene synthase organization in Taxol-producing endophytic bacteria isolated from marine macroalgae. Curr Microbiol 2020;77(6):918-23. https://doi.org/10.1007/s00284-020-01878-8
  44. Ma L, Cao YH, Cheng MH, Huang Y, Mo MH, Wang Y, et al. Phylogenetic diversity of bacterial endophytes of Panax notoginseng with antagonistic characteristics towards pathogens of root-rot disease complex. Antonie Van Leeuwenhoek 2013;103(2):299-312. https://doi.org/10.1007/s10482-012-9810-3
  45. Dong L, Cheng R, Xiao L, Wei F, Wei G, Xu J, et al. Diversity and composition of bacterial endophytes among plant parts of Panax notoginseng. Chin Med 2018;13:41. 2018. https://doi.org/10.1186/s13020-018-0198-5
  46. Eevers N, Gielen M, Sanchez-Lopez A, Jaspers S, White JC, Vangronsveld J, et al. Optimization of isolation and cultivation of bacterial endophytes through addition of plant extract to nutrient media. Microb Biotechnol 2015;8(4):707-15. https://doi.org/10.1111/1751-7915.12291
  47. Song X, Wu H, Yin Z, Lian M, Yin C. Endophytic bacteria isolated from Panax ginseng improves ginsenoside accumulation in adventitious ginseng root culture. Molecules 2017;22(6):837. https://doi.org/10.3390/molecules22060837
  48. Singh D, Sharma A, Saini GK. Biochemical and molecular characterisation of the bacterial endophytes from native sugarcane varieties of Himalayan region. 3 Biotech 2013;3(3):205-12. https://doi.org/10.1007/s13205-012-0084-2
  49. Tam NT, Tam NP, Nguyen VTH, Hung NK, Huy CN, Ngoc PB, et al. Isolation and screening of endophytic bacteria from Ngoc Linh ginseng (Panax vietnamensis Ha et Grushv) for biosynthesis b-glucosidase. J Bio 2018;40(2):154-62. 15625/0866-7160/v40n2.10862.
  50. Poretsky R, Rodriguez -RLM, Luo C, Tsementzi D, Konstantinidis KT. Strengths and limitations of 16S rRNA gene amplicon sequencing in revealing temporal microbial community dynamics. PLoS One 2014;9(4):e93827. https://doi.org/10.1371/journal.pone.0093827
  51. Liu S, Li D, Cui X, Chen L, Nian H. Community analysis of endophytic bacteria from the seeds of the medicinal plant Panax notoginseng. J Agric Sci 2017;9(1).
  52. Fadiji AE, Babalola OO. Elucidating mechanisms of endophytes used in plant protection and other bioactivities with multifunctional prospects. Front Bioeng Biotechnol 2020;8:467. https://doi.org/10.3389/fbioe.2020.00467
  53. Kim H, Mohanta TK, Park YH, Park SC, Shanmugam G, Park JS, et al. Complete genome sequence of the mountain-cultivated ginseng endophyte Burkholderia stabilis and its antimicrobial compounds against ginseng root rot disease. Biol Control 2020;140:104126. https://doi.org/10.1016/j.biocontrol.2019.104126
  54. Tan Y, Cui Y, Li H, Kuang A, Li X, Wei Y, et al. Diversity and composition of rhizospheric soil and root endogenous bacteria in Panax notoginseng during continuous cropping practices. J Basic Microbiol 2017;57(4):337-44. https://doi.org/10.1002/jobm.201600464
  55. Liu X, Zhao Z, Li S, Zhang L, Tian Y, Sun F. The community structure and diversity of the endophytes in American ginseng. Wei Sheng Wu Xue Bao 2015;55(3):330-40.
  56. Hong CE, Kim JU, Lee JW, Lee SW, Jo IH. Diversity of bacterial endophytes in Panax ginseng and their protective effects against pathogens. 3 Biotech 2018;8(9):397. https://doi.org/10.1007/s13205-018-1417-6
  57. Chi F, Shen SH, Cheng HP, Jing YX, Yanni YG, Dazzo FB. Ascending migration of endophytic rhizobia, from roots to leaves, inside rice plants and assessment of benefits to rice growth physiology. Appl Environ Microbiol 2005;71(11):7271-8. https://doi.org/10.1128/AEM.71.11.7271-7278.2005
  58. Park YH, Lee SG, Ahn DJ, Kwon TR, Park SU, Lim HS, et al. Diversity of fungal endophytes in various tissues of Panax ginseng Meyer cultivated in Korea. J Ginseng Res 2012;36(2):211-7. https://doi.org/10.5142/jgr.2012.36.2.211
  59. Vendan RT, Yu YJ, Lee SH, Rhee YH. Diversity of endophytic bacteria in ginseng and their potential for plant growth promotion. J Microbiol 2010;48(5):559-65. https://doi.org/10.1007/s12275-010-0082-1
  60. Zhang H, Abid S, Ahn JC, Mathiyalagan R, Kim YJ, Yang DC, Wang Y. Characteristics of Panax ginseng cultivars in Korea and China. Molecules 2020;25(11):2635. https://doi.org/10.3390/molecules25112635
  61. Wang S, Ren X, Huang B, Wang G, Zhou P, An Y. Aluminium-induced reduction of plant growth in alfalfa (Medicago sativa) is mediated by interrupting auxin transport and accumulation in roots. Sci Rep 2016;6:30079. https://doi.org/10.1038/srep30079
  62. Spaepen S, Vanderleyden J. Auxin and plant-microbe interactions. Cold Spring Harb Perspect Biol 2011;3(4):a001438. https://doi.org/10.1101/cshperspect.a001438
  63. Um Y, Kim BR, Jeong JJ, Chung CM, Lee Y. Identification of endophytic bacteria in Panax ginseng seeds and their potential for plant growth promotion. Korean J Med Crop Sci 2014;22(4):306-12. https://doi.org/10.7783/KJMCS.2014.22.4.306
  64. Gao Y, Liu Q, Zang P, Li X, Ji Q, He Z, Zhao Y, Yang H, Zhao X, Zhang L. An endophytic bacterium isolated from Panax ginseng C.A. Meyer enhances growth, reduces morbidity, and stimulates ginsenoside biosynthesis. Phytochem Lett 2015;11:132-8. https://doi.org/10.1016/j.phytol.2014.12.007
  65. Leventhal GE, Ackermann M, Schiessl KT. Why microbes secrete molecules to modify their environment: the case of iron-chelating siderophores. J R Soc Interface 2019;16(150):20180674. https://doi.org/10.1098/rsif.2018.0674
  66. Ferreira CMH, Vilas-Boas A, Sousa CA, Soares HMVM, Soares EV. Comparison of five bacterial strains producing siderophores with ability to chelate iron under alkaline conditions. AMB Express 2019;9(1):78. https://doi.org/10.1186/s13568-019-0796-3
  67. Rungin S, Indananda C, Suttiviriya P, Kruasuwan W, Jaemsaeng R, Thamchaipenet A. Plant growth enhancing effects by a siderophore-producing endophytic streptomycete isolated from a Thai jasmine rice plant (Oryza sativa L. cv. KDML105). Antonie Van Leeuwenhoek 2012;102(3):463-72. https://doi.org/10.1007/s10482-012-9778-z
  68. Sharma SB, Sayyed RZ, Trivedi MH, Gobi TA. Phosphate solubilizing microbes: sustainable approach for managing phosphorus deficiency in agricultural soils. SpringerPlus 2013;2:587. https://doi.org/10.1186/2193-1801-2-587
  69. Yang Z, Yang S, Van Nostrand JD, Zhou J, Fang W, Qi Q, et al. Microbial community and functional gene changes in arctic tundra soils in a microcosm warming experiment. Front Microbiol 2017;8:1741. https://doi.org/10.3389/fmicb.2017.01741
  70. Wang J, Li R, Zhang H, Wei G, Li Z. Beneficial bacteria activate nutrients and promote wheat growth under conditions of reduced fertilizer application. BMC Microbiol 2020;20(1):38. https://doi.org/10.1186/s12866-020-1708-z
  71. Suzuki I, Horie N, Sugiyama T, Omata T. Identification and characterization of two nitrogen-regulated genes of the cyanobacterium Synechococcus sp. strain PCC7942 required for maximum efficiency of nitrogen assimilation. J Bacteriol 1995;177(2):290-6. https://doi.org/10.1128/jb.177.2.290-296.1995
  72. Herrero A, Muro-Pastor AM, Flores E. Nitrogen control in cyanobacteria. J Bacteriol 2001;183(2):411-25. https://doi.org/10.1128/JB.183.2.411-425.2001
  73. Yurgel SN, Rice J, Mulder M, Kahn ML. GlnB/GlnK PII proteins and regulation of the Sinorhizobium meliloti Rm1021 nitrogen stress response and symbiotic function. J Bacteriol 2010;192(10):2473-81. https://doi.org/10.1128/JB.01657-09
  74. Ek-Ramos MJ, Gomez-Flores R, Orozco-Flores AA, Rodriguez-Padilla C, Gonzalez-Ochoa G, Tamez-Guerra P. Bioactive products from plant-endophytic gram-positive bacteria. Front. Microbiol 2019;10:463. https://doi.org/10.3389/fmicb.2019.00463
  75. Yu H, Zhao J, You J, Li J, Ma H, Chen X. Factors influencing cultivated ginseng (Panax ginseng C. A. Meyer) bioactive compounds. PLoS One 2019;14(10):e0223763. https://doi.org/10.1371/journal.pone.0223763
  76. Fischer D, Gessner G, Fill TP, Barnett R, Tron K, Dornblut K, et al. Disruption of membrane integrity by the bacterium-derived antifungal Jagaricin. Antimicrob Agents Chemother 2019;63(9):e00707-19.
  77. Huang H, Ullah F, Zhou DX, Yi M, Zhao Y. Mechanisms of ROS regulation of plant development and stress responses. Front Plant Sci 2019;10:800. https://doi.org/10.3389/fpls.2019.00800
  78. Vannier N, Agler M, Hacquard S. Microbiota-mediated disease resistance in plants. PLoS Pathog 2019;15(6):e1007740. https://doi.org/10.1371/journal.ppat.1007740
  79. Cui JL, Wang YN, Jiao J, Gong Y, Wang JH, Wang ML. Fungal endophyte-induced salidroside and tyrosol biosynthesis combined with signal crosstalk and the mechanism of enzyme gene expression in Rhodiola crenulata. Sci Rep 2017;7(1):12540. https://doi.org/10.1038/s41598-017-12895-2
  80. Scheffers DJ, Pinho MG. Bacterial cell wall synthesis: new insights from localization studies. Microbiol Mol Biol Rev 2005;69(4):585-607. https://doi.org/10.1128/MMBR.69.4.585-607.2005
  81. Verma SC, Ladha JK, Tripathi AK. Evaluation of plant growth promoting and colonization ability of endophytic diazotrophs from deep water rice. J Biotechnol 2001;81:127-41.
  82. Suto M, Takebayashi M, Saito K, Tanaka M, Yokota A, Tomita F. Endophytes as producers of xylanase. J Biosci Bioeng 2002;93:88-90. https://doi.org/10.1016/S1389-1723(02)80059-7
  83. Chowdhury MDEK, Bae H. Bacterial endophytes isolated from mountain-cultivated ginseng (Panax ginseng Mayer) have biocontrol potential against ginseng pathogens. Biol Control 2018;126:97-108. https://doi.org/10.1016/j.biocontrol.2018.08.006
  84. Chandler D, Bailey AS, Tatchell GM, Davidson G, Greaves J, Grant WP. The development, regulation and use of biopesticides for integrated pest management. Philos Trans R Soc B 2011;366(1573):1987-98. https://doi.org/10.1098/rstb.2010.0390
  85. Llontop MME, Hurley K, Tian L, Galeano VAB, Wildschutte HK, Marine SC, et al. Exploring rain as source of biological control agents for fire blight on apple. Front Microbiol 2020;11:199. https://doi.org/10.3389/fmicb.2020.00199
  86. Pawar S, Chaudhari A, Prabha R, Shukla R, Singh DP. Microbial pyrrolnitrin: natural metabolite with immense practical utility. Biomolecules 2019;9(9):443. https://doi.org/10.3390/biom9090443
  87. Szakiel A, Paczkowski C, Henry M. Influence of environmental abiotic factors on the content of saponins in plants. Phytochem Rev 2011;10:471-91. https://doi.org/10.1007/s11101-010-9177-x
  88. Kim DS, Song M, Kim SH, Jang DS, Kim JB, Ha BK, et al. The improvement of ginsenoside accumulation in Panax ginseng as a result of 𝛾-irradiation. J Ginseng Res 2013;37(3):332-40. https://doi.org/10.5142/jgr.2013.37.332
  89. Oh JY, Kim YJ, Jang MG, Joo SC, Kwon WS, Kim SY, et al. Investigation of ginsenosides in different tissues after elicitor treatment in Panax ginseng. J Ginseng Res 2014;38(4):270-7. https://doi.org/10.1016/j.jgr.2014.04.004
  90. Ma R, Sun L, Chen X, Mei B, Chang G, Wang M, et al. Proteomic analyses provide novel insights into plant growth and ginsenoside biosynthesis in forest cultivated Panax ginseng (F. Ginseng). Front Plant Sci 2016;7:1. https://doi.org/10.3389/fpls.2016.00001
  91. Xue L, He Z, Bi X, Xu W, Wei T, Wu S, et al. Transcriptomic profiling reveals MEP pathway contributing to ginsenoside biosynthesis in Panax ginseng. BMC Genomics 2019;20(1):383. https://doi.org/10.1186/s12864-019-5718-x
  92. Lee HJ, Jeong J, Alves AC, Han ST, In G, Kim EH, et al. Metabolomic understanding of intrinsic physiology in Panax ginseng during whole growing seasons. J Ginseng Res 2019;43(4):654-65. https://doi.org/10.1016/j.jgr.2019.04.004
  93. Zhang MM, Wang Y, Ang EL, Zhao H. Engineering microbial hosts for production of bacterial natural products. Nat Prod Rep 2016;33(8):963-87. https://doi.org/10.1039/c6np00017g
  94. Chemat F, Vian MA, Fabiano-Tixier AS, Nutrizio M, Jambrak AR, Munekata PE. A review of sustainable and intensified techniques for extraction of food and natural products. Green Chem 2020;22:2325-53. https://doi.org/10.1039/c9gc03878g
  95. Hardoim PR, van Overbeek LS, Berg G, Pirttila AM, Compant S, Campisano A, et al. The hidden world within plants: ecological and evolutionary considerations for defining functioning of microbial endophytes. Microbiol Mol Biol Rev 2015;79(3):293-320. https://doi.org/10.1128/MMBR.00050-14
  96. Yue J, Hu X, Sun H, Yang Y, Huang J. Widespread impact of horizontal gene transfer on plant colonization of land. Nat Commun 2012;3:1152. https://doi.org/10.1038/ncomms2148
  97. Yan H, Jin H, Fu Y, Yin Z, Yin C. Production of rare ginsenosides Rg3 and Rh2 by endophytic bacteria from Panax ginseng. J Agric Food Chem 2019;67(31):8493-9. https://doi.org/10.1021/acs.jafc.9b03159
  98. Geraldi A. Advances in the production of minor ginsenosides using microorganisms and their enzymes. BIO Integration 2020;1(1):15-24. https://doi.org/10.15212/bioi-2020-0007
  99. Li W, Fan D. Biocatalytic strategies for the production of ginsenosides using glycosidase: current state and perspectives. Appl Microbiol Biotechnol 2020;104:3807-23. https://doi.org/10.1007/s00253-020-10455-9
  100. Hegazy ME, Mohamed TA, ElShamy AI, Mohamed AE, Mahalel UA, Reda EH, et al. Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: a review. J Adv Res 2015;6(1):17-33. https://doi.org/10.1016/j.jare.2014.11.009
  101. de Carvalho CC. Whole cell biocatalysts: essential workers from nature to the industry. Microb Biotechnol 2017;10(2):250-63. https://doi.org/10.1111/1751-7915.12363
  102. Hug JJ, Krug D, Muller R. Bacteria as genetically programmable producers of bioactive natural products. Nat Rev Chem 2020;4:172-93. https://doi.org/10.1038/s41570-020-0176-1
  103. Yu S, Zhou X, Li F, Xu C, Zheng F, Li J, et al. Microbial transformation of ginsenoside Rb1, Re and Rg1 and its contribution to the improved anti-inflammatory activity of ginseng. Sci Rep 2017;7(1):138. https://doi.org/10.1038/s41598-017-00262-0