De novo biosynthesis of cannabinoids and their analogs in Yarrowia lipolytica

Abstract Cannabis sativa has long been a cornerstone of both medicinal and cultural practices, with its therapeutic use spanning over 2700 years. Central to its therapeutic effects are cannabinoids, which interact with the endocannabinoid system to influence various physiological processes such as anxiety, pain, and inflammation. Despite its benefits, cannabinoid production faces challenges and scarcity from plant extraction. This work leverages Yarrowia lipolytica as a platform for cannabinoid biosynthesis. By optimizing the precursor supply, engineering biomolecular condensate-like dual prenyltransferase expression