Improved paclitaxel and baccatin III production in suspension cultures of Taxus media.
A cell suspension culture of Taxus media was established from a stable callus line of this species. The growth rate and production of paclitaxel and baccatin III of this cell suspension were significantly increased during the shake flask culture in its respective optimum media for cell growth and product formation, which were selected after assaying 24 different culture media. The highest yields of paclitaxel (2.09 mg L(-1)) and baccatin III (2.56 mg L(-1)) in the production medium rose (factors of 7.0 and 3.0, respectively) in the presence of methyljasmonate (220 microg g(-1) FW). When the elicitor was added together with mevalonate (0.38 mM) and N-benzoylglycine (0.2 mM), the increase in the yields of paclitaxel and baccatin III was even higher (factors of 8.3 and 4.0, respectively). Thereafter, a two-stage culture for cell suspension was carried out using a 5-l stirred bioreactor running for 36 days, the first stage being in the cell growth medium until cells entered their stationary growth phase (12 days) and the second stage being in the production medium supplemented with the elicitor and two putative precursors in the concentrations indicated above. Under these conditions, 21.12 mg L(-1) of paclitaxel and 56.03 mg L(-1) of baccatin III were obtained after 8 days of culture in the production medium.
Cusidó
Rosa M
RM
Laboratorio de Fisiologia Vegetal, Facultad de Farmacia, Universidad de Barcelona, Avda. Diagonal 643, 08028 Barcelona, Spain.
Palazón
Javier
J
Bonfill
Mercedes
M
Navia-Osorio
Alberto
A
Morales
Carmen
C
Piñol
M Teresa
MT
D000470:Alkaloids / Q000096:biosynthesis*; D000972:Antineoplastic Agents, Phytogenic / Q000096:biosynthesis*; D019149:Bioreactors; D003470:Culture Media; D017239:Paclitaxel / Q000096:biosynthesis*; D043823:Taxoids; D020946:Taxus / Q000166:cytology / Q000378:metabolism*
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D003470:Culture Media; D043823:Taxoids; C073950:baccatin III; D017239:Paclitaxel