Paclitaxel, a natural product produced by yew trees, has become an important drug in the fight against cancer. Although more than 4 decades of research have identified numerous enzymes involved in paclitaxel synthesis, our understanding of this pathway’s architecture remains incomplete, and a few enzymes have yet to be identified. In a new article published in Nature , McClune and colleagues have developed a pipeline of multi-omics approaches to unravel the remaining enzymes performing key steps in the paclitaxel biosynthetic pathway. These findings open up new possibilities for producing this major anticancer drug using innovative biotechnological processes.