A microfactory in yeast peroxisomes

Synthetic Biology Considerable synthetic biology efforts are focused on engineering yeast to produce valuable metabolites. Production in the cytosol can be challenging because of toxicity or crosstalk with cellular pathways. Dusseaux et al. harnessed the yeast peroxisome to produce geranyl diphosphate (GPP), a precursor to monoterpenoids, monoterpene indole alkoids, and cannabinoids. Targeting the entire pathway for GPP synthesis, along with an enzyme that converts GPP to the monoterpene limonene, to the peroxisome gives a 125-fold improvement in yield of limonene compared with production in the cytoplasm. Additional monoterpenes can be synthesized with the same platform using the appropriate monoterpene synthase. Peroxisomal production also facilitates downstream processing involving oxidation by cytochrome P450 enzymes. Peroxisome microfactories could be used for the modular assembly and optimization of other complex pathways. Proc. Natl. Acad. Sci. U.S.A. 117 , 31789 (2020).