title: Development of a hazel cell culture-based paclitaxel and baccatin III production process on a benchtop scale.
abstract: The growing demand for the antitumorous agent paclitaxel and the difficulty in increasing its production by genetic engineering has prompted a search for new sources of taxanes. It has been reported that taxanes can be extracted from the angiosperm Corylus avellana L. Our aim was to improve taxane production by scaling up the process from mL-level to benchtop bioreactors, optimizing culture conditions and comparing the effect of two elicitors, 1 μM coronatine (Cor) and 100 μM methyl jasmonate (MeJA). Orbitally shaken flask cultures achieved a maximum fresh cell weight of 11.54 gDCW/L under control conditions, and MeJA- and Cor-treatment produced a statistically significant reduction in growth to 4.28 gDCW/L and 5.69 gDCW/L, while increasing the taxane content 3- and 27-fold, respectively. The enhancing effect of these elicitors on taxane production, despite affecting growth, was confirmed in orbitally shaken TubeSpin Bioreactors 50, where the highest taxane content (8583.3 μg/L) was obtained when 1μM Cor was used and elicitation took place at a packed cell volume of 50%. Two benchtop stirred bioreactors, BIOSTAT B plus and UniVessel SU, were compared, the latter providing a higher biomass of C. avellana cell suspension cultures. Transferring the established optimum culture conditions for taxane production to the UniVessel SU resulted in a total taxane content of 6246.1 μg/L, a 10-fold increase compared with shake flask experiments.
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Avda. Dr. Aiguader 80, E-08003 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Gallego
authors.affiliation: Zurich University of Applied Sciences, Institute of Biotechnology, Biochemical Engineering and Cell Cultivation Techniques, Campus Grüental, Wädenswill, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Imseng
authors.affiliation: Laboratori de Fisiología Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn, E-08028 Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Bonfill
authors.affiliation: Laboratori de Fisiología Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn, E-08028 Barcelona, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Cusido
authors.affiliation: Laboratori de Fisiología Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn, E-08028 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Palazon
authors.affiliation: Zurich University of Applied Sciences, Institute of Biotechnology, Biochemical Engineering and Cell Cultivation Techniques, Campus Grüental, Wädenswill, Switzerland.
authors.forename: Regine
authors.initials: R
authors.lastname: Eibl
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Avda. Dr. Aiguader 80, E-08003 Barcelona, Spain. Electronic address: elisabeth.moyano@upf.edu.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Moyano
mesh_terms: D000085:Acetates / Q000494:pharmacology; D000470:Alkaloids / Q000032:analysis / Q000378:metabolism*; D000596:Amino Acids / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000032:analysis / Q000378:metabolism; D018533:Biomass; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D031211:Corylus / Q000166:cytology*; D003517:Cyclopentanes / Q000494:pharmacology; D007192:Indenes / Q000494:pharmacology; D054883:Oxylipins / Q000494:pharmacology; D017239:Paclitaxel / Q000032:analysis / Q000378:metabolism*; D010937:Plant Growth Regulators / Q000494:pharmacology; D043823:Taxoids / Q000032:analysis / Q000378:metabolism*
chemical_list: D000085:Acetates; D000470:Alkaloids; D000596:Amino Acids; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D007192:Indenes; D054883:Oxylipins; D010937:Plant Growth Regulators; D043823:Taxoids; C073950:baccatin III; C058487:coronatine; C072239:methyl jasmonate; D017239:Paclitaxel
keywords: Benchtop bioreactor; Coronatine; Corylus avellana; Methyl jasmonate; Taxanes