Tour de paclitaxel: biocatalysis for semisynthesis

Area of Science:

• Biotechnology
• Organic Chemistry
• Pharmacology

Background:

• Paclitaxel, a vital anti-cancer drug, was initially sourced from Pacific yew trees, posing ecological and economic challenges.
• The Food and Drug Administration (FDA) approved paclitaxel for ovarian and metastatic breast cancer treatment.
• Traditional extraction methods necessitate the destruction of yew trees, limiting sustainable supply.

Purpose of the Study:

• To review and present alternative, sustainable methods for paclitaxel production.
• To highlight the application of biocatalysis in the semisynthesis of paclitaxel.
• To introduce novel enzymes developed for efficient precursor generation.

Main Methods:

• Discovery and application of three novel enzymes: C-13 taxolase, C-10 deacetylase, and C-7 xylosidase.
• Utilizing a biocatalytic approach to convert various taxanes into 10-deacetylbaccatin III.
• Describing biocatalytic processes for preparing C-13 paclitaxel side chain synthons.

Main Results:

• The novel enzymes efficiently converted diverse taxanes into 10-deacetylbaccatin III, a crucial precursor for paclitaxel semisynthesis.
• Biocatalytic treatment increased 10-deacetylbaccatin III concentrations by 5.5- to 24-fold in various Taxus extracts.
• Established biocatalytic routes for synthesizing paclitaxel side chain components.

Conclusions:

• Biocatalysis offers a sustainable and efficient alternative for producing paclitaxel precursors.
• Semisynthesis, utilizing 10-deacetylbaccatin III and C-13 side chain synthons, provides a viable route to paclitaxel.
• This approach addresses the limitations of traditional paclitaxel sourcing from yew trees.