title: A rational approach to improving the biotechnological production of taxanes in plant cell cultures of Taxus spp.
abstract: Taxol is a complex diterpene alkaloid scarcely produced in nature and with a high anticancer activity. Biotechnological systems for taxol production based on cell cultures of Taxus spp. have been developed, but the growing commercial demand for taxol and its precursors requires the optimization of these procedures. In order to increase the biotechnological production of taxol and related taxanes in Taxus spp. cell cultures, it is necessary not only to take an empirical approach that strives to optimize in-put factors (cell line selection, culture conditions, elicitation, up-scaling, etc.) and out-put factors (growth, production, yields, etc.), but also to carry out molecular biological studies. The latter can provide valuable insight into how the enhancement of taxane biosynthesis and accumulation affects metabolic profiles and gene expression in Taxus spp. cell cultures. Several rational approaches have focused on studying the transcriptomic profiles of key genes in the taxol biosynthetic pathway in Taxus spp. cell cultures treated with elicitors such as methyl jasmonate, coronatine and cyclodextrins in relation with the taxane pattern, production and excretion to the culture medium. These studies have provided new insights into the taxol biosynthetic pathway and its regulation. Additionally, identifying genes with low levels of expression even in the presence of elicitors, together with metabolomics studies, has shed light on the limiting steps in taxol biosynthesis and could help define suitable metabolic targets for engineering with the main aim of obtaining highly productive Taxus cultured cells. In this review, we have summarized the latest endeavors to enhance the molecular understanding of the action mechanism of elicitors in Taxus spp. cell cultures. Developments in the ongoing search for new and more effective elicitation treatments and the application of metabolic engineering to design new transgenic cell lines of Taxus with an improved capacity for taxane production are described.
authors.affiliation: Secció de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn., 08028 Barcelona, Spain. Electronic address: rcusido@ub.edu.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Cusido
authors.affiliation: Departament de Ciències Experimentals i de Salut, Universitat Pompeu Fabra, C. Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Onrubia
authors.affiliation: Laboratorio de Fisiologia Vegetal, Facultad de Biologia, Universidad de Murcia, Campus de Espinardo, E-30100 Murcia, Spain. Electronic address: asj00482@um.es.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Sabater-Jara
authors.affiliation: Departament de Ciències Experimentals i de Salut, Universitat Pompeu Fabra, C. Doctor Aiguader 88, 08003 Barcelona, Spain. Electronic address: Elisabeth.moyano@upf.edu.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Moyano
authors.affiliation: Secció de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn., 08028 Barcelona, Spain. Electronic address: mbonfill@ub.edu.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Bonfill
authors.affiliation: Department of Plant Systems Biology, VIB, 9052 Ghent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium. Electronic address: algoo@psb.vib-ugent.be.
authors.forename: Alain
authors.initials: A
authors.lastname: Goossens
authors.affiliation: Laboratorio de Fisiologia Vegetal, Facultad de Biologia, Universidad de Murcia, Campus de Espinardo, E-30100 Murcia, Spain. Electronic address: mpedreno@um.es.
authors.forename: M
authors.initials: M
authors.lastname: Angeles Pedreño
authors.affiliation: Secció de Fisiologia Vegetal, Facultat de Farmacia, Universitat de Barcelona, Av. Joan XXIII sn., 08028 Barcelona, Spain. Electronic address: javierpalazon@ub.edu.
authors.forename: Javier
authors.initials: J
authors.lastname: Palazon
mesh_terms: D001709:Biotechnology / Q000379:methods*; D002478:Cells, Cultured; D060847:Metabolic Engineering / Q000379:methods*; D043823:Taxoids / Q000737:chemistry / Q000378:metabolism; D020946:Taxus / Q000166:cytology / Q000378:metabolism
chemical_list: D043823:Taxoids
keywords: Coronatine; Cyclodextrins; Elicitation; Metabolic engineering; Methyl jasmonate; Plant cell culture; Taxanes; Taxol; Taxus spp.; Transcriptomics