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Recent Strategies to Engineer Alkaloid Biosynthesis in Medicinal Plants

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Medicinal Plants

Abstract

Plants are known to synthesize a plethora of secondary metabolites viz., terpenoids, terpenes, flavonoids and alkaloids. Of these, alkaloids belong to a major class of phytoconstituents, which are responsible for many properties of therapeutic interest such as analgesic, antimicrobial, antimalarial, antipyretic, antihypertensive, cardioprotective, anticancer and antiarrhythmic. Consequently, plants possess several biosynthetic pathways which are critical for alkaloid biosynthesis. The recent involvement of commercial interest has triggered the exploration of techniques for altering the production of alkaloids. Moreover, the amount of natural production of alkaloids is low and vulnerable due to the dependency on climatic conditions. Considering the above facts, different techniques such as transcription factors plant tissue culture, miRNA-mediated manipulation of these secondary metabolites, gene editing by CRISPR/Cas9, and nanoparticles (NPs)-based enhancement are being extensively used to stabilize and enhance alkaloid production for the large-scale use at the industrial level. Additionally, a detailed understanding of alkaloid biosynthetic pathway genes, transcription factors and their mode of action is essential for the improved production of important alkaloids. This chapter is focussed on reviewing a set of biotechnological tools that are the potential candidates for improved biosynthesis of different alkaloids, which can further revolutionize the pharmaceutical industry.

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References

  • Alagoz Y, Gurkok T, Zhang B, Unver T (2016) Manipulating the biosynthesis of bioactive compound alkaloids for next-generation metabolic engineering in opium poppy using CRISPR-Cas 9 genome editing technology. Sci Rep 6:30910

    Article  CAS  Google Scholar 

  • Apuya NR, Park JH, Zhang L, Ahyow M, Davidow P, Van Fleet J, Rarang JC, Hippley M, Johnson TW, Yoo HD, Trieu A, Krueger S, Wu CY, Lu YP, Flavell RB, Bobzin SC (2008) Enhancement of alkaloid production in opium and California poppy by transactivation using heterologous regulatory factors. Plant Biotechnol J 6:160–175

    Article  CAS  Google Scholar 

  • Asgari-Targhi G, Iranbakhsh A, Ardebili ZO (2018) Potential benefits and phytotoxicity of bulk and nano-chitosan on the growth, morphogenesis, physiology, and micropropagation of Capsicum annuum. Plant Physiol Biochem 127:93–102

    Article  Google Scholar 

  • Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH, Rollinger JM, Schuster D, Breuss JM, Bochkov V, Mihovilovic MD, Kopp B, Bauer R, Dirsch VM, Stuppner H (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33:582–1614

    Article  Google Scholar 

  • Atanasov AG, Zotchev SB, Dirsch VM, International Natural Product Sciences Taskforce, Supuran CT (2021) Natural products in drug discovery: advances and opportunities. Nat Rev Drug Discov 20:200–216

    Article  CAS  Google Scholar 

  • Baltes NJ, Gil-Humanes J, Cermak T, Atkins PA, Voytas DF (2014) DNA replicons for plant genome engineering. Plant Cell 26:151–163

    Article  CAS  Google Scholar 

  • Barozai MYK, Baloch IA, Din M (2012) Identification of microRNAs and their targets in Helianthus. Mol Biol Rep 39:2523–2532

    Article  CAS  Google Scholar 

  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  Google Scholar 

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Bhadra R, Vani S, Shanks JV (1993) Production of indole alkaloids by selected hairy root lines of Catharanthus roseus. Biotechnol Bioeng 41:503–602

    Article  Google Scholar 

  • Boke H, Ozhuner E, Turktas M, Parmaksiz I, Ozcan S, Unver T (2015) Regulation of the alkaloid biosynthesis by miRNA in opium poppy. Plant Biotechnol J 13:409–420

    Article  CAS  Google Scholar 

  • Caporale LH (1995) Chemical ecology: a view from the pharmaceutical industry. Proc Natl Acad Sci USA 92:75–82

    Article  CAS  Google Scholar 

  • Cárdenas PD, Sonawane PD, Pollier J, Vanden Bossche R, Dewangan V, Weithorn E, Tal L, Meir S, Rogachev I, Malitsky S, Giri AP, Goossens A, Burdman S, Aharoni A (2016) GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway. Nat Commun 7:10654

    Article  Google Scholar 

  • Chatel G, Montiel G, Pre M, Memelink J, Thiersault M, Saint-Pierre B, Doireau P, Gantet P (2003) CrMYC1, a Catharanthus roseus elicitor- and jasmonate-responsive bHLH transcription factor that binds the G-box element of the strictosidine synthase gene promoter. J Exp Bot 54:2587–2588

    Article  CAS  Google Scholar 

  • Cheirmadurai K, Biswas S, Murali R, Thanikaivelan P (2014) Green synthesis of copper nanoparticles and conducting nanobiocomposites using plant and animal sources. RSC Adv 4:19507–19511

    Article  CAS  Google Scholar 

  • Chen K, Gao C (2015) Targeted gene mutation in plants. In: Li XQ et al (eds) Somatic genome manipulation. Springer, Cham, pp 253–272

    Chapter  Google Scholar 

  • Cho SW, Kim S, Kim JM, Kim JS (2013) Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31:230–232

    Article  CAS  Google Scholar 

  • Choi KB, Morishige T, Shitan N, Yazaki K, Sato F (2002) Molecular cloning and characterization of coclaurinen-methyltransferase from cultured cells of Coptis japonica. J Biol Chem 277:830–835

    Article  CAS  Google Scholar 

  • Cushnie TP, Cushnie B, Lamb AJ (2014) Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int J Antimicrob Agents 44:377–386

    Article  CAS  Google Scholar 

  • Das P, Barua S, Sarkar S, Karak N, Bhattacharyya P, Raza N, Kim KH, Bhattacharya SS (2018) Plant extract–mediated green silver nanoparticles: efficacy as soil conditioner and plant growth promoter. J Hazard Mater 346:6272

    Article  Google Scholar 

  • Dasgupta A, Chowdhury N, De RK (2020) Metabolic pathway engineering: perspectives and applications. Comput Methods Prog Biomed 192:105436

    Article  Google Scholar 

  • Dayakar T, Rao KV, Bikshalu K, Rajendar V, Park SH (2017) Novel synthesis and characterization of pristine Cu nanoparticles for the non-enzymatic glucose biosensor. J Mater Sci Mater Med 28:109

    Article  CAS  Google Scholar 

  • De Boer K, Tilleman S, Pauwels L, Vanden Bossche R, De Sutter V, Vanderhaeghen R, Hilson P, Hamill JD, Goossens A (2011) APETALA2/ETHYLENE RESPONSE FACTOR and basic helix-loop-helix tobacco transcription factors cooperatively mediate jasmonate-elicited nicotine biosynthesis. Plant J 66:1053–1065

    Article  Google Scholar 

  • De Sutter V, Vanderhaeghen R, Tilleman S, Lammertyn F, Vanhoutte I, Karimi M, Inzé D, Goossens A, Hilson P (2005) Exploration of jasmonate signalling via automated and standardized transient expression assays in tobacco cells. Plant J 44:1065–1076

    Article  Google Scholar 

  • Defaei M, Taheri-Kafrani A, Miroliaei M, Yaghmaei P (2018) Improvement of stability and reusability of α-amylase immobilized on naringin functionalized magnetic nanoparticles: a robust nanobiocatalyst. Int J Biol Macromol 113:354–360

    Article  CAS  Google Scholar 

  • Dehghan Nayeri F (2014) Identification of transcription factors linked to cell cycle regulation in Arabidopsis. Plant Signal Behav 9:e972864

    Article  Google Scholar 

  • Desgagné-Penix I, Facchini PJ (2012) Systematic silencing of benzylisoquinoline alkaloid biosynthetic genes reveals the major route to papaverine in opium poppy. Plant J 72:331–344

    Article  Google Scholar 

  • El-Sayed ER, Zaki AG, Ahmed AS, Ismaiel AA (2020) Production of the anticancer drug taxol by the endophytic fungus Epicoccum nigrum TXB502: enhanced production by gamma irradiation mutagenesis and immobilization technique. Appl Microbiol Biotechnol 104:6991–7003

    Article  CAS  Google Scholar 

  • Frerigmann H, Glawischnig E, Gigolashvili T (2015) The role of MYB34, MYB51 and MYB122 in the regulation of camalexin biosynthesis in Arabidopsis thaliana. Front Plant Sci 6:654

    Article  Google Scholar 

  • Frick S, Chitty JA, Kramell R, Schmidt J, Allen RS, Larkin PJ, Kutchan TM (2004) Transformation of opium poppy (Papaver somniferum L.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots. Transgenic Res 13:607–613

    Article  CAS  Google Scholar 

  • Fu Y, Guo H, Cheng Z, Wang R, Li G, Huo G, Liu W (2013) NtNAC-R1, a novel NAC transcription factor gene in tobacco roots, responds to mechanical damage of shoot meristem. Plant Physiol Biochem 69:74–81

    Article  CAS  Google Scholar 

  • Georgiev MI, Weber J (2014) Bioreactors for plant cells: optimization as tools for wider commercialization hardware configuration and internal environment. Biotechnol Lett 36:1359–1367

    Article  CAS  Google Scholar 

  • Glokany S, Loring RH, Glick J, Lee-Parsons CW (2009) Assessing the limitations to terpenoid indole alkaloid biosynthesis in Catharanthus roseus hairy root cultures through gene expression profiling and precursor feeding. Biotechnol Prog 25:1289–1296

    Article  Google Scholar 

  • Goyal S (2013) Ecological role of alkaloids. In: Ramawat K, Mérillon JM (eds) Natural products. Springer, Berlin

    Google Scholar 

  • Gu YQ, Yang C, Thara VK, Zhou J, Martin GB (2000) Pti4 is induced by ethylene and salicylic acid, and its product is phosphorylated by the Pto kinase. Plant Cell 12:771–785

    Article  CAS  Google Scholar 

  • Gurkok T, Ozhuner E, Parmaksiz I, Özcan S, Turktas M, İpek A, Demirtas I, Okay S, Unver T (2006) Functional characterization of 4’OMT and 7OMT genes in BIA biosynthesis. Front Plant Sci 7:98

    Google Scholar 

  • Händel EM, Alwin S, Cathomen T (2009) Expanding or restricting the target site repertoire of zinc-finger nucleases: the inter-domain linker as a major determinant of target site selectivity. Mol Ther 17:104–111

    Article  Google Scholar 

  • Hao DC, Yang L, Xiao PG, Liu M (2012) Identification of Taxus microRNAs and their targets with high-throughput sequencing and degradome analysis. Physiol Plant 146:388–403

    Article  CAS  Google Scholar 

  • Hao X, Xie C, Ruan Q, Zhang X, Wu C, Han B, Qian J, Zhou W, Nützmann HW, Ka G (2021) The transcription factor OpWRKY2 positively regulates the biosynthesis of the anticancer drug camptothecin in Ophiorrhiza pumila. Hortic Res 8:7

    Article  CAS  Google Scholar 

  • Hibi N, Higashiguchi S, Hashimoto T, Yamada Y (1994) Gene expression in tobacco low-nicotine mutants. Plant Cell 6:723–735

    CAS  Google Scholar 

  • Hosseini B, Shahriari-Ahmadi F, Hashemi H, Marashi MH, Mohseniazar M, Farokhzad A, Sabokbari M (2011) Transient expression of cor gene in Papaver somniferum. Bioimpacts 1:229–235

    CAS  Google Scholar 

  • Husen A (2022) Engıneered nanomaterials for sustainable agricultural production, soil improvement and stress management. Elsevier, Cambridge, MA

    Google Scholar 

  • Husen A, Iqbal M (2019) Nanomaterials and plant potential: an overview. In: Husen A, Iqbal M (eds) Nanomaterials and plant potential. Springer Nature, Switzerland, pp 3–29

    Chapter  Google Scholar 

  • Husen A, Rahman QI, Iqbal M, Yassin MO, Bachheti RK (2019) Plant-mediated fabrication of gold nanoparticles and their applications. In: Husen A, Iqbal M (eds) Nanomaterials and plant potential. Springer Nature, Switzerland, pp 71–110

    Chapter  Google Scholar 

  • Hussain G, Rasul A, Anwar H, Aziz N, Razzaq A, Wei W, Ali M, Li J, Li X (2018) Role of plant derived alkaloids and their mechanism in neurodegenerative disorders. Int J Biol Sci 14:341–357

    Article  CAS  Google Scholar 

  • Ilari A, Franceschini S, Bonamore A, Arenghi F, Botta B, Macone A, Pasquo A, Bellucci L, Boffi A (2009) Structural basis of enzymatic (S)-norcoclaurine biosynthesis. J Biol Chem 284:897–904

    Article  CAS  Google Scholar 

  • Imanishi S, Hashizume K, Nakakita M, Kojima H, Matsubayashi Y, Hashimoto T, Sakagami Y, Yamada Y, Nakamura K (1998) Differential induction by methyl jasmonate of genes encoding ornithine decarboxylase and other enzymes involved in nicotine biosynthesis in tobacco cell cultures. Plant Mol Biol 38:1101–1111

    Article  CAS  Google Scholar 

  • Iqbal M, Umar S, Mahmooduzzafar (2019) Nano-fertilization to enhance nutrient use efficiency and productivity of crop plants. In: Husen A, Iqbal M (eds) Nanomaterials and plant potential. Springer Nature, Switzerland, pp 473–505

    Chapter  Google Scholar 

  • Iskandar NN, Iriawati I (2016) Vinblastine and vincristine production on Madagascar peri-winkle (Catharanthus roseus (L.) G. Don) callus culture treated with polyethylene glycol. Makara J Sci 20:7–16

    Article  CAS  Google Scholar 

  • Ivanov I, Georgiev V, Pavlov A (2013) Elicitation of galanthamine biosynthesis by Leucojum aestivum liquid shoot cultures. J Plant Physiol 170:1122–1129

    Article  CAS  Google Scholar 

  • Jiang C, Lv G, Tu Y, Cheng X, Duan Y, Zeng B, He B (2021) Applications of CRISPR/Cas9 in the synthesis of secondary metabolites in filamentous fungi. Front Microbiol 12:638096

    Article  Google Scholar 

  • Kato N, Dubouzet E, Kokabu Y, Yoshida S, Taniguchi Y, Dubouzet JG, Yazaki K, Sato F (2007) Identification of a WRKY protein as a transcriptional regulator of benzylisoquinoline alkaloid biosynthesis in Coptis japonica. Plant Cell Physiol 48:8–18

    Article  CAS  Google Scholar 

  • Katoh A, Shoji T, Hashimoto T (2007) Molecular cloning of N-methylputrescine oxidase from tobacco. Plant Cell Physiol 48:550–554

    Article  CAS  Google Scholar 

  • Khan MA, Wallace WT, Islam SZ, Nagpure S, Strzalka J, Littleton JM, Rankin SE, Knutson BL (2017) Adsorption and recovery of polyphenolic flavonoids using TiO2-functionalized mesoporous silica nanoparticles. ACS Appl Mater Interfaces 9:32114–32125

    Article  CAS  Google Scholar 

  • Kim SW, Jung KH, Kwak SS, Liu JR (1994) Relationship between cell morphology and indole alkaloid production in suspension cultures of Catharanthus roseus. Plant Cell Rep 14:23–26

    Article  CAS  Google Scholar 

  • Kim YG, Cha J, Chandrasegaran S (1996) Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA 93:1156–1160

    Article  CAS  Google Scholar 

  • Kishimoto S, Sato M, Tsunematsu Y, Watanabe K (2016) Evaluation of biosynthetic pathway and engineered biosynthesis of alkaloids. Molecules 21:1078

    Article  Google Scholar 

  • Kittakoop P, Mahidol C, Ruchirawat S (2014) Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation. Curr Top Med Chem 14:239–252

    Article  CAS  Google Scholar 

  • Kohnen-Johannsen KL, Kayser O (2019) Tropane alkaloids: chemistry, pharmacology, biosynthesis and production. Molecules (Basel, Switzerland) 24:796

    Article  Google Scholar 

  • Kralova K, Jampilek J (2021) Responses of medicinal and aromatic plants to engineered nanoparticles. Appl Sci 11:1813

    Article  CAS  Google Scholar 

  • Krishnan G, Subramaniyan J, Chengalvarayan Subramani P, Muralidharan B, Thiruvengadam D (2017) Hesperetin conjugated PEGylated gold nanoparticles exploring the potential role in anti-inflammation and anti-proliferation during diethylnitrosamine-induced hepatocarcinogenesis in rats. Asian J Pharm Sci 12:442–455

    Article  Google Scholar 

  • Kumar A, Choudhary A, Kaur H, Mehta S, Husen A (2021a) Metal-based nanoparticles, sensors and their multifaceted application in food packaging. J Nanobiotechnol 19:256. https://doi.org/10.1186/s12951-021-00996-0

    Article  Google Scholar 

  • Kumar A, Choudhary A, Kaur H, Mehta S, Husen A (2021b) Smart nanomaterial and nanocomposite with advanced agrochemical activities. Nanoscale Res Lett 16:156. https://doi.org/10.1186/s11671-021-03612-0

    Article  CAS  Google Scholar 

  • Kumar A, Choudhary A, Kaur H, Guha S, Mehta S, Husen A (2022) Potential applications of engineered nanoparticles in plant disease management: a critical update. Chemosphere 295:133798. https://doi.org/10.1016/j.chemosphere.2022.133798

    Article  CAS  Google Scholar 

  • Kurek J (2019) Introductory chapter: alkaloids—their importance in nature and for human life. Intechopen

    Google Scholar 

  • La Valva V, Sabato S, Gigliano GS (1985) Morphology and alkaloid chemistry of Papaver setigerum DC. (Papaveraceae). Taxon 34:191–196

    Article  Google Scholar 

  • Legrand S, Valot N, Nicolé F, Moja S, Baudino S, Jullien F, Magnard JL, Caissard JC, Legendre L (2010) One-step identification of conserved miRNAs, their targets, potential transcription factors and effector genes of complete secondary metabolism pathways after 454 pyrosequencing of calyx cDNAs from the Labiate Salvia sclarea L. Gene 450:55–62

    Article  CAS  Google Scholar 

  • Li T, Huang S, Jiang WZ, Wright D, Spalding MH, Weeks DP, Yang B (2011) TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain. Nucleic Acids Res 39:359–372

    Article  Google Scholar 

  • Li CY, Leopold AL, Sander GW, Shanks JV, Zhao L, Gibson SI (2015a) CrBPF1 overexpression alters transcript levels of terpenoid indole alkaloid biosynthetic and regulatory genes. Front Plant Sci 6:818

    Article  Google Scholar 

  • Li F, Wang W, Zhao N, Xiao B, Cao P, Wu X, Ye C, Shen E, Qiu J, Zhu QH, Xie J, Zhou X, Fan L (2015b) Regulation of nicotine biosynthesis by an endogenous target mimicry of MicroRNA in tobacco. Plant Physiol 169:1062–1071

    Article  Google Scholar 

  • Li E, Liu H, Huang L, Zhang X, Dong X, Song W, Zhao H, Lai J (2019) Long-range interactions between proximal and distal regulatory regions in maize. Nat Commun 10:2633

    Article  Google Scholar 

  • Lichman BR (2021) The scaffold-forming steps of plant alkaloid biosynthesis. Nat Prod Rep 38:103–129

    Article  CAS  Google Scholar 

  • Liu J, Cai J, Wang R, Yang S (2016) Transcriptional regulation and transport of terpenoid indole alkaloid in Catharanthus roseus: exploration of new research directions. Int J Mol Sci 18:53

    Article  Google Scholar 

  • Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, Norville JE, Church GM (2013) RNA-guided human genome engineering via Cas9. Science 339:823–826

    Article  CAS  Google Scholar 

  • Malik S, Cusidó RM, Mirjalili MH, Moyano E, Palazón J, Bonfill M (2011) Production of the anticancer drug taxol in Taxus baccata suspension cultures: a review. Process Biochem 46(1):23–34

    Article  CAS  Google Scholar 

  • Malzahn A, Lowder L, Qi Y (2017) Plant genome editing with TALEN and CRISPR. Cell Biosci 7:21

    Article  Google Scholar 

  • Marella A, Tanwar OP, Saha R, Ali MR, Srivastava S, Akhter M, Shaquiquzzaman M, Alam MM (2013) Quinoline: a versatile heterocyclic. Saudi Pharm J 21:1–12

    Article  Google Scholar 

  • Mathiyalagan R, Subramaniyam S, Natarajan S, Kim YJ, Sun MS, Kim SY, Kim YJ, Yang DC (2013) In silico profiling of microRNAs in Korean ginseng (Panax ginseng Meyer). J Ginseng Res 37:227–247

    Article  CAS  Google Scholar 

  • Menke FL, Champion A, Kijne JW, Memelink J (1999) A novel jasmonate- and elicitor-responsive element in the periwinkle secondary metabolite biosynthetic gene Str interacts with a jasmonate- and elicitor-inducible AP2-domain transcription factor, ORCA2. EMBO J 18:4455–4463

    Article  CAS  Google Scholar 

  • Mishra S, Triptahi V, Singh S, Phukan UJ, Gupta MM, Shanker K, Shukla RK (2013) Wound induced tanscriptional regulation of benzylisoquinoline pathway and characterization of wound inducible PsWRKY transcription factor from Papaver somniferum. PLoS One 8:e52784

    Article  CAS  Google Scholar 

  • Mishra VK, Husen A, Rahman QI, Iqbal M, Sohrab SS, Yassin MO (2019) Plant-based fabrication of silver nanoparticles and their application. In: Husen A, Iqbal M (eds) Nanomaterials and plant potential. Springer Nature, Switzerland, pp 135–175

    Chapter  Google Scholar 

  • Moharrami F, Hosseini B, Sharafi A, Farjaminezhad M (2017) Enhanced production of hyoscyamine and scopolamine from genetically transformed root culture of Hyoscyamus reticulatus L. elicited by iron oxide nanoparticles. In Vitro Cell Dev Biol 53(2):104–111

    Article  CAS  Google Scholar 

  • Morishige T, Tsujita T, Yamada Y, Sato F (2000) Molecular characterization of the S-adenosyl-L-methionine:3′-hydroxy-N-methylcoclaurine 4′-O-methyltransferase involved in isoquinoline alkaloid biosynthesis in Coptis japonica. J Biol Chem 275:23398–23405

    Article  CAS  Google Scholar 

  • Nasrollahzadeh M, Sajadi SM, Iqbal M (2019) Basic chemistry and biomedical significance of nanomaterials. In: Husen A, Iqbal M (eds) Nanomaterials and plant potential. Springer Nature, Switzerland, pp 31–70

    Chapter  Google Scholar 

  • Nekrasov V, Staskawicz B, Weigel D, Jones JD, Kamoun S (2013) Targeted mutagenesis in the model plant Nicotiana benthamiana using Cas9 RNA-guided endonuclease. Nat Biotechnol 31:691–693

    Article  CAS  Google Scholar 

  • Ohme-Takagi M, Shinshi H (1995) Ethylene-inducible DNA binding proteins that interact with an ethylene-responsive element. Plant Cell 7:173–182

    CAS  Google Scholar 

  • Pan Q, Wang C, Xiong Z, Wang H, Fu X, Shen Q, Peng B, Ma Y, Sun X, 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 10:931

    Article  Google Scholar 

  • Pandey SS, Singh S, Babu CS, Shanker K, Srivastava NK, Shukla AK, Kalra A (2016) Fungal endophytes of Catharanthus roseus enhance vindoline content by modulating structural and regulatory genes related to terpenoid indole alkaloid biosynthesis. Sci Rep 6:26583

    Article  CAS  Google Scholar 

  • Pani A, Mahapatra RK (2013) Computational identification of microRNAs and their targets in Catharanthus roseus expressed sequence tags. Genom Data 1:2–6

    Article  CAS  Google Scholar 

  • Papon N, Oudin A, Vansiri A, Rideau M, CheAnieux J-C, Creche J (2003) Differential expression of two type-A response regulators in plants and cell cultures of Catharanthus roseus (L.) G. Don. J Exp Bot 54:1793–1795

    Article  CAS  Google Scholar 

  • Patra B, Pattanaik S, Schluttenhofer C, Yuan L (2018) A network of jasmonate-responsive bHLH factors modulate monoterpenoid indole alkaloid biosynthesis in Catharanthus roseus. New Phytol 217:1566–1581

    Article  CAS  Google Scholar 

  • Paul P, Singh SK, Patra B, Sui X, Pattanaik S, Yuan L (2017) A differentially regulated AP2/ERF transcription factor gene cluster acts downstream of a MAP kinase cascade to modulate terpenoid indole alkaloid biosynthesis in Catharanthus roseus. New Phytol 213:1107–1123

    Article  CAS  Google Scholar 

  • Paul P, Singh SK, Patra B, Liu X, Pattanaik S, Yuan L (2020) Mutually regulated AP2/ERF gene clusters modulate biosynthesis of specialized metabolites in plants. Plant Physiol 182:840–856

    Article  CAS  Google Scholar 

  • Pauw B, Hilliou FA, Martin VS, Chatel G, de Wolf CJ, Champion A, Pré M, van Duijn B, Kijne JW, van der Fits L, Memelink J (2004) Zinc finger proteins act as transcriptional repressors of alkaloid biosynthesis genes in Catharanthus roseus. J Biol Chem 279:52940–52948

    Article  CAS  Google Scholar 

  • Pitta-Alvarez SI, Giulietti AM (2019) Influence of chitosan, acetic acid and citric acid on growth and tropane alkaloid production in transformed roots of Brugmansia candida: effect of medium pH and growth phase. PCTOC 59:31–38

    Article  Google Scholar 

  • Prakash P, Rajakani R, Gupta V (2015) Transcriptome-wide identification of Rauvolfia serpentina microRNAs and prediction of their potential targets. Comput Biol Chem 61:62–74

    Article  Google Scholar 

  • Prasad R, Bhattacharyya A, Nguyen QD (2017) Nanotechnology in sustainable agriculture: recent developments, challenges, and perspectives. Front Microbiol 8:1014

    Article  Google Scholar 

  • Pré M, Sibéril Y, Memelink J, Champion A, Doireau P, Gantet P (2000) Isolation by the yeast one-hybrid system of cdnas encoding transcription factors that bind to the g-box element of the strictosidine synthase gene promoter from Catharanthus roseus. Int J Biochromatogr 5:229–244

    Google Scholar 

  • Qiu S, Sun H, Zhang AH, Xu HY, Yan GL, Han Y, Wang XJ (2014) Natural alkaloids: basic aspects, biological roles, and future perspectives. Chin J Nat Med 12:401–406

    CAS  Google Scholar 

  • Rizvi NF, Weaver JD, Cram EJ, Lee-Parsons CWT (2016) Silencing the transcriptional repressor, ZCT1, illustrates the tight regulation of terpenoid indole alkaloid biosynthesis in Catharanthus roseus hairy roots. PLoS One 11:e0159712

    Article  Google Scholar 

  • Rohani ER, Chiba M, Kawaharada M, Asano T, Oshima Y, Mitsuda N, Ohme-Takagi M, Fukushima A, Rai A, Saito K, Yamazak M (2016) An MYB transcription factor regulating specialized metabolisms in Ophiorrhiza Pumila. Plant Biotechnol 33:1–9

    Article  CAS  Google Scholar 

  • Ruffoni B, Pistelli L, Bertoli A, Pistelli L (2010) Plant cells cultures: bioreactors for industrial production. In: Giardi MT, Rea G, Berra B (eds) Bio-farms for nutraceuticals: functional food and safety control by biosensors. Landes Bioscience and Springer+Business Media, Germany, pp 203–221

    Chapter  Google Scholar 

  • Rushton PJ, Bokowiec MT, Han S, Zhang H, Brannock JF, Chen X, Laudeman TW, Timko MP (2008) Tobacco transcription factors: novel insights into transcriptional regulation in the Solanaceae. Plant Physiol 147:280–295

    Article  CAS  Google Scholar 

  • Russo P, Frustaci A, Del Bufalo A, Fini M, Cesario A (2013) Multitarget drugs of plants origin acting on Alzheimer’s disease. Curr Med Chem 20:1686–1693

    Article  CAS  Google Scholar 

  • Sabzehzari M, Naghavi MR (2019) Phyto-miRNAs-based regulation of metabolites biosynthesis in medicinal plants. Gene 682:13–24

    Article  CAS  Google Scholar 

  • Sakuma Y, Liu Q, Dubouzet JG, Abe H, Shinozaki K, Yamaguchi-Shinozaki K (2002) DNA-binding specificity of the ERF/AP2 domain of Arabidopsis DREBs, transcription factors involved in dehydration- and cold-inducible gene expression. Biochem Biophys Res Commun 290:998–1009

    Article  CAS  Google Scholar 

  • Sears MT, Zhang H, Rushton PJ, Wu M, Han S, Spano AJ, Timko MP (2014) NtERF32: a non-NIC2 locus AP2/ERF transcription factor required in jasmonate-inducible nicotine biosynthesis in tobacco. Plant Mol Biol 84:49–66

    Article  CAS  Google Scholar 

  • Shakeran Z, Keyhanfar M, Ashgari G, Ghanadian M (2015) Improvement of atropine production by different biotic and abiotic elicitors in hairy root cultures of Datura metel. Turk J Biol 39:111–118

    Article  CAS  Google Scholar 

  • Sharma P, Pandey V, Sharma MMM, Patra A, Singh B, Mehta S, Husen A (2021) A review on biosensors and nanosensors application in agroecosystems. Nanoscale Res Lett 16:136. https://doi.org/10.1186/s11671-021-03593-0

    Article  Google Scholar 

  • Shoji T, Hashimoto T (2011a) Tobacco MYC2 regulates jasmonate-inducible nicotine biosynthesis genes directly and by way of the NIC2-locus ERF genes. Plant Cell Physiol 52:1117–1130

    Article  CAS  Google Scholar 

  • Shoji T, Hashimoto T (2011b) Recruitment of a duplicated primary metabolism gene into the nicotine biosynthesis regulon in tobacco. Plant J 67:949–959

    Article  CAS  Google Scholar 

  • Shoji T, Inai K, Yazaki Y, Sato Y, Takase H, Shitan N, Yazaki K, Goto Y, Toyooka K, Matsuoka K, Hashimoto T (2009) Multidrug and toxic compound extrusion-type transporters implicated in vacuolar sequestration of nicotine in tobacco roots. Plant Physiol 149:708–718

    Article  CAS  Google Scholar 

  • Shoji T, Kajikawa M, Hashimoto T (2010) Clustered transcription factor genes regulate nicotine biosynthesis in tobacco. Plant Cell 22:3390–3409

    Article  CAS  Google Scholar 

  • Siberil Y, Benhamron S, Memelink J, Giglioli-Guivarc’h N, Thiersault M, Boisson B, Gantet P (2001) Catharanthus roseus G-box binding factors 1 and 2 act as repressors of strictosidine synthase gene expression in cell cultures. Plant Mol Biol 45:477–488

    Article  CAS  Google Scholar 

  • Siddiqi KS, Husen A (2021) Plant response to silver nanoparticles: a critical review. Crit Rev Biotechnol. https://doi.org/10.1080/07388551.2021.1975091

  • Singh N, Srivastava S, Shasany A, Sharma A (2016) Identification of miRNAs and their targets involved in the secondary metabolic pathways of Mentha spp. Comput Biol Chem 64:154–162

    Article  CAS  Google Scholar 

  • Singh J, Mehta A, Rawat M, Basu S (2018) Green synthesis of silver nanoparticles using sun dried tulsi leaves and its catalytic application for 4-Nitrophenol reduction. J Environ Chem Eng 6:1468–1474

    Article  CAS  Google Scholar 

  • Singh SK, Patra B, Paul P, Liu Y, Pattanaik S, Yuan L (2020) Revisiting the ORCA gene cluster that regulates terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Plant Sci 293:110408

    Article  CAS  Google Scholar 

  • Singla R, Kumari A, Yadav SK (2019) Impact of nanomaterials on plant physiology and functions. In: Husen A, Iqbal M (eds) Nanomaterials and plant potential. Springer Nature, Switzerland, pp 349–378

    Chapter  Google Scholar 

  • Smith JI, Smart NJ, Kurz WGW, Misawa M (1987) The use of organic and inorganic compounds to increase the accumulation of indole alkaloids in Catharanthus roseus (L.) G. Don cell suspension cultures. J Exp Bot 38:1501–1506

    Article  CAS  Google Scholar 

  • Sobhani Najafabadi A, Naghavi M (2018) Mining ferula gummosa transcriptome to identify miRNAs involved in the regulation and biosynthesis of terpenes. Gene 645:41–47

    Article  CAS  Google Scholar 

  • Sofowora A, Ogunbodede E, Onayade A (2013) The role and place of medicinal plants in the strategies for disease prevention. Afr J Tradit Complement Altern Med 10:210–229

    Google Scholar 

  • Sui X, Singh SK, Patra B, Schluttenhofer C, Guo W, Pattanaik S, Yuan L (2018) Cross-family transcription factor interaction between MYC2 and GBFs modulates terpenoid indole alkaloid biosynthesis. J Exp Bot 69:4267–4281

    Article  CAS  Google Scholar 

  • Sui X, Zhang H, Song Z, Gao Y, Li W, Li M, Zhao L, Li Y, Wang B (2019) Ethylene response factor NtERF91 positively regulates alkaloid accumulations in tobacco (Nicotiana tabacum L.). Biochem Biophys Res Commun 517:164–171

    Article  CAS  Google Scholar 

  • Sui X, He X, Song Z, Gao Y, Zhao L, Jiao F (2021) The gene NtMYC2a acts as a “master switch” in the regulation of JA-induced nicotine accumulation in tobacco. Plant 23:317–326

    CAS  Google Scholar 

  • Suttipanta N, Pattanaik S, Kulshrestha M, Patra B, Singh SK, Yuan L (2011) The transcription factor CrWRKY1 positively regulates the terpenoid indole alkaloid biosynthesis in Catharanthus roseus. Plant Physiol 157:2081–2093

    Article  CAS  Google Scholar 

  • Taghizadeh M, Nasibi F, Kalantari KM, Ghanati F (2019) Evaluation of secondary metabolites and antioxidant activity in Dracocephalum polychaetum Bornm. cell suspension culture under magnetite nanoparticles and static magnetic field elicitation. Plant Cell Tissue Organ Cult 136:489–498

    Article  CAS  Google Scholar 

  • Talbot NJ (2015) Plant immunity: a little help from fungal friends. Curr Biol 25:R1074–R1076

    Article  CAS  Google Scholar 

  • Thagun C, Imanishi S, Kudo T, Nakabayashi R, Ohyama K, Mori T, Kawamoto K, Nakamura Y, Katayama M, Nonaka S, Matsukura C, Yano K, Ezura H, Saito K, Hashimoto T, Shoji T (2016) Jasmonate-responsive ERF transcription factors regulate steroidal glycoalkaloid biosynthesis in tomato. Plant Cell Physiol 57:961–975

    Article  CAS  Google Scholar 

  • Thawabteh A, Juma S, Bader M, Karaman D, Scrano L, Bufo SA, Karaman R (2019) The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins (Basel) 11:656

    Article  CAS  Google Scholar 

  • Todd AT, Liu E, Polvi SL, Pammett RT, Page JE (2010) A functional genomics screen identifies diverse transcription factors that regulate alkaloid biosynthesis in Nicotiana benthamiana. Plant J 62:589–600

    Article  CAS  Google Scholar 

  • Udomsom N, Rai A, Suzuki H, Okuyama J, Imai R, Mori T, Nakabayashi R, Saito K, Yamazaki M (2016) Function of AP2/ERF transcription factors involved in the regulation of specialized metabolism in Ophiorrhiza pumila revealed by transcriptomics and metabolomics. Front Plant Sci 7:1861

    Article  Google Scholar 

  • Unver T, Parmaksiz I, Dundar E (2010) Identification of conserved micro-RNAs and their target transcripts in opium poppy (Papaver somniferum L.). Plant Cell Rep 29:757–769

    Article  CAS  Google Scholar 

  • Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, Jamieson AC, Porteus MH, Gregory PD, Holmes MC (2005) Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435:646–651

    Article  CAS  Google Scholar 

  • Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11:636–646

    Article  CAS  Google Scholar 

  • van der Fits L, Memelink J (2000) ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and secondary metabolism. Science 289:295–297

    Article  Google Scholar 

  • Van der Fits L, Zhang H, Menke FLH, Deneka M, Memelink JA (2000) Catharanthus Roseus BPF-1 homologue interacts with an elicitor-responsive region of the secondary metabolite biosynthetic gene Str and Is induced by elicitor via a JA-independent signal transduction pathway. Plant Mol Biol 44:675–685

    Article  Google Scholar 

  • Vashisht I, Mishra P, Pal T (2015) Mining NGS transcriptomes for miRNAs and dissecting their role in regulating growth, development, and secondary metabolites production in different organs of a medicinal herb, Picrorhiza kurroa. Planta 241:1255–1268

    Article  CAS  Google Scholar 

  • Waheed S, Zeng L (2020) The critical role of miRNAs in regulation of flowering time and flower development. Genes (Basel) 11:319

    Article  CAS  Google Scholar 

  • Wang B, Lewis RS, Shi J, Song Z, Gao Y, Li W, Chen H, Qu R (2015) Genetic factors for enhancement of nicotine levels in cultivated tobacco. Sci Rep 5:17360

    Article  CAS  Google Scholar 

  • Wang C, Wu C, Wang Y, Xie C, Shi M, Nile S, Zhou Z, Kai G (2019) Transcription factor OpWRKY3 Is involved in the development and biosynthesis of camptothecin and its precursors in Ophiorrhiza pumila hairy roots. Int J Mol Sci 20:3996

    Article  CAS  Google Scholar 

  • Wink M (1999) Plant secondary metabolites from higher plants: biochemistry, function and biotechnology. In: Wink M (ed) Biochemistry of plant secondary metabolism, annual plant reviews, vol 2. Sheffield Academic, Sheffield, pp 1–16

    Google Scholar 

  • Woo JW, Kim J, Kwon SI, Corvalán C, Cho SW, Kim H, Kim SG, Kim ST, Choe S, Kim JS (2015) DNA-free genome editing in plants with preassembled CRISPR-Cas9 ribonucleoproteins. Nat Biotechnol 33:1162–1164

    Article  CAS  Google Scholar 

  • Xu M, Wu C, Zhao L, Wang Y, Wang C, Zhou W, Ming Y, Kai G (2020) WRKY transcription factor OpWRKY1 acts as a negative regulator of camptothecin biosynthesis in Ophiorrhiza pumila hairy roots. Plant Cell Tissue Organ Cult 142:69–78

    Article  CAS  Google Scholar 

  • Yamada Y, Sato F (2013) Transcription factors in alkaloid biosynthesis. Int Rev Cell Mol Biol 305:339–382

    Article  CAS  Google Scholar 

  • Yamada Y, Kokabu Y, Chaki K, Yoshimoto T, Ohgaki M, Yoshida S, Kato N, Koyama T, Sato F (2011) Isoquinoline alkaloid biosynthesis is regulated by a unique bHLH-type transcription factor in Coptis japonica. Plant Cell Physiol 52:1131–1141

    Article  CAS  Google Scholar 

  • Yamamoto O, Yamada Y (1987) Selection of reserpine producing cell strain using UV-light and optimization of reserpine production in the selected cell strain. Plant Cell Tissue Organ Cult 8:125–133

    Article  CAS  Google Scholar 

  • Yuan CG, Huo C, Gui B, Liu P, Zhang C (2017) Green synthesis of silver nanoparticles using Chenopodium aristatum L. stem extract and their catalytic/antibacterial activities. J Clust Sci 28:1319–1333

    Article  CAS  Google Scholar 

  • Zhang H, Hedhili S, Montiel G, Zhang Y, Chatel G, Pré M, Gantet P, Memelink J (2011) The basic helix-loop-helix transcription factor CrMYC2 controls the jasmonate-responsive expression of the ORCA genes that regulate alkaloid biosynthesis in Catharanthus roseus. Plant J 67:61–71

    Article  CAS  Google Scholar 

  • Zhang HB, Bokowiec MT, Rushton PJ, Han SC, Timko MP (2012) Tobacco transcription factors NtMYC2a and NtMYC2b form nuclear complexes with the NtJAZ1 repressor and regulate multiple jasmonate-inducible steps in nicotine biosynthesis. Mol Plant 5:73–84

    Article  CAS  Google Scholar 

  • Zhao J, Hu Q, Guo YQ, Zhu WH (2001) Effects of stress factors, bioregulators, and synthetic precursors on indole alkaloid production in compact callus clusters cultures of Catharanthus roseus. Appl Microbiol Biotechnol 55:693–698

    Article  CAS  Google Scholar 

  • Zheng Z, Wu M (2004) Cadmium treatment enhances the production of alkaloid secondary metabolites in Catharanthus roseus. Plant Sci 166:507–514

    Article  CAS  Google Scholar 

  • Zhou M, Memelink J (2016) Jasmonate-responsive transcription factors regulating plant secondary metabolism. Biotechnol Adv 34:441–449

    Article  Google Scholar 

  • Zhu L, Chen L (2019) Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett 24:40

    Article  CAS  Google Scholar 

  • Ziegler J, Facchini PJ (2008) Alkaloid biosynthesis: metabolism and trafficking. Annu Rev Plant Biol 59:735–769

    Article  CAS  Google Scholar 

  • Ziegler J, Diaz-Chávez ML, Kramell R, Ammer C, Kutchan TM (2005) Comparative macroarray analysis of morphine containing Papaver somniferum and eight morphine free Papaver species identifies an O-methyltransferase involved in benzylisoquinoline biosynthesis. Planta 222:458–471

    Article  CAS  Google Scholar 

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Bhushan, S., Sharma, D., Rakshant, Kaul, S., Dhar, M.K., Sharma, M. (2023). Recent Strategies to Engineer Alkaloid Biosynthesis in Medicinal Plants. In: Husen, A., Iqbal, M. (eds) Medicinal Plants. Springer, Singapore. https://doi.org/10.1007/978-981-19-5611-9_15

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