Elucidation and recreation of the biosynthetic pathway for taxol

Paclitaxel (sold as Taxol) is taxane diterpene natural product of yew trees (Taxus spp.)  and a potent stabilizer of microtubules that is effective in treatment of cancers. However, it has proven difficult to elucidate its biosynthetic pathway, and commercial production still relies on extracting an intermediate, baccatin III, from yew tissues. In an elegant new work by McClune and Liu et al., the authors used a novel approach to identify genes involved in paclitaxel synthesis. By doing so, they discovered several new genes in the pathway, enabling them to synthesize baccatin III heterologously in Nicotiana benthamiana leaves. Part of the challenge lies in the fact that yews produce hundreds of closely related taxanes, and correspondingly hundreds of candidate biosynthetic genes. The authors developed a new pipeline to search for these elusive paclitaxel genes which they termed multiplexed perturbation × single nuclei (mpXsn). One of the key advantages of this process is that they were able to simultaneously profile cells from many tissues, developmental stages, and responding to various potential inducers of paclitaxel synthesis. Interestingly, several of the genes that they identified had not previously been considered as candidates. Not only does this work provide an exciting new process for Taxol synthesis that does not require harvesting yew tissue, but the mpXsn technology does not require any genetic tools so is generalizable to diverse, non-model species. (Summary by Mary Williams @PlantTeaching.bsky.social) Nature 10.1038/s41586-025-09090-z