Transforming Peroxisomes into Organelle Factories for Monoterpene Production in Yeast Ogataea polymorpha

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Microbial production of natural products presents a promising alternative to traditional plant extraction. Recent metabolic engineering has employed subcellular compartmentalization to address the limitations of cytoplasmic engineering, while peroxisomes are emerging as an ideal orthogonal compartment for bioproduction. Ogataea polymorpha ( O. polymorpha ), as an industrial yeast used for protein expression, is also regarded as model organism for peroxisomal study due to its abundant peroxisomes. Here, we engineered peroxisomes into organelle factories for sustainable production of monoterpenes in O. polymorpha . With enhancing the supply precursor geranyl pyrophosphate (GPP), peroxisomes overproduced various GPP-derived monoterpenes, including geraniol (1030 mg∙L –1 ), β-myrcene (47 mg∙L –1 ), and (+)-borneol (120 mg∙L –1 ). Our work suggested O. polymorpha is a superior host for peroxisomal compartmentalization strategy to produce high-valued chemicals.