Plant natural products are complex chemical compounds with important applications as pharmaceuticals, flavours, fragrances and colorants. Production of plant natural products in engineered microorganisms is an economic and sustainable alternative to inefficient chemical synthesis and limited natural resources. However, many valuable plant natural products, such as those used as pharmaceuticals, have very complex structures and their biosynthesis involves a large number of steps, hindering their biotechnological production. Our work aims to develop the tools and methods to efficiently produce complex plant natural products in the yeast Saccharomyces cerevisiae. Using the potent anticancer agent taxol as a prototype, we will develop continuous in vivo mutagenesis-based evolution, dedicated biosensors, optogenetically-controlled compartmentalization, and bioassay-coupled combinatorial biosynthesis to establish a blueprint for the successful biotechnological production of structurally complex plant natural products.