Recent advances towards development and commercialization of plant cell culture processes for the synthesis of biomolecules
Summary
Plant cell culture systems were initially explored for use in commercial synthesis of several high‐value secondary metabolites, allowing for sustainable production that was not limited by the low yields associated with natural harvest or the high cost associated with complex chemical synthesis. Although there have been some commercial successes, most notably paclitaxel production from Taxus sp., process limitations exist with regards to low product yields and inherent production variability. A variety of strategies are being developed to overcome these limitations including elicitation, in situ product removal and metabolic engineering with single genes and transcription factors. Recently, the plant cell culture production platform has been extended to pharmaceutically active heterologous proteins. Plant systems are beneficial because they are able to produce complex proteins that are properly glycosylated, folded and assembled without the risk of contamination by toxins that are associated with mammalian or microbial production systems. Additionally, plant cell culture isolates transgenic material from the environment, allows for more controllable conditions over field‐grown crops and promotes secretion of proteins to the medium, reducing downstream purification costs. Despite these benefits, the increase in cost of heterologous protein synthesis in plant cell culture as opposed to field‐grown crops is significant and therefore processes must be optimized with regard to maximizing secretion and enhancing protein stability in the cell culture media. This review discusses recent advancements in plant cell culture processing technology, focusing on progress towards overcoming the problems associated with commercialization of these production systems and highlighting recent commercial successes.
Number of times cited: 98
- Chelsea Dixon, Lisa R. Wilken, Susan L. Woodard and Georgia O.F. Barros, The Impact of Six Critical Impurities on Recombinant Protein Recovery and Purification from Plant Hosts, Molecular Pharming, (137-180), (2018).
- Fei Qiao, Xue-fei Jiang, Han-qing Cong, Hua-peng Sun, Li Li and Peter Nick, Cell shape can be uncoupled from formononetin induction in a novel cell line from Callerya speciosa, Plant Cell Reports, (2018).
- Guy Polturak and Asaph Aharoni, “La Vie en Rose”: Biosynthesis, Sources, and Applications of Betalain Pigments, Molecular Plant, 11, 1, (7), (2018).
- Julie A. Himmelberger, Kathryn E. Cole and Daniel P. Dowling, Biocatalysis, Green Chemistry, 10.1016/B978-0-12-809270-5.00019-4, (471-512), (2018).
- Jae Kook Lee, Seung Hee Eom and Tae Kyung Hyun, Enhanced biosynthesis of saponins by coronatine in cell suspension culture of Kalopanax septemlobus, 3 Biotech, 8, 1, (2018).
- Christopher McElroy and Stefan Jennewein, Taxol® Biosynthesis and Production: From Forests to Fermenters, Biotechnology of Natural Products, 10.1007/978-3-319-67903-7_7, (145-185), (2017).
- J.F. Buyel, Plants as sources of natural and recombinant anti-cancer agents, Biotechnology Advances, 10.1016/j.biotechadv.2018.02.002, 36, 2, (506-520), (2018).
- Sarah A. Wilson, Patricia Keen, Michelle C. McKee, Nicole Raia, Joyce Van Eck and Susan C. Roberts, Development of an Agrobacterium-mediated transformation method for Taxus suspension cultures, In Vitro Cellular & Developmental Biology - Plant, 54, 1, (36), (2018).
- Bernd Markus Lange, Commercial-Scale Tissue Culture for the Production of Plant Natural Products: Successes, Failures and Outlook, Biotechnology of Natural Products, 10.1007/978-3-319-67903-7_8, (189-218), (2017).
- Tiago Fidemann, Gabriela Aparecida de Araujo Pereira, Tárik Reis Heluy, Rodrigo Boccoli Gallego, Mônica Rosa Bertão, Regildo Márcio Gonçalves da Silva and Eutimio Gustavo Fernández Núñez, Handling culture medium composition for optimizing plant cell suspension culture in shake flasks, Plant Cell, Tissue and Organ Culture (PCTOC), (2017).
- Simón Villegas-Velásquez, Anny D. Martínez-Mira, Rodrigo Hoyos, Benjamín Rojano and Fernando Orozco-Sánchez, Hydrodynamic stress and limonoid production in Azadirachta indica cell culture, Biochemical Engineering Journal, 10.1016/j.bej.2017.03.004, 122, (75-84), (2017).
- Fatemeh Rajabi, Ernst Heene, Jan Maisch, Peter Nick and Gabriel Agbor, Combination of Plant Metabolic Modules Yields Synthetic Synergies, PLOS ONE, 12, 1, (e0169778), (2017).
- Sushma Chityala, Vidhyadhar Nandana, Dharanidaran Jayachandran, Ashish A. Prabhu and Veeranki Venkata Dasu, Biotechnology of Commercial Microbial Products, Plant-Microbe Interactions in Agro-Ecological Perspectives, 10.1007/978-981-10-6593-4_21, (521-542), (2017).
- Amol Sarkate, Somesh Banerjee, Javid Iqbal Mir, Partha Roy and Debabrata Sircar, Antioxidant and cytotoxic activity of bioactive phenolic metabolites isolated from the yeast-extract treated cell culture of apple, Plant Cell, Tissue and Organ Culture (PCTOC), 130, 3, (641), (2017).
- Jae-Wan Jung, Nguyen-Xuan Huy, Hyo-Boon Kim, Nan-Sun Kim, Do Van Giap and Moon-Sik Yang, Production of recombinant human acid α-glucosidase with high-mannose glycans in gnt1 rice for the treatment of Pompe disease, Journal of Biotechnology, 249, (42), (2017).
- Dinesh Chandra Agrawal, Emily Chin-Fun Chen, Hung-Chi Chang, Chia-Chen Chen, Chao-Lin Kuo and Hsin-Sheng Tsay, Biotechnology of Medicinal Plants and Fungi in Taiwan: Production of Bioactive Secondary Metabolites in In Vitro Culture Systems, Medicinal Plants and Fungi: Recent Advances in Research and Development, 10.1007/978-981-10-5978-0_14, (459-483), (2017).
- Mariam Gaid, Thomas Wucherpfennig, Stephan Scholl, Ludger Beerhues and Rainer Krull, Challenges for the Cultivation of Plant Cells on the Example of Hypericum Perforatum and Taxus Chinensis, Bioprocessing of Plant In Vitro Systems, 10.1007/978-3-319-32004-5_13-1, (1-26), (2017).
- Dipasree Roychowdhury, Mihir Halder and Sumita Jha, Agrobacterium rhizogenes-Mediated Transformation in Medicinal Plants: Genetic Stability in Long-Term Culture, Transgenesis and Secondary Metabolism, 10.1007/978-3-319-28669-3_8, (323-345), (2017).
- A. Marchev and M. Georgiev, Plant Cell Bioprocesses, Current Developments in Biotechnology and Bioengineering, 10.1016/B978-0-444-63663-8.00004-5, (73-95), (2017).
- Mariam Gaid, Eline Biedermann, Jendrik Füller, Paul Haas, Sönke Behrends, Rainer Krull, Stephan Scholl, Ute Wittstock, Christel Müller-Goymann and Ludger Beerhues, Biotechnological production of hyperforin for pharmaceutical formulation, European Journal of Pharmaceutics and Biopharmaceutics, 10.1016/j.ejpb.2017.03.024, (2017).
- Liudmila Korkina, Wolfgang Mayer and Chiara de Luca, Meristem Plant Cells as a Sustainable Source of Redox Actives for Skin Rejuvenation, Biomolecules, 7, 2, (40), (2017).
- Diego Hidalgo, Maryam Abdoli -Nasab, Mokhtar Jalali-Javaran, Roque Bru-Martínez, Rosa M. Cusidó, Purificación Corchete and Javier Palazon, Biotechnological production of recombinant tissue plasminogen activator protein (reteplase) from transplastomic tobacco cell cultures, Plant Physiology and Biochemistry, 10.1016/j.plaphy.2017.06.013, 118, (130-137), (2017).
- Dubravko Pavoković, Renata Buđa, Fran Andrašec, Marin Roje, Marina Cvjetko Bubalo and Ivana Radojčić Redovniković, Plant-mediated asymmetric reduction of 1-(3,4-dimethylphenyl)ethanone, Tetrahedron: Asymmetry, 10.1016/j.tetasy.2017.04.003, 28, 5, (730-733), (2017).
- B. Grout, General Principles of Tissue Culture, Encyclopedia of Applied Plant Sciences, 10.1016/B978-0-12-394807-6.00143-X, (437-443), (2017).
- Peyman Habibi, Maria Fatima Grossi De Sa, Abdullah Makhzoum, Sonia Malik, André Luís Lopes da Silva, Kathleen Hefferon and Carlos Ricardo Soccol, Bioengineering Hairy Roots: Phytoremediation, Secondary Metabolism, Molecular Pharming, Plant-Plant Interactions and Biofuels, Sustainable Agriculture Reviews, 10.1007/978-3-319-48006-0_7, (213-251), (2017).
- Julia Seidel, Tilman Ahlfeld, Max Adolph, Sibylle Kümmritz, Juliane Steingroewer, Felix Krujatz, Thomas Bley, Michael Gelinsky and Anja Lode, Green bioprinting: extrusion-based fabrication of plant cell-laden biopolymer hydrogel scaffolds, Biofabrication, 9, 4, (045011), (2017).
- Gregory R. Andrews and Susan C. Roberts, Bioprocess Engineering of Plant Cell Suspension Cultures, Applied Bioengineering, (283-326), (2017).
- Verity I. P. Loake and Marisol Ochoa-Villarreal, Cambial Meristematic Cells: A Sustainable Platform for the Production of Plant-Derived Anticancer Drugs, Biotechnology and Production of Anti-Cancer Compounds, 10.1007/978-3-319-53880-8_6, (143-156), (2017).
- Diego Hidalgo, Milen Georgiev, Andrey Marchev, Roque Bru-Martínez, Rosa M. Cusido, Purificación Corchete and Javier Palazon, Tailoring tobacco hairy root metabolism for the production of stilbenes, Scientific Reports, 10.1038/s41598-017-18330-w, 7, 1, (2017).
- J. F. Buyel, How Plants Can Contribute to the Supply of Anticancer Compounds, Biotechnology and Production of Anti-Cancer Compounds, 10.1007/978-3-319-53880-8_2, (39-72), (2017).
- Adriana Villegas, Juan Pablo Arias, Daira Aragón, Silvia Ochoa and Mario Arias, First principle-based models in plant suspension cell cultures: a review, Critical Reviews in Biotechnology, 10.1080/07388551.2017.1304891, 37, 8, (1077-1089), (2017).
- Le Zhao, Zengyi Shao and Jacqueline V Shanks, Anticancer Drugs, Industrial Biotechnology, (237-269), (2016).
- Johan Andersen‐Ranberg, Kenneth Thermann Kongstad, Morten Thrane Nielsen, Niels Bjerg Jensen, Irini Pateraki, Søren Spanner Bach, Britta Hamberger, Philipp Zerbe, Dan Staerk, Jörg Bohlmann, Birger Lindberg Møller and Björn Hamberger, Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis, Angewandte Chemie International Edition, 55, 6, (2142-2146), (2016).
- Johan Andersen‐Ranberg, Kenneth Thermann Kongstad, Morten Thrane Nielsen, Niels Bjerg Jensen, Irini Pateraki, Søren Spanner Bach, Britta Hamberger, Philipp Zerbe, Dan Staerk, Jörg Bohlmann, Birger Lindberg Møller and Björn Hamberger, Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis, Angewandte Chemie, 128, 6, (2182-2186), (2016).
- Yan‐shan Dong, Chun‐hua Fu, Peng Su, Xiang‐ping Xu, Jie Yuan, Sheng Wang, Meng Zhang, Chun‐fang Zhao and Long‐jiang Yu, Mechanisms and effective control of physiological browning phenomena in plant cell cultures, Physiologia Plantarum, 156, 1, (13-28), (2015).
- Andrew Diamond and Isabel Desgagné‐Penix, Metabolic engineering for the production of plant isoquinoline alkaloids, Plant Biotechnology Journal, 14, 6, (1319-1328), (2015).
- Wanxia Xia, Lei Lei, Wei Zhao, Yifan Feng and Shujin Zhao, Quantitative analysis of 2,3,5,4′-tetrahydroxystilbene-2-O-β-d-glycoside in wild Polygonum multiflorum and suspension cell cultures fed different precursors and elicitors, Phytochemistry Letters, 15, (180), (2016).
- Dipasree Roychowdhury, Mihir Halder and Sumita Jha, Agrobacterium rhizogenes-Mediated Transformation in Medicinal Plants: Genetic Stability in Long-Term Culture, Transgenesis and Secondary Metabolism, 10.1007/978-3-319-27490-4_8-1, (1-23), (2016).
- Ningning Zhang, Maureen Dolan, Di Wu, Gregory C. Phillips and Jianfeng Xu, Dramatic secretion of recombinant protein expressed in tobacco cells with a designer glycopeptide tag is highly impacted by medium composition, Plant Cell Reports, 10.1007/s00299-016-2051-6, 35, 12, (2513-2522), (2016).
- Mariela J. Simão, Eduardo Fonseca, Renata Garcia, Elisabeth Mansur and Georgia Pacheco, Effects of auxins and different culture systems on the adventitious root development of Passiflora pohlii Mast. and their ability to produce antioxidant compounds, Plant Cell, Tissue and Organ Culture (PCTOC), 124, 2, (419), (2016).
- Georgia Pacheco, Mariela J. Simão, Marcela G. Vianna, Renata O. Garcia, Maria Lucia C. Vieira and Elisabeth Mansur, In vitro conservation of Passiflora —A review, Scientia Horticulturae, 211, (305), (2016).
- Jae-Wan Jung, Nan-Sun Kim, Seon-Hui Jang, Yun-Ji Shin and Moon-Sik Yang, Production and characterization of recombinant human acid α-glucosidase in transgenic rice cell suspension culture, Journal of Biotechnology, 226, (44), (2016).
- S. Deepthi and K. Satheeshkumar, Enhanced camptothecin production induced by elicitors in the cell suspension cultures of Ophiorrhiza mungos Linn., Plant Cell, Tissue and Organ Culture (PCTOC), 124, 3, (483), (2016).
- Marisol Ochoa-Villarreal, Susan Howat, SunMi Hong, Mi Ok Jang, Young-Woo Jin, Eun-Kyong Lee and Gary J. Loake, Plant cell culture strategies for the production of natural products, BMB Reports, 10.5483/BMBRep.2016.49.3.264, 49, 3, (149-158), (2016).
- , Industrial Production of Nanonutraceuticals, Nanotechnology in Nutraceuticals, 10.1201/9781315370859-15, (275-287), (2016).
- Jianfeng Xu, Melissa Towler and Pamela J. Weathers, Platforms for Plant-Based Protein Production, Bioprocessing of Plant In Vitro Systems, 10.1007/978-3-319-32004-5_14-1, (1-40), (2016).
- Ze-Jian Wang, Wei Zhang, Jian-Wen Zhang, Mei-Jin Guo and Ying-ping Zhuang, Optimization of a broth conductivity controlling strategy directed by an online viable biomass sensor for enhancing Taxus cell growth rate and Taxol productivity, RSC Advances, 10.1039/C5RA26540A, 6, 47, (40631-40640), (2016).
- Qing-Yan Gai, Jiao Jiao, Meng Luo, Wei Wang, Cheng-Bo Gu, Yu-Jie Fu and Wei Ma, Tremendous enhancements of isoflavonoid biosynthesis, associated gene expression and antioxidant capacity in Astragalus membranaceus hairy root cultures elicited by methyl jasmonate, Process Biochemistry, 51, 5, (642), (2016).
- Martin Heining and Rainer Buchholz, Photobioreactors with internal illumination – A survey and comparison, Biotechnology Journal, 10, 8, (1131-1137), (2015).
- Shinjiro Yamamoto, Shuhei Hayashi, Shintaro Furusaki and Suteaki Shioya, 5‐Aminolevulinic acid promotes callus growth and paclitaxel production in light‐grown Taxus cuspidata suspension cultures, Engineering in Life Sciences, 15, 1, (116-121), (2014).
- Da Cheng Hao, Xiao-Jie Gu and Pei Gen Xiao, Taxus medicinal resources, Medicinal Plants, 10.1016/B978-0-08-100085-4.00003-7, (97-136), (2015).
- Aarthi Venugopalan and Smita Srivastava, Endophytes as in vitro production platforms of high value plant secondary metabolites, Biotechnology Advances, 33, 6, (873), (2015).
- Marisol Ochoa-Villarreal, Susan Howat, Mi Ok Jang, Il Suk Kim, Young-Woo Jin, Eun-Kyong Lee and Gary J. Loake, Cambial meristematic cells: a platform for the production of plant natural products, New Biotechnology, 10.1016/j.nbt.2015.02.003, 32, 6, (581-587), (2015).
- S. M. M. R. Mawalagedera and Kevin S. Gould, Chilling and salinity increase extractable antioxidants in cell suspension cultures of the sow thistle, Sonchus oleraceus L., Plant Cell, Tissue and Organ Culture (PCTOC), 121, 1, (35), (2015).
- Najla Chalbi, Mª Carmen Martínez-Ballesta, Nabil Ben Youssef and Micaela Carvajal, Intrinsic stability of Brassicaceae plasma membrane in relation to changes in proteins and lipids as a response to salinity, Journal of Plant Physiology, 175, (148), (2015).
- Kristian K Ullrich, Manuel Hiss and Stefan A Rensing, Means to optimize protein expression in transgenic plants, Current Opinion in Biotechnology, 10.1016/j.copbio.2014.11.011, 32, (61-67), (2015).
- J.F. Buyel, R.M. Twyman and R. Fischer, Extraction and downstream processing of plant-derived recombinant proteins, Biotechnology Advances, 10.1016/j.biotechadv.2015.04.010, 33, 6, (902-913), (2015).
- Adriana Silva da Rocha, Emely Kazan Rocha, Luciano Marques Alves, Brenda Amaral de Moraes, Tatiana Carvalho de Castro, Norma Albarello and Claudia Simões-Gurgel, Production and optimization through elicitation of carotenoid pigments in the in vitro cultures of Cleome rosea Vahl (Cleomaceae), Journal of Plant Biochemistry and Biotechnology, 24, 1, (105), (2015).
- Atanas G. Atanasov, Birgit Waltenberger, Eva-Maria Pferschy-Wenzig, Thomas Linder, Christoph Wawrosch, Pavel Uhrin, Veronika Temml, Limei Wang, Stefan Schwaiger, Elke H. Heiss, Judith M. Rollinger, Daniela Schuster, Johannes M. Breuss, Valery Bochkov, Marko D. Mihovilovic, Brigitte Kopp, Rudolf Bauer, Verena M. Dirsch and Hermann Stuppner, Discovery and resupply of pharmacologically active plant-derived natural products: A review, Biotechnology Advances, 10.1016/j.biotechadv.2015.08.001, 33, 8, (1582-1614), (2015).
- Rainer Fischer, Nikolay Vasilev, Richard M Twyman and Stefan Schillberg, High-value products from plants: the challenges of process optimization, Current Opinion in Biotechnology, 10.1016/j.copbio.2014.12.018, 32, (156-162), (2015).
- Yanshan Dong, Wenlan Duan, Huixia He, Peng Su, Meng Zhang, Guanghao Song, Chunhua Fu and Longjiang Yu, Enhancing taxane biosynthesis in cell suspension culture of Taxus chinensis by overexpressing the neutral/alkaline invertase gene, Process Biochemistry, 50, 4, (651), (2015).
- Philipp Zerbe and Jörg Bohlmann, Plant diterpene synthases: exploring modularity and metabolic diversity for bioengineering, Trends in Biotechnology, 10.1016/j.tibtech.2015.04.006, 33, 7, (419-428), (2015).
- Lidiya Georgieva, Ivan Ivanov, Andrey Marchev, Ina Aneva, Panteley Denev, Vasil Georgiev and Atanas Pavlov, Protopine Production by Fumaria Cell Suspension Cultures: Effect of Light, Applied Biochemistry and Biotechnology, 176, 1, (287), (2015).
- Anastasia Krivoruchko and Jens Nielsen, Production of natural products through metabolic engineering of Saccharomyces cerevisiae, Current Opinion in Biotechnology, 10.1016/j.copbio.2014.12.004, 35, (7-15), (2015).
- Nicole Imseng, Stefan Schillberg, Cornelia Schürch, Daniel Schmid, Kai Schütte, Gilbert Gorr, Dieter Eibl and Regine Eibl, Suspension Culture of Plant Cells Under Heterotrophic Conditions, Industrial Scale Suspension Culture of Living Cells, (224-258), (2014).
- Liisa Nohynek, Michael Bailey, Juha Tähtiharju, Tuulikki Seppänen‐Laakso, Heiko Rischer, Kirsi‐Marja Oksman‐Caldentey and Riitta Puupponen‐Pimiä, Cloudberry (Rubus chamaemorus) cell culture with bioactive substances: Establishment and mass propagation for industrial use, Engineering in Life Sciences, 14, 6, (667-675), (2014).
- Sören Werner, Judith Greulich, Katja Geipel, Juliane Steingroewer, Thomas Bley and Dieter Eibl, Mass propagation of Helianthus annuus suspension cells in orbitally shaken bioreactors: Improved growth rate in single‐use bag bioreactors, Engineering in Life Sciences, 14, 6, (676-684), (2014).
- Edgar García López, Emma Gloria Ramos Ramírez, Octavio Gómez Gúzman, Graciano Calva Calva, Armando Ariza‐Castolo, Josefina Pérez‐Vargas and Herminia Guadalupe Martínez Rodríguez, MALDI‐TOF characterization of hGH1 produced by hairy root cultures of Brassica oleracea var. italica grown in an airlift with mesh bioreactor, Biotechnology Progress, 30, 1, (161-171), (2013). 2014 40th Annual Northeast Bioengineering Conference (NEBEC) Boston, MA, USA 2014 40th Annual Northeast Bioengineering Conference (NEBEC) IEEE , (2014). 978-1-4799-3728-8 Sarah A. Wilson, Michael V. Vilkhovoy, Steven P. Bevacqua and Susan C. Roberts Mechanical shearing Taxus plant suspension cultures reduces aggregation without affecting cell health , (2014). 1 2 6972977 , 10.1109/NEBEC.2014.6972977 http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=6972977
- M. K. Akitha Devi and P. Giridhar, Isoflavone Augmentation in Soybean Cell Cultures Is Optimized Using Response Surface Methodology, Journal of Agricultural and Food Chemistry, 62, 14, (3143), (2014).
- Kevin M Davies and Simon C Deroles, Prospects for the use of plant cell cultures in food biotechnology, Current Opinion in Biotechnology, 10.1016/j.copbio.2013.12.010, 26, (133-140), (2014).
- Sarah A. Wilson and Susan C. Roberts, Metabolic engineering approaches for production of biochemicals in food and medicinal plants, Current Opinion in Biotechnology, 26, (174), (2014).
- Jianfeng Xu and Ningning Zhang, On the way to commercializing plant cell culture platform for biopharmaceuticals: present status and prospect, Pharmaceutical Bioprocessing, 10.4155/pbp.14.32, 2, 6, (499-518), (2014).
- Milen I. Georgiev and Jost Weber, Bioreactors for plant cells: hardware configuration and internal environment optimization as tools for wider commercialization, Biotechnology Letters, 10.1007/s10529-014-1498-1, 36, 7, (1359-1367), (2014).
- Susan Howat, Bora Park, Il Suk Oh, Young-Woo Jin, Eun-Kyong Lee and Gary J. Loake, Paclitaxel: biosynthesis, production and future prospects, New Biotechnology, 31, 3, (242), (2014).
- Yi Li and Blaine A Pfeifer, Heterologous production of plant-derived isoprenoid products in microbes and the application of metabolic engineering and synthetic biology, Current Opinion in Plant Biology, 10.1016/j.pbi.2014.02.005, 19, (8-13), (2014).
- Rosa M. Cusido, Miriam Onrubia, Ana B. Sabater-Jara, Elisabet Moyano, Mercedes Bonfill, Alain Goossens, M. Angeles Pedreño and Javier Palazon, A rational approach to improving the biotechnological production of taxanes in plant cell cultures of Taxus spp., Biotechnology Advances, 32, 6, (1157), (2014).
- Yong-Cheng Li, Xuan-Xian Jiang and Xiao-Juan Long, Effects and action mechanisms of sodium fluoride (NaF) on the growth and cephalotaxine production of Cephalotaxus mannii suspension cells, Enzyme and Microbial Technology, 10.1016/j.enzmictec.2014.09.006, 67, (77-81), (2014).
- Sarah A Wilson, Elizabeth M Cummings and Susan C Roberts, Multi-scale engineering of plant cell cultures for promotion of specialized metabolism, Current Opinion in Biotechnology, 29, (163), (2014).
- Yong-Cheng Li, Enhanced cephalotaxine production in Cephalotaxus mannii suspension cultures by combining glycometabolic regulation and elicitation, Process Biochemistry, 10.1016/j.procbio.2014.10.005, 49, 12, (2279-2284), (2014).
- Tessa Moses, Jacob Pollier, Johan M. Thevelein and Alain Goossens, Bioengineering of plant (tri)terpenoids: from metabolic engineering of plants to synthetic biology in vivo and in vitro, New Phytologist, 200, 1, (27-43), (2013).
- Daan Van Elst, Sarah Nuyens, Braam van Wyk, Brecht Verstraete, Steven Dessein and Els Prinsen, Distribution of the cardiotoxin pavettamine in the coffee family (Rubiaceae) and its significance for gousiekte, a fatal poisoning of ruminants, Plant Physiology and Biochemistry, 67, (15), (2013).
- Philana V van Summeren-Wesenhagen and Jan Marienhagen, Putting bugs to the blush, Bioengineered, 10.4161/bioe.23885, 4, 6, (355-362), (2014).
- B. B. Misra and S. Dey, Culture of East Indian sandalwood tree somatic embryos in air-lift bioreactors for production of santalols, phenolics and arabinogalactan proteins, AoB Plants, 10.1093/aobpla/plt025, 5, 0, (plt025-plt025), (2013).
- Milen I. Georgiev, Regine Eibl and Jian-Jiang Zhong, Hosting the plant cells in vitro: recent trends in bioreactors, Applied Microbiology and Biotechnology, 10.1007/s00253-013-4817-x, 97, 9, (3787-3800), (2013).
- Supaart Sirikantaramas, Mami Yamazaki and Kazuki Saito, Camptothecin, New Light on Alkaloid Biosynthesis and Future Prospects, 10.1016/B978-0-12-408061-4.00005-5, (139-161), (2013).
- Moran Farhi, Magali Kozin, Shai Duchin and Alexander Vainstein, Metabolic engineering of plants for artemisinin synthesis, Biotechnology and Genetic Engineering Reviews, 29, 2, (135), (2013).
- Timothy J. McPartland, Rohan A. Patil, Michael F. Malone and Susan C. Roberts, Liquid–liquid extraction for recovery of paclitaxel from plant cell culture: Solvent evaluation and use of extractants for partitioning and selectivity, Biotechnology Progress, 28, 4, (990-997), (2012).
- Da‐Cheng Hao, Pei‐Gen Xiao, Guang‐Bo Ge and Ming Liu, Biological, Chemical, and Omics Research of Taxus Medicinal Resources, Drug Development Research, 73, 8, (477-486), (2012).
- Marizel G. Astello-García, María del Socorro Santos Díaz, Antonio Reyes-Agüero and Ana Paulina Barba de la Rosa, Opuntia spp. as a Source of Bioactive Compounds , Hispanic Foods: Chemistry and Bioactive Compounds, 10.1021/bk-2012-1109.ch008, (101-111), (2012).
- Preeti Shakya, Gregory Marslin, Karthik Siram, Ludger Beerhues and Gregory Franklin, Elicitation as a tool to improve the profiles of high‐value secondary metabolites and pharmacological properties of Hypericum perforatum, Journal of Pharmacy and Pharmacology, , (2017).
- Carlos Julio Nova-López, Jorge Mario Muñoz-Pérez, Luisa Fernanda Granger-Serrano, Mario Eveilio Arias-Zabala and Rafael Eduardo Arango-Isaza, Expresión de la proteína recombinante Cry 1Ac en cultivos de células de papa en suspensión: Establecimiento del cultivo y optimización de la producción de la biomasa y la proteína mediante la adición de nitrógeno, DYNA, 10.15446/dyna.v84n201.59829, 84, 201, (34), (2017).
- Yueya Zhang, Haifeng Yan, Meiyun Niu, Qingwei Cheng, Xinhua Zhang, Jaime A. Teixeira da Silva and Guohua Ma, Multiple strategies for increasing yields of essential oil and obtaining sandalwood terpenoids by biotechnological methods in sandalwood, Trees, 10.1007/s00468-017-1558-y, (2017).
- Sonam Chouhan, Kanika Sharma, Jian Zha, Sanjay Guleria and Mattheos A. G. Koffas, Recent Advances in the Recombinant Biosynthesis of Polyphenols, Frontiers in Microbiology, 10.3389/fmicb.2017.02259, 8, (2017).
- Vasil Georgiev, Anthony Ananga and Violeta Tsolova, Recent Advances and Uses of Grape Flavonoids as Nutraceuticals, Nutrients, 10.3390/nu6010391, 6, 1, (391-415), (2014).
- Sibongile Mafu and Philipp Zerbe, Plant diterpenoid metabolism for manufacturing the biopharmaceuticals of tomorrow: prospects and challenges, Phytochemistry Reviews, 10.1007/s11101-017-9513-5, (2017).
- Tasiu Isah, Shahid Umar, Abdul Mujib, Maheshwar Prasad Sharma, P. E. Rajasekharan, Nadia Zafar and Arajmand Frukh, Secondary metabolism of pharmaceuticals in the plant in vitro cultures: strategies, approaches, and limitations to achieving higher yield, Plant Cell, Tissue and Organ Culture (PCTOC), 10.1007/s11240-017-1332-2, (2017).
- Vasil Georgiev, Anton Slavov, Ivelina Vasileva and Atanas Pavlov, Plant cell culture as emerging technology for production of active cosmetic ingredients, Engineering in Life Sciences, , (2018).




