Production of Taxanes in an Ionic Liquid-medium Two Phase Culture System

Abstract

We report here the effect of a hydrophobic ionic liquid (IL), 1-hexyl-3-methylimidazolium hexafluorophosphate ([C 6 MIM][PF 6 ]), for in situ extraction of hydrophobic taxanes such as 10-deacetyl baccatin III, baccatin III, cepharomannine and paclitaxel from an aqueous medium, on the production of the taxanes by Taxus cuspidata callus in the IL-medium two phase culture system. The effect of an additional elicitor, methyl jasmonate (MJ), on the production of the taxanes was also examined. The callus growth in the culture with the IL decreased compared to that without the IL. The production amount of 10-deacetyl baccatin III in the culture with the IL was enhanced significantly, which might cause the callus growth to decrease. Addition of MJ in the culture with the IL promoted the amount of cepharomannine produced. It was clear that [C 6 MIM][PF 6 ] was an effective solvent for extraction and production of the taxanes in the callus culture.

Effect of Methyl Jasmonate on Production of Paclitaxel and Related Taxanes in a Hydrophobic Ionic Liquid-Medium Two Phase Culture System

“…Magnetic ILs such as benzyltrioctylammonium bromotrichloroferrate (III) and 1,12-di(3-hexadecylbenzimidazolium) dodecane bis[(trifluoromethyl)-sulfonyl]imide bromotrichloroferrate (III) have higher extraction efficiencies for DNA molecules [14]. We reported the enhancement of PTX and with the in situ extraction of these compounds by HMIM-PF 6 [6]. Figure 1 shows the metabolic pathway of PTX and the related taxanes from geranylgeranyl diphosphate [11].…”

“…Two phase culture systems using water-immiscible liquids such as organic solvents and ionic liquids (ILs) have been proposed for the in situ extraction of hydrophobic PTX from the culture medium via their hydrophobic interaction to decrease the PTX's inhibition, [3][4]. We reported on the use of more hydrophobic organic solvents such as lauryl alcohol and ILs such as 1-hexyl-3-methylimidazolium hexafluorophosphate (HMIM-PF 6 ) for the in situ extraction of paclitaxel from the aqueous medium [5][6]. As harmless solvents in contrast to conventional organic solvents, ILs have attracted attention because of their special features such as high thermal stability, negligible volatility, and selective solubility.…”

“…Elicitors such as methyl jasmonate (MJ) and jasmonic acid have been used to increase the productivities of the secondary metabolites such as the taxanes [6,16]. In the present research the effect of MJ addition on the enhancement of the production amount of the taxanes by the in situ extraction in plant cell culture including P14-TFSI was investigated.…”

Enhancement of Paclitaxel Production in Plant Cell Culture Including Increased Amount of Water-immiscible 1-Butyl-1-methylpyrrolidinium Bis(trifluoromethanesulfonyl)imide

“…Two-phase culture system using hydrophobic solid absorbents and water-immiscible liquids has been proposed for the in situ extraction and absorption of hydrophobic paclitaxel from the culture medium, respectively [4][5][6]. We reported the effectiveness of hydrophobic organic solvents such as lauryl alcohol for the production of paclitaxel in the plant cell culture [7,8]. Recently, ionic liquids (ILs) have been paid attention to as substitutes of conventional organic solvents for the extraction of bioactive compounds from biomass.…”

“…We found that the enhancement of paclitaxel in the plant cell culture with the in situ extraction of the compounds of the taxanes by hydrophobic ILs and 1-butyl-1-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (P14-TFSI), which has more hydrophobic than 1-hexyl-3-methylimidazolium hexafluorophosphate (HMIM-PF 6 ) [19], enhanced the productivity of paclitaxel, BIII, 10-DAB, and cepharomannine (CM). Moreover, methyl jasmonate (MJ), a well-known elicitor which can stimulate stress responses in plants leading to enhancement of synthesis of secondary metabolites such as paclitaxel, has been used to increase the productivity of paclitaxel [8,20].…”