The Role of Agrobacterium-Mediated and Other Gene-Transfer Technologies in Cannabis Research and Product Development

Chapter

Abstract

Cannabis sativa is a multi-use crop valued for its pharmacological properties and as a fibre and seed crop. Biotechnological applications toward Cannabis research and product development are still in their early stages. An important feature of biotechnology is the collection of gene transfer technologies that are used to introduce genetic material into host organisms. Agrobacterium tumefaciens and A. rhizogenes represent the most common vectors to transfer genetic material into plant cells. Stable and transient gene expression can be achieved using A. tumefaciens while A. rhizogenes generates stable transformed hairy roots. Cannabis is amenable to genetic transformation using both Agrobacterium vectors, however the plant is recalcitrant to regeneration, impeding the recovery of transgenic Cannabis plants. Despite this shortcoming, the cannabinoid pathway is currently attracting considerable attention from the biotechnology community. Gene transfer technologies have assisted with the characterization of the cannabinoid pathway leading to the synthesis of THCA, the psychoactive compound that is highly valued as a therapeutic. Elucidation of the cannabinoid pathway has led to its metabolic engineering in heterologous hosts. The yeast Pichia pastoris has proven to be a particularly suitable host for the production of cannabinoids. Recently, biotechnology companies have emerged that anticipate commercializing cannabinoid-based drugs in yeast and tobacco and to produce hemp cultivars with the cannabinoid pathway down-regulated or completely knocked out.

Notes

Acknowledgements

This work was supported by a BBSRC grant (BB/J017582/1) for MF and an NSERC Discovery Grant to ZKP.

References

  1. Ahmad M, Hirz M, Pichler H, Schwab H (2014) Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production. Appl Microbiol Biotechnol 98:5301–5317PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ahmad R, Tehsin Z, Malik ST, Asad SA, Shahzad M, Bilal M, Shah MM, Khan SA (2016) Phytoremediation potential of hemp (Cannabis sativa L.): identification and characterization of heavy metals responsive genes. Clean Soil Air Water 44:195–201CrossRefGoogle Scholar
  3. Ajikumar PK, Xiao W-H, Tyo KEJ, Wang Y, Simeon F, Leonard E, Mucha O, Phon TH, Pfeifer B, Stephanopoulos G (2010) Isoprenoid pathway optimization for taxol precursor overproduction in Escherichia coli. Science 330:70–74PubMedPubMedCentralCrossRefGoogle Scholar
  4. Altpeter F, Springer NM, Bartley LE, Blechl A, Brutnell TP, Citovsky V, Conrad L, Gelvin SB, Jackson D, Kausch AP, Lemaux PG, Medford JI, Orozo-Cardenas M, Tricoli D, VanEck J, Voytas DF, Walbot V, Wang K, Zhang ZJ, Stewart CN (2016) Advancing crop transformation in the era of genome editing. Plant Cell 28:1510–1520PubMedPubMedCentralGoogle Scholar
  5. Andre CM, Hausman JF, Guerriero G (2016) Cannabis sativa: the plant of the thousand and one molecules. Frontiers Plant Sci 7:19CrossRefGoogle Scholar
  6. Baghaei B, Skrifvars M, Salehi M, Bashir T, Rissanen M, Nousiainen P (2014) Novel aligned hemp fibre reinforcement for structural biocomposites: porosity, water absorption, mechanical performances and viscoelastic behaviour. Compos A 61:1–12CrossRefGoogle Scholar
  7. Baker D, Pryce G, Giovannoni G, Thompson AJ (2003) The therapeutic potential of cannabis. Lancet Neurol 2:291–298PubMedCrossRefGoogle Scholar
  8. Bell J (2016) Marijuana compounds brewed using yeast by Canadian biotech firms. CBC News. Retrieved from http://www.cbc.ca/news/technology/medical-marijuana-yeast-1.3527950
  9. Bifulco M, Pisanti S (2015) Medicinal use of cannabis in Europe: the fact that more countries legalize the medicinal use of cannabis should not become an argument for unfettered and uncontrolled use. EMBO Rep 16:130–132PubMedPubMedCentralCrossRefGoogle Scholar
  10. Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ (2015) Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 13:42–51PubMedCrossRefGoogle Scholar
  11. Bock R (2010) The give-and-take of DNA: horizontal gene transfer in plants. Trends Plant Sci 15:11–22PubMedCrossRefGoogle Scholar
  12. Bolognini D, Costa B, Maione S, Comelli F, Marini P, Di Marzo V, Parolaro D, Ross RA, Gauson LA, Cascio MG, Pertwee RG (2010) The plant cannabinoid Δ9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice. Br J Pharmacol 160:677–687PubMedPubMedCentralCrossRefGoogle Scholar
  13. Borrelli F, Fasolino I, Romano B, Capasso R, Maiello F, Coppola D, Orlando P, Battista G, Pagano E, Di Marzo V, Izzo AA (2013) Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease. Biochem Pharmacol 85:1306–1316PubMedCrossRefGoogle Scholar
  14. Brockstein A (2016) Biosynthesis could radically change the Cannabis industry. New Cannabis Ventures. Retrieved from https://www.newcannabisventures.com/biosynthesis-could-radically-change-the-cannabis-industry/
  15. Callaway JC (2004) Hempseed as a nutritional resource: an overview. Euphytica 140:65–72CrossRefGoogle Scholar
  16. Campbell S, Paquin D, Awaya JD, Li QX (2002) Remediation of benzo[a]pyrene and chrysene-contaminated soil with industrial hemp (Cannabis sativa). Int J Phytoremediat 4:157–168CrossRefGoogle Scholar
  17. Carus M, Karst S, Kauffmann A, Hobson J, Bertucelli S (2013) The European hemp industry: cultivation, processing and applications for fibres, shivs and seeds. European Industrial Hemp Association, Hürth, Germany, pp 1–9. Retrieved from http://eiha.org/media/2014/10/13-06-European-Hemp-Industry.pdf
  18. Chattopadhyay T, Roy S, Mitra A, Maiti MK (2011) Development of a transgenic hairy root system in jute (Corchorus capsularis L.) with gusA reporter gene through Agrobacterium rhizogenes mediated co-transformation. Plant Cell Rep 30:485–493PubMedCrossRefGoogle Scholar
  19. Chilton M-D (2001) Agrobacterium. A memoir. Plant Physiol 125:9–14PubMedPubMedCentralCrossRefGoogle Scholar
  20. Chilton M-D, Drummond MH, Merlo DJ, Sciaky D, Montoya AL, Gordon MP, Nester EW (1977) Stable incorporation of plasmid DNA into higher plant cells: the molecular basis of crown gall tumorigenesis. Cell 11:263–271PubMedCrossRefGoogle Scholar
  21. Chilton M-D, Tepfer DA, Petit A, David C, Casse-Delbart F, Tempe J (1982) Agrobacterium rhizogenes inserts T-DNA into the genomes of the host plant root cells. Nature 295:432–434CrossRefGoogle Scholar
  22. Conley AJ, Zhu H, Le LC, Jevnikar AM, Lee BH, Brandle JE, Menassa R (2011) Recombinant protein production in a variety of Nicotiana hosts: a comparative analysis. Plant Biotechnol J 9:434–444PubMedCrossRefGoogle Scholar
  23. Crew BEC (2015) Scientists engineer yeast to produce active marijuana compound, THC. Science Alert. Retrieved from http://www.sciencealert.com/scientists-engineer-yeast-to-produce-active-marijuana-compound-thc
  24. Cui H, Zhang S-T, Yang H-J, Ji H, Wang X-J (2011) Gene expression profile analysis of tobacco leaf trichomes. BMC Plant Biol 11:1–10CrossRefGoogle Scholar
  25. Das A, Chaudhury S, Kalita MC, Mondal TK (2015) In silico identification, characterization and expression analysis of miRNAs in Cannabis sativa L. Plant Gene 2:17–24CrossRefGoogle Scholar
  26. Day RN, Davidson MW (2009) The fluorescent protein palette: tools for cellular imaging. Chem Soc Rev 38:2887–2921PubMedPubMedCentralCrossRefGoogle Scholar
  27. Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, Katz R, Di Marzo V, Jutras-Aswad D, Notcutt WG, Martinez-Orgado J, Robson PJ, Rohrback BG, Thiele E, Whalley B, Friedman D (2014) Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia 55:791–802PubMedPubMedCentralCrossRefGoogle Scholar
  28. Dong J-Z, McHughen A (1993) Transgenic flax plants from Agrobacterium mediated transformation: incidence of chimeric regenerants and inheritance of transgenic plants. Plant Sci 91:139–148CrossRefGoogle Scholar
  29. Ebskamp MJ (2002) Engineering flax and hemp for an alternative to cotton. Trends Biotechnol 20:229–230PubMedCrossRefGoogle Scholar
  30. Elsohly MA, Slade D (2005) Chemical constituents of marijuana: the complex mixture of natural cannabinoids. Life Sci 78:539–548PubMedCrossRefGoogle Scholar
  31. Escobar MA, Dandekar AM (2003) Agrobacterium tumefaciens as an agent of disease. Trends Plant Sci 8:380–386PubMedCrossRefGoogle Scholar
  32. Feeney M, Punja ZK (2003) Tissue culture and Agrobacterium-mediated transformation of hemp (Cannabis sativa L.). In Vitro Cell Dev Biol Plant 39:578–585CrossRefGoogle Scholar
  33. Feeney M, Punja ZK (2015) Hemp (Cannabis sativa L.). Meth Mol Biol 1224:319–329CrossRefGoogle Scholar
  34. Fisse J, Braut F, Cosson L, Paris M (1981) Étude in vitro des capacités organogénétiques de tissus de Cannabis sativa L.; effet de différentes substances de croissance. Pl Méd Phytoth 15:217–223Google Scholar
  35. Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE (2012) Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc Nat Acad Sci 109:12811–12816PubMedPubMedCentralCrossRefGoogle Scholar
  36. Galasso I, Russo R, Mapelli S, Ponzoni E, Brambilla IM, Battelli G, Reggiani R (2016) Variability in seed traits in a collection of Cannabis sativa L. genotypes. Frontiers Plant Sci 7:688Google Scholar
  37. Gelvin SB (2003) Agrobacterium-mediated plant transformation: the biology behind the “gene-jockeying” tool. Microbiol Mol Biol Rev 67:16–37PubMedPubMedCentralCrossRefGoogle Scholar
  38. Gelvin SB (2012) Traversing the cell: Agrobacterium T-DNA’s journey to the host genome. Frontiers Plant Sci 3:52CrossRefGoogle Scholar
  39. Gertsch J, Pertwee RG, Di Marzo V (2010) Phytocannabinoids beyond the Cannabis plant—do they exist? Br J Pharmacol 160:523–529PubMedPubMedCentralCrossRefGoogle Scholar
  40. González-García S, Hospido A, Feijoo G, Moreira MT (2010) Life cycle assessment of raw materials for non-wood pulp mills: hemp and flax. Resour Conserv Recy 54:923–930CrossRefGoogle Scholar
  41. Haag A (2016) 22nd Century launches major new initiative to produce medically-important marijuana cannabinoids. Business Wire. Retrieved from http://www.businesswire.com/news/home/20160512005770/en/
  42. Hansen G, Wright MS (1999) Recent advances in the transformation of plants. Trends Plant Sci 4:226–231PubMedCrossRefGoogle Scholar
  43. Happyana N, Agnolet S, Muntendam R, Van Dam A, Schneider B, Kayser O (2013) Analysis of cannabinoids in laser-microdissected trichomes of medicinal Cannabis sativa using LCMS and cryogenic NMR. Phytochemistry 87:51–59PubMedCrossRefGoogle Scholar
  44. Hellens R, Mullineaux P, Klee H (2000) Technical focus: a guide to Agrobacterium binary Ti vectors. Trends Plant Sci 5:446–451PubMedCrossRefGoogle Scholar
  45. Hemphill JK, Turner JC, Mahlberg PG (1978) Studies on growth and cannabinoid composition of callus derived from different strains of Cannabis sativa. Lloydia 41:453–462Google Scholar
  46. Hill AJ, Williams CM, Whalley BJ, Stephens GJ (2012) Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Therapeut 133:79–97CrossRefGoogle Scholar
  47. Hodgkins K (2015) Scientists genetically engineer yeast to make THC and other medical marijuana chemicals. Digital Trends. Retrieved from http://www.digitaltrends.com/cool-tech/thc-yeast-medical-marijuana/
  48. Hoekema A, Hirsch PR, Hooykaas PJJ, Schilperoort RA (1983) A binary plant vector strategy based on separation of vir- and T-region of the Agrobacterium tumefaciens Ti-plasmid. Nature 303:179–180CrossRefGoogle Scholar
  49. Hofmann ME, Frazier CJ (2013) Marijuana, endocannabinoids, and epilepsy: potential and challenges for improved therapeutic intervention. Exp Neurol 244:43–50PubMedCrossRefGoogle Scholar
  50. Joensuu JJ, Conley AJ, Lienemann M, Brandle JE, Linder MB, Menassa R (2010) Hydrophobin fusions for high-level transient protein expression and purification in Nicotiana benthamiana. Plant Physiol 152:622–633PubMedPubMedCentralCrossRefGoogle Scholar
  51. Jones NA, Glyn SE, Akiyama S, Hill TD, Hill AJ, Weston SE, Burnett MD, Yamasaki Y, Stephens GJ, Whalley BJ, Williams CM (2012) Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure 21:344–352PubMedCrossRefGoogle Scholar
  52. Kapila J, De Rycke R, Van Montagu M, Angenon G (1997) An Agrobacterium-mediated transient gene expression system for intact leaves. Plant Sci 122:101–108CrossRefGoogle Scholar
  53. Khamsi R (2015) Newly risen from yeast: THC. The New York Times. Retrieved from http://www.nytimes.com/2015/09/15/science/newly-risen-from-yeast-thc.html
  54. Kim JT, Netravali AN (2011) Development of aligned-hemp yarn-reinforced green composites with soy protein resin: effect of pH on mechanical and interfacial properties. Compos Sci Technol 71:541–547CrossRefGoogle Scholar
  55. Kost TA, Condreay JP, Jarvis DL (2005) Baculovirus as versatile vectors for protein expression in insect and mammalian cells. Nat Biotechnol 23:567–575PubMedPubMedCentralCrossRefGoogle Scholar
  56. Kyndt T, Quispe D, Zhai H, Jarret R, Ghislain M, Liu Q, Gheysen G, Kreuze JF (2015) The genome of cultivated sweet potato contains Agrobacterium T-DNAs with expressed genes: an example of a naturally transgenic food crop. Proc Nat Acad Sci 112:5844–5849PubMedPubMedCentralCrossRefGoogle Scholar
  57. Laate EA (2012) Industrial hemp production in Canada. Retrieved from the Government of Alberta, Agriculture and Rural Development Department website: http://www1.agric.gov.ab.ca/$department/deptdocs.nsf/all/econ9631
  58. Lange BM, Turner GW (2013) Terpenoid biosynthesis in trichomes—current status and future opportunities. Plant Biotechnol J 11:2–22PubMedCrossRefGoogle Scholar
  59. Lata H, Chandra S, Khan I, ElSohly MA (2009) Thidiazuron-induced high-frequency direct shoot organogenesis of Cannabis sativa L. In Vitro Cell Dev Biol Plant 45:12–19CrossRefGoogle Scholar
  60. Lata H, Chandra S, Khan IA, Elsohly MA (2010) High frequency plant regeneration from leaf derived callus of high Δ9-tetrahydrocannabinol yielding Cannabis sativa L. Planta Med 76:1629–1633PubMedCrossRefGoogle Scholar
  61. Lebrun G, Couture A, Laperrière L (2013) Tensile and impregnation behavior of unidirectional hemp/paper/epoxy and flax/paper/epoxy composites. Compos Struct 103:151–160CrossRefGoogle Scholar
  62. Lim CG, Fowler ZL, Hueller T, Schaffer S, Koffas MA (2011) High-yield resveratrol production in engineered Escherichia coli. Appl Environ Microbiol 77:3451–3460PubMedPubMedCentralCrossRefGoogle Scholar
  63. Linger P, Müssig J, Fischer H, Kobert J (2002) Industrial hemp (Cannabis sativa L.) growing on heavy metal contaminated soil: fibre quality and phytoremediation potential. Ind Crop Prod 16:33–42CrossRefGoogle Scholar
  64. MacKinnon L, Mc Dougall G, Aziz N, Millam S (2000) Progress towards transformation of fibre hemp. Scottish Crop Research Institute Annual Report 2000/2001. Scottish Crop Research Institute, Invergowrie, Dundee, pp 84–86Google Scholar
  65. Mahlberg PG, Kim ES (2004) Accumulation of cannabinoids in glandular trichomes of Cannabis (Cannabaceae). J Ind Hemp 9:15–36CrossRefGoogle Scholar
  66. Marks MD, Tian L, Wenger JP, Omburo SN, Soto-Fuentes W, He J, Gang DR, Weiblen GD, Dixon RA (2009) Identification of candidate genes affecting Δ9-tetrahydrocannabinol biosynthesis in Cannabis sativa. J Exp Bot 60:3715–3726PubMedPubMedCentralCrossRefGoogle Scholar
  67. Mathur A, Gangwar A, Mathur AK, Verma P, Uniyal GC, Lal RK (2010) Growth kinetics and ginsenosides production in transformed hairy roots of American ginseng—Panax quinquefolium L. Biotechnol Lett 32:457–461PubMedCrossRefGoogle Scholar
  68. Matveeva TV, Lutova LA (2014) Horizontal gene transfer from Agrobacterium to plants. Frontiers Plant Sci 5:326CrossRefGoogle Scholar
  69. Menassa R, Zhu H, Karatzas CN, Lazaris A, Richman A, Brandle J (2004) Spider dragline silk proteins in transgenic tobacco leaves: accumulation and field production. Plant Biotechnol J 2:431–438PubMedCrossRefGoogle Scholar
  70. Miyawaki A (2011) Proteins on the move: insights gained from fluorescent protein technologies. Nat Rev Mol Cell Biol 12:656–668PubMedCrossRefGoogle Scholar
  71. Moore L, Warren G, Strobel G (1979) Involvement of a plasmid in the hairy root disease of plants caused by Agrobacterium rhizogenes. Plasmid 2:617–626PubMedCrossRefGoogle Scholar
  72. O’Keefe BR, Vojdani F, Buffa V, Shattock RJ, Montefiori DC, Bakke J, Mirsalis J, d’Andrea AL, Hume SD, Bratcher B, Saucedo CJ, McMahon JB, Pogue GP, Palmer KE (2009) Scaleable manufacture of HIV-1 entry inhibitor griffithsin and validation of its safety and efficacy as a topical microbicide component. Proc Nat Acad Sci 106:6099–6104PubMedPubMedCentralCrossRefGoogle Scholar
  73. Oksman-Caldentey KM, Inze D (2004) Plant cell factories in the post-genomic era: new ways to produce designer secondary metabolites. Trends Plant Sci 9:433–440PubMedCrossRefGoogle Scholar
  74. Ono NN, Tian L (2011) The multiplicity of hairy root cultures: prolific possibilities. Plant Sci 180:439–446PubMedCrossRefGoogle Scholar
  75. Păcurar DI, Thordal-Christensen H, Păcurar ML, Pamfil D, Botez C, Bellini C (2011) Agrobacterium tumefaciens: from crown gall tumors to genetic transformation. Physiol Mol Plant Path 76:76–81CrossRefGoogle Scholar
  76. Pertwee RG (2004) Pharmacological and therapeutic targets for Δ9-tetrahydrocannabinol and cannabidiol. Euphytica 140:73–82CrossRefGoogle Scholar
  77. Raboy V (2007) The ABCs of low-phytate crops. Nat Biotechnol 25:874–875PubMedCrossRefGoogle Scholar
  78. Raharjo TJ, Chang WT, Verberne MC, Peltenburg-Looman AM, Linthorst HJ, Verpoorte R (2004) Cloning and over-expression of a cDNA encoding a polyketide synthase from Cannabis sativa. Plant Physiol Biochem 42:291–297PubMedCrossRefGoogle Scholar
  79. Ranalli P, Venturi G (2004) Hemp as a raw material for industrial applications. Euphytica 140:1–6CrossRefGoogle Scholar
  80. Rehm J, Fischer B (2015) Cannabis legalization with strict regulation, the overall superior policy option for public health. Clin Pharmacol Ther 97:541–544PubMedCrossRefGoogle Scholar
  81. Richez-Dumanois C, Braut-Boucher F, Cosson L, Paris M (1986) Multiplication végétative in vitro du chanvre (Cannabis sativa L.). Application à la conservation des clones sélectionnés. Agronomie 6:487–495CrossRefGoogle Scholar
  82. Ron M, Kajala K, Pauluzzi G, Wang D, Reynoso MA, Zumstein K, Garcha J, Winte S, Masson H, Inagaki S, Federici F, Sinha N, Deal RB, Bailey-Serres J, Brady SM (2014) Hairy root transformation using Agrobacterium rhizogenes as a tool for exploring cell type-specific gene expression and function using tomato as a model. Plant Physiol 166:455–469PubMedPubMedCentralCrossRefGoogle Scholar
  83. Salentijn EMJ, Zhang Q, Amaducci S, Yang M, Trindade LM (2015) New developments in fiber hemp (Cannabis sativa L.) breeding. Ind Crop Prod 68:32–41CrossRefGoogle Scholar
  84. Shahzad A (2012) Hemp fiber and its composites—a review. J Compos Mater 46:973–986CrossRefGoogle Scholar
  85. Shi J, Wang H, Schellin K, Li B, Faller M, Stoop JM, Meeley RB, Ertl DS, Ranch JP, Glassman K (2007) Embryo-specific silencing of a transporter reduces phytic acid content of maize and soybean seeds. Nat Biotechnol 25:930–937PubMedCrossRefGoogle Scholar
  86. Shi G, Liu C, Cui M, Ma Y, Cai Q (2012) Cadmium tolerance and bioaccumulation of 18 hemp accessions. Appl Biochem Biotech 168:163–173CrossRefGoogle Scholar
  87. Singh OV, Jain RK (2003) Phytoremediation of toxic aromatic pollutants from soil. Appl Microbiol Biot 63:128–135CrossRefGoogle Scholar
  88. Sirikantaramas S, Morimoto S, Shoyama Y, Ishikawa Y, Wada Y, Shoyama Y, Taura F (2004) The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of Δ1-tetrahydrocannabinolic acid synthase from Cannabis sativa L. J Biol Chem 279:39767–39774PubMedCrossRefGoogle Scholar
  89. Sirikantaramas S, Taura F, Tanaka Y, Ishikawa Y, Morimoto S, Shoyama Y (2005) Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes. Plant Cell Physiol 46:1578–1582PubMedCrossRefGoogle Scholar
  90. Slusarkiewicz-Jarzina A, Ponitka A, Kaczmarek Z (2005) Influence of cultivar, explant source and plant growth regulator on callus induction and plant regeneration of Cannabis sativa L. Acta Biol Crac Ser Bot 47:145–151Google Scholar
  91. Sparkes IA, Runions J, Kearns A, Hawes C (2006) Rapid, transient expression of fluorescent fusion proteins in tobacco plants and generation of stably transformed plants. Nat Protoc 1:2019–2025PubMedCrossRefGoogle Scholar
  92. Spithoff S, Emerson B, Spithoff A (2015) Cannabis legalization: adhering to public health best practice. Can Med Assoc J 187:1211–1216CrossRefGoogle Scholar
  93. Srivastava S, Srivastava AK (2007) Hairy root culture for mass-production of high-value secondary metabolites. Crit Rev Biotechnol 27:29–43PubMedCrossRefGoogle Scholar
  94. Stott CG, Guy GW (2004) Cannabinoids for the pharmaceutical industry. Euphytica 140:83–93CrossRefGoogle Scholar
  95. Stout JM, Boubakir Z, Ambrose SJ, Purves RW, Page JE (2012) The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes. Plant J 71:353–365PubMedGoogle Scholar
  96. Sun X, Hu Z, Chen R, Jiang Q, Song G, Zhang H, Xi Y (2015) Targeted mutagenesis in soybean using the CRISPR-Cas9 system. Sci Rep 5:10342PubMedPubMedCentralCrossRefGoogle Scholar
  97. Taura F (2009) Studies on tetrahydrocannabinolic acid synthase that produces the acidic precursor of tetrahydrocannabinol, the pharmacologically active cannabinoid in marijuana. Drug Discov Ther 3:83–87Google Scholar
  98. Taura F, Dono E, Sirikantaramas S, Yoshimura K, Shoyama Y, Morimoto S (2007) Production of Δ1-tetrahydrocannabinolic acid by the biosynthetic enzyme secreted from transgenic Pichia pastoris. Biochem Bioph Res Co 361:675–680CrossRefGoogle Scholar
  99. Taura F, Morimoto S, Shoyama Y, Mechoulam R (1995) First direct evidence for the mechanism of Δ1-tetrahydrocannabinolic acid biosynthesis. J Am Chem Soc 117:9766–9767CrossRefGoogle Scholar
  100. Taura F, Tanaka S, Taguchi C, Fukamizu T, Tanaka H, Shoyama Y, Morimoto S (2009) Characterization of olivetol synthase, a polyketide synthase putatively involved in cannabinoid biosynthetic pathway. FEBS Lett 583:2061–2066PubMedCrossRefGoogle Scholar
  101. Tepfer D (1990) Genetic transformation using Agrobacterium rhizogenes. Physiol Plantarum 79:140–146CrossRefGoogle Scholar
  102. van Bakel H, Stout JM, Cote AG, Tallon CM, Sharpe AG, Hughes TR, Page JE (2011) The draft genome and transcriptome of Cannabis sativa. Genome Biol 12:R102PubMedPubMedCentralCrossRefGoogle Scholar
  103. van den Broeck HC, Maliepaard C, Ebskamp MJM, Toonen MAJ, Koops AJ (2008) Differential expression of genes involved in C1 metabolism and lignin biosynthesis in wooden core and bast tissues of fibre hemp (Cannabis sativa L.). Plant Sci 174:205–220CrossRefGoogle Scholar
  104. Veena V, Taylor CG (2007) Agrobacterium rhizogenes: recent developments and promising applications. In Vitro Cell Dev Biol Plant 43:383–403CrossRefGoogle Scholar
  105. Velasco G, Sánchez C, Guzmán M (2012) Towards the use of cannabinoids as antitumor agents. Nat Rev Cancer 12:436–444PubMedCrossRefGoogle Scholar
  106. Wahby I, Caba JM, Ligero F (2012) Agrobacterium infection of hemp (Cannabis sativa L.): establishment of hairy root cultures. J Plant Interact 8:312–320CrossRefGoogle Scholar
  107. Wang R, He L-S, Xia B, Tong J-F, Li N, Peng F (2009) A micropropagation system for cloning of hemp (Cannabis sativa L.) by shoot tip culture. Pak J Bot 41:603–608Google Scholar
  108. Weiblen GD, Wenger JP, Craft KJ, ElSohly MA, Mehmedic Z, Treiber EL, Marks MD (2015) Gene duplication and divergence affecting drug content in Cannabis sativa. New Phytol 208:1241–1250PubMedCrossRefGoogle Scholar
  109. Wroblewski T, Tomczak A, Michelmore R (2005) Optimization of Agrobacterium-mediated transient assays of gene expression in lettuce, tomato and Arabidopsis. Plant Biotechnol J 3:259–273PubMedCrossRefGoogle Scholar
  110. Zaenen I, van Larebeke N, Teuchy H, van Montagu M, Schell J (1974) Supercoiled circular DNA in crown-gall inducing Agrobacterium strains. J Mol Biol 86:109–127PubMedCrossRefGoogle Scholar
  111. Zhang L, Ding R, Chai Y, Bonfill M, Moyano E, Oksman-Caldentey KM, Xu T, Pi Y, Wang Z, Zhang H, Kai G, Liao Z, Sun X, Tang K (2004) Engineering tropane biosynthetic pathway in Hyoscyamus niger hairy root cultures. Proc Nat Acad Sci 101:6786–6791PubMedPubMedCentralCrossRefGoogle Scholar
  112. Zirpel B, Stehle F, Kayser O (2015) Production of Δ9-tetrahydrocannabinolic acid from cannabigerolic acid by whole cells of Pichia (Komagataella) pastoris expressing Δ9-tetrahydrocannabinolic acid synthase from Cannabis sativa L. Biotechnol Lett 37:1869–1875PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.School of Life SciencesUniversity of WarwickCoventryUK
  2. 2.Department of Biological Sciences, Plant Pathology and BiotechnologySimon Fraser UniversityBurnabyCanada

Personalised recommendations