Biosynthesis of lavandulol and lavandulyl acetate in Escherichia coli

Lavandulol and its ester derivative, lavandulyl acetate, are key fragrance constituents of lavender essential oil with widespread applications in cosmetics, perfumery, and food. However, traditional plant extraction suffers from low yield and unsustainable practices, and chemical synthesis relies on petrochemical feedstocks. Here, we report the first de novo microbial biosynthesis of lavandulol and lavandulyl acetate in Escherichia coli through modular pathway engineering. By screening 13 pyrophosphatases from E. coli, we identified RdgB as an efficient pyrophosphatase catalyzing the conversion of lavandulyl diphosphate into lavandulol, enabling its production at 24.9 mg/L. Building on this, we established a three-plasmid expression system and introduced a lavender-derived alcohol acyltransferase, LiAAT4, to achieve the biosynthesis of lavandulyl acetate at 42.4 mg/L. This study establishes the biosynthetic route to lavandulol in E. coli, demonstrating a viable and sustainable microbial platform for producing significant natural components of lavender oil. Our work provides the basis for future strain optimization and industrial-scale biomanufacturing of high-value monoterpene fragrance molecules.