Taxanes: perspectives for biotechnological production

Abstract

Taxol is a valuable plant-derived drug showing activity against various cancer types. Worldwide efforts had been made to overcome the supply problem, because the supply by isolation from the bark of the slow-growing yew trees is limited. Plant cell cultures as well as chemical and biotechnological semisynthesis are processes, which are intensively investigated for the production of taxanes paclitaxel (Taxol) and docetaxel (Taxotere) in the last few years. This article provides a comparison of the current research on taxane biosynthesis and production in yew cell cultures.

Quantitative analysis of metabolic pathways in Catharanthus roseus hairy roots metabolically engineered for terpenoid indole alkaloid overproduction

“…Cell cultures are still used to produce the paclitaxel but a variety of fungal biosynthetic enzymes are being investigated to produce paclitaxel analogues [13]. Prospective production of taxanes is reviewed in Frense (2007) [14].…”

Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery

“…Stierle et al 1993;Strobel et al 1996Li et al 1998a, b;Noh et al 1999;Zhou and Ping 2001), no conclusive follow-up data concerning fungal metabolite profile or genetic background of the biosynthetic pathway leading to paclitaxel in fungi is available at present. While the pursuit of the idea of a microbial paclitaxel source, providing for an inexhaustible supply of this antineoplastic blockbuster and novel taxanes, is being hampered by obtaining disappointingly low yields, the active ingredient is still mainly derived via chemical semisynthesis from the advanced taxoid, 10-deacetylbaccatin III, readily available from the needles of the European yew tree, Taxus baccata, being a renewable source and, to a lesser extent, by means of plant cell culture methods (Leistner 2005;Frense 2007). Nonetheless, the exciting progress that has been made in the elucidation of biosynthetic route leading to paclitaxel in planta due to fundamental works of Croteau and his co-workers (Walker and Croteau 2001;Jennewein et al 2004a, b;Croteau 2005;DeJong et al 2006;Nims et al 2006), as well as the recent advances in microbial genomics (Zazopoulos et al 2003;Stephanopoulos et al 2004;Keller et al 2005;van Lanen and Shen 2006) and combinatorial biosynthesis (Floss 2006;Nguyen 2006;KleinMarcuschamer et al 2007), might still revive and boost the interest in endophytic paclitaxel synthesizers.…”

Efficient purification of paclitaxel from yews using high-performance displacement chromatography technique

“…A Shiseido Capcell Pak C 18 (AQ S-5 m) column (250 mm × 4.6 mm) was used in the HPDC technique on both small and large scale purifications. A Shiseido C 18 AQ column (50 mm × 20 mm, 20 m) was used as a trap column on large scale purification. Both Shiseido columns were purchased from JM Science, Grand Island, NY, USA.…”

“…As a result, over the past decades, renewable biomass of yew such as needles, twigs, and/or stems has been recognized as a valuable source of paclitaxel and its several semi-synthetic precursors having the same core skeleton. Numerous attempts to develop an economical and reliable alternative method for paclitaxel and docetaxel production have also been made, including chemical and semisynthesis [14,15], totalsynthesis [16,17], and the cell culture [18][19][20].…”