Post-genomic illumination of paclitaxel biosynthesis

Abstract

Paclitaxel rapidly became one of the most effective anticancer drugs. However, the production of paclitaxel is hindered by substantial challenges, particularly considering the significant quantities of drug required and the inherently low concentration of paclitaxel and its intermediates in plants. Paclitaxel is currently produced in a so-called semi-synthesis in which baccatin III is extracted from Taxus species and chemically converted to paclitaxel. Despite the fact that many of the intermediates of paclitaxel biosynthesis are yet to be experimentally determined, a set of recent papers—facilitated by the sequencing and assembly of three Taxus genomes—has uncovered the minimal gene sets for both baccatin III and paclitaxel biosynthesis. Here we summarize the key milestones towards our understanding of paclitaxel biosynthesis and highlight recent advancements made possible by genome-level analysis of potential key genes involved. We argue that these studies will ultimately pave the way towards the elucidation of the entire paclitaxel biosynthetic pathway and facilitate the industrial production of paclitaxel via synthetic biology approaches. However, several major challenges lie ahead before we can fully tap into the amazing curative potential that taxanes provide.