Transforming yeast peroxisomes into microfactories for the efficient production of high-value isoprenoids

Significance Monoterpenoids, monoterpene indole alkaloids, and cannabinoids are highly valued for their fragrant and therapeutic properties, but sourcing them from nature or deriving them from petrochemicals is no longer sustainable. However, sustainable production of these compounds in engineered microorganisms is mostly hampered by the limited availability of the main building block in their biosynthesis, geranyl diphosphate. Here, we overcome this challenge by engineering yeast peroxisomes as geranyl diphosphate-synthesizing microfactories and unlock the potential of yeast to produce a wide range of high-value isoprenoids. Conceptually, in this work we develop peroxisomes as synthetic biology devices that can be used for the modular assembly and optimization of complex pathways, adding an extra level of hierarchical abstraction in the systematic engineering of cell factories.