PRODUCTION OF CANNABINOIDS BY BIOTECHNOLOGICAL METHODS INCLUDING SYNTHETIC BIOLOGY
Abstract views: 111 / PDF downloads: 29Keywords:
Cannabis, secondary metabolite, metabolic engineering, gene editing, biotechnologyAbstract
Cannabis is probably the best known species for the production of alkaloids of medical importance. Recent biotechnological approaches lead to the utilization of biotechnological methods, including metabolic engineering and synthetic biology to increase the productivity of cannabis secondary metabolites with medical importance and economic value. Hence, this review article presents the biosynthetic pathway of cannabinoid biosynthesis to underline the important genes that could be used for enhancement of cannabinoid production together with a summary of studies of biotechnological technologies including in vitro culture, polyploidy induction, gene transformation, gene editing, metabolic engineering, and synthetic biology used in cannabis.
References
Gloss D. (2015). An Overview of Products and Bias in Research. Neurotherapeutics, 12(4): 731-4.
Lazarjani, M. P., Young, O., Kebede, L. Seyfoddin, A. 2021. Processing and extraction methods of medicinal cannabis: a narrative review. J Cannabis Res, 3: 32.
Andre, C.M., Hausman, J.F., and Guerriero, G. (2016). Cannabis sativa: the plant of the thousand and one molecules. Front. Plant Sci, 7: 19.
Hill, A.J., Williams, C.M., Whalley, B.J., and Stephens, G.J. (2012). Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther, 133: 79-97.
Jung, B., Lee, J.K., Kim, J., Kang, E.K., Han, S.Y., Lee, H.Y., Choi, I.S. (2019). Synthetic Strategies for (-)-Cannabidiol and Its Structural Analogs. Chem Asian J, 14(21): 3749-3762.
Luo, X., Reiter, M.A., d’Espaux, L., Wong, J., Denby, C.M., Lechner, A., Zhang, Y., Grzybowski, A.T., Harth, S., Lin, W., Lee, H., Yu, C., Shin, J., Deng, K., Benites, V.T., Wang, G., Baidoo, E.K., Chen, Y., Dev, I., Petzold, C.J., Keasling, J.D. (2019): Complete biosynthesis of cannabinoids and their unnatural analogues in yeast. Nature, 567: 123-126.
Blake, A., Nahtigal, I. (2019). The evolving landscape of cannabis edibles. Current Opinion in Food Science, 28: 25-31. ISSN 2214-7993.
Testai, F. D., Gorelick, P. B., Aparicio, H. J., Filbey, F. M., Gonzalez, R., Gottesman, R. F., Melis, M., Piano, M. R., Rubino, T., Song, S. Y. (2022). Use of marijuana: effect on brain health: a scientific statement from the American Heart Association. Stroke, 53(4): 176-187.
Citti, C., Braghiroli, D., Vandelli, M. A., Cannazza, G. (2018). Pharmaceutical and biomedical analysis of cannabinoids: A critical review. J Pharm Biomed Anal, 147: 565-579.
Gülck, T., Møller, B. L. (2020). Phytocannabinoids: origins and biosynthesis. Trends Plant Sci, 25: 985-1004.
Bilodeau, S. E., Wu, B.-S., Rufyikiri, A.-S., MacPherson, S., Lefsrud, M. 2(019). An update on plant photobiology and implications for cannabis production. Front Plant Sci, 10: 296.
Govindarajan, R. K., Mishra, A. K., Cho, K.-H., Kim, K.-H., Yoon, K. M., Baek, K.-H. (2023). Biosynthesis of Phytocannabinoids and Structural Insights: A Review. Metabolites, 13: 442.
Hanuš, L. O., Meyer, S. M., Muñoz, E., Taglialatela-Scafati, O., Appendino, G. (2016). Phytocannabinoids: a unified critical inventory. Nat Prod Rep, 33: 1357-1392.
Livingston, S. J., Quilichini, T. D., Booth, J. K., Wong, D. C. J., Rensing, K. H., Laflamme-Yonkman, J., Castellarin, S. D., Bohlmann, J., Page, J. E., Samuels, A. L. (2020). Cannabis glandular trichomes alter morphology and metabolite content during flower maturation. Plant J, 101(1): 37-56.
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: 1578-1582.
Degenhardt, F., Stehle, F., Kayser, O. (2017). The biosynthesis of cannabinoids. In Handbook of Cannabis and Related Pathologies; Elsevier: Amsterdam, The Netherlands, pp. 13-23.
Fellermeier M, Eisenreich W, Bacher A, Zenk MH. (2001). Biosynthesis of cannabinoids. Incorporation experiments with (13)C-labeled glucoses. Eur J Biochem, 268: 1596-1604.
Rodziewicz, P., Loroch, S., Marczak, Ł., Sickmann, A., Kayser, O. (2019). Cannabinoid synthases and osmoprotective metabolites accumulate in the exudates of Cannabis sativa L. glandular trichomes. Plant Sci, 284: 108-116.
Geissler, M., Volk, J., Stehle, F., Kayser, O., Warzecha, H. (2018). Subcellular localization defines modification and production of Δ9-tetrahydrocannabinolic acid synthase in transiently transformed Nicotiana benthamiana. Biotechnol Lett, 40: 981-987.
Stout, J. M., Boubakir, Z., Ambrose, S. J., Purves, R. W., Page, J. E. (2012). The hexanoyl‐CoA precursor for cannabinoid biosynthesis is formed by an acyl‐activating enzyme in Cannabis sativa trichomes. The Plant Journal, 71(3): 353-365.
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(12): 2061-6.
Gagne, S., Stout, J., Liu, E., Boubakir, Z., Clark, S. and Page, J. (2012). Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proceedings of the National Academy of Sciences, 109(31): 12811-12816.
Laverty, K. U., Stout, J. M., Sullivan, M. J., Shah, H., Gill, N., Holbrook, L., Deikus, G., Sebra, R., Hughes, T. R., Page, J. E., van Bakel, H. (2019). A physical and genetic map of Cannabis sativa identifies extensive rearrangements at the THC/CBD acid synthase loci. Genome Res, 29(1): 146-156.
Iijima, M., Munakata, R., Takahashi, H., Kenmoku, H., Nakagawa, R., Kodama, T., Asakawa, Y., Abe, I., Yazaki, K., Kurosaki, F., Taura, F. (2017). Identification and Characterization of Daurichromenic Acid Synthase Active in Anti-HIV Biosynthesis. Plant Physiol, 174(4): 2213-2230.
Thakur, G. A., Duclos, R. I. Jr., Makriyannis, A. (2005). Natural cannabinoids: templates for drug discovery. Life Sci, 78(5): 454-66.
Valliere, M. A., Korman, T. P., Woodall, N. B. et al. (2019). A cell-free platform for the prenylation of natural products and application to cannabinoid production. Nat Commun, 10: 565.
Anand, U., Pacchetti, B., Anand, P., Sodergren, M. H. (2021). Cannabis-based medicines and pain: A review of potential synergistic and entourage effects. Pain Manag, 11: 395-403.
de Meijer, E. P. M., Bagatta, M., Carboni, A., Crucitti, P., Moliterni, V. M., Ranalli, P., Mandolino, G. (2003). The inheritance of chemical phenotype in Cannabis sativa L. Genetics, 163(1): 335-46.
Van Bakel, H., Stout J. M., Cote, A. G., Tallon, C. M., Sharpe, A. G., Hughes, T. R., Page, J. E. (2011). The draft genome and transcriptome of Cannabis sativa. Genome Biol, 12: R102.
Onofri, C., de Meijer, E. P. M., Mandolino, G. (2015). Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype. Phytochemistry, 116: 57-68.
Weiblen, G. D., Wenger, J. P., Craft, K. J., ElSohly, M. A., Mehmedic, Z., Treiber, E. L., Marks, M. D. (2015). Gene duplication and divergence affecting drug content in Cannabis sativa. New Phytol, 208: 1241-1250.
Grassa, C. J., Weiblen, G. D., Wenger, J. P., Dabney, C., Poplawski, S. G., Timothy Motley, S., Michael., T.P., Schwartz, C.J. (2021). A new Cannabis genome assembly associates elevated cannabidiol (CBD) with hemp introgressed into marijuana. New Phytol, 230(4): 1665-79.
Vergara, D., Huscher, E. L., Keepers, K. G., Givens, R. M., Cizek, C. G., Torres, A., et al. (2019). Gene copy number is associated with phytochemistry in Cannabis sativa. AoB PLANTS, 11(6).
Iranbakhsh, A., Oraghi Ardebili, Z., Molaei, H., Oraghi Ardebili, N., Amini, M. (2020). Cold plasma up-regulated expressions of WRKY1 transcription factor and genes involved in biosynthesis of cannabinoids in Hemp (Cannabis sativa L.). Plasma Chemistry and Plasma Processing, 40: 527-537.
Apicella, P. V., Sands, L. B., Ma, Y., Berkowitz, G. A. (2022). Delineating genetic regulation of cannabinoid biosynthesis during female flower development in Cannabis sativa. Plant Direct, 6(6): 412.
MacKinnon, L., McDougall, G., Aziz, N., Millam, S. (2000). Progress towards transformation of fibre hemp. Annu Rep Scott Crop Res Inst, 18: 84-86.
Feeney, M., Punja, Z. K. (2003). Tissue culture and Agrobacterium-mediated transformation of hemp (Cannabis sativa L.). Vitr. Cell. Dev. Biol. Plant, 39: 578-585.
Wahby, I., Caba, J. M., Ligero, F. (2013). Agrobacterium infection of hemp (Cannabis sativa L.): Establishment of hairy root cultures. J. Plant. Interact, 8: 312-320.
Niazian, M. (2019). Application of genetics and biotechnology for improving medicinal plants. Planta, 249(4): 953-973.
Morimoto, S., Tanaka, Y., Sasaki, K., Tanaka, H., Fukamizu, T., Shoyama, Y., Shoyama, Y., Taura, F. (2007). Identification and characterization of cannabinoids that induce cell death through mitochondrial permeability transition in Cannabis leaf cells. J Biol Chem, 282(28): 20739-51.
Beard, K. M., Boling, A. W. H., Bargmann, B. O. R. (2021). Protoplast isolation, transient transformation, and flow-cytometric analysis of reporter-gene activation in Cannabis sativa L. Ind Crop Prod, 164: 13360.
Deguchi, M., Bogush, D., Weeden, H., Spuhler, Z., Potlakayala, S., Kondo, T., Zhang, Z. J., Rudrabhatla, S. (2020). Establishment and optimization of a hemp (Cannabis sativa L.) agroinfiltration system for gene expression and silencing studies. Sci Rep, 10: 3504.
Sorokin, A., Yadav, N. S., Gaudet, D., Kovalchuk, I. (2020). Transient expression of the β-glucuronidase gene in Cannabis sativa varieties. Plant Signal Behav, 15: 1780037.
Zhang, X., Xu, G., Cheng, C., Lei, L., Sun, J., Xu, Y., Deng, C., Dai, Z., Yang, Z., Chen, X., Liu, C., Tang, Q., Su, J. (2021). Establishment of an Agrobacterium-mediated genetic transformation and CRISPR/Cas9-mediated targeted mutagenesis in Hemp (Cannabis sativa L.). Plant Biotechnol J, 19(10): 1979-1987.
Gündoğdu, R., Çelik, V. (2009). RNA İNTERFERANS (RNAi). Erciyes University Journal of the Institute of Science and Technology, 25: 34-47.
Matchett-Oates, L., Spangenberg, G. C. and Cogan, N. O. I. (2021). Manipulation of Cannabinoid Biosynthesis via Transient RNAi Expression. Front Plant Sci, 12: 773474.
Schachtsiek, J., Hussain, T., Azzouhri, K., Kayser, O., Stehle, F. (2019). Virus-induced gene silencing (VIGS) in Cannabis sativa L.. Plant Methods, 15: 157.
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: 1869-1875.
Taura, F., Sirikantaramas, S., Shoyama, Y., Yoshikai, K., Shoyama, Y., Morimoto, S. (2007). Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa. FEBS Lett, 581(16): 2929-2934.
Small, E. (2017). Cannabis Chemistry: Cannabinoids in Cannabis, Humans, and Other Species In: Cannabis, A complete guide, Boca Raton: Taylor & Francis, Chapter 11: 199-220.
Walsh, K. B., McKinney, A. E., Holmes, A. E. (2021). Minor Cannabinoids: Biosynthesis, Molecular Pharmacology and Potential Therapeutic Uses. Front Pharmacol, 12: 777804.
Grassi, G., McPartland, J. M. (2017). Chemical and Morphological Phenotypes in Breeding of Cannabis sativa L.. In: Chandra, S., Lata, H., ElSohly, M. (eds) Cannabis sativa L. Botany and Biotechnology, Springer, Cham.
Mansouri, H., Bagheri, M. (2017). Induction of Polyploidy and Its Effect on Cannabis sativa L.. In: Chandra, S., Lata, H., ElSohly, M. (eds) Cannabis sativa L. Botany and Biotechnology, Springer, Cham.
Salma, U., Kundu, S., Mandal, N. (2017). Artificial polyploidy in medicinal plants: Advancement in the last two decades and impending prospects. J Crop Sci Biotechnol, 20: 9-19.
Pradhan, S. K., Gupta, R. C., Goel, R. K. (2018). Differential content of secondary metabolites in diploid and tetraploid cytotypes of Siegesbeckia orientalis L., Natural Product Research, 32(20): 2476-248
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Türk Bilimsel Derlemeler Dergisi
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
