Current approaches for the production of high-value compounds in microorganisms mostly use the cytosol as a general reaction vessel. However, competing pathways and metabolic cross-talk frequently prevent efficient synthesis of target compounds in the cytosol. Eukaryotic cells control the complexity of their metabolism by harnessing organelles to insulate biochemical pathways. Inspired by this concept, herein we transform yeast peroxisomes into microfactories for geranyl diphosphate-derived compounds, focusing on monoterpenoids, monoterpene indole alkaloids, and cannabinoids. We introduce a complete mevalonate pathway in the peroxisome to convert acetyl-CoA to several commercially important monoterpenes and achieve up to 125-fold increase over cytosolic production. Furthermore, peroxisomal production improves subsequent decoration by cytochrome P450s, supporting efficient conversion of (S)-(-)-limonene to the menthol precursor trans-isopiperitenol. We also establish synthesis of 8-hydroxygeraniol, the precursor of monoterpene indole alkaloids, and cannabigerolic acid, the cannabinoid precursor. Our findings establish peroxisomal engineering as an efficient strategy for the production of isoprenoids.

目前在微生物中生产高价值化合物的方法大多使用胞质溶胶作为一般反应容器。但是，竞争途径和代谢串扰经常阻止目标化合物在细胞质中的有效合成。真核细胞通过利用细胞器隔离生化途径来控制其代谢的复杂性。受此概念的启发，本文将酵母过氧化物酶体转化为用于衍生自香叶基二磷酸酯的化合物的微型工厂，重点关注单萜类，单萜吲哚生物碱和大麻素。我们在过氧化物酶体中引入了一个完整的甲羟戊酸途径，将乙酰辅酶A转化为几个具有商业意义的单萜，并实现了比胞质生产最多125倍的增长。此外，S）-（-）-柠檬烯制得薄荷醇前体反式-异胡椒醇。我们还建立了8-羟基香叶醇（单萜吲哚生物碱的前体）和大麻二酚酸（大麻素的前体）的合成。我们的发现将过氧化物酶体工程学确定为生产类异戊二烯的有效策略。