De novo biosynthesis of lavandulol and lavandulyl acetate in Escherichia coli

Lavandulol and its acetate ester, lavandulyl acetate, are valuable irregular monoterpenes found in lavender essential oil, widely utilized in the food and cosmetic industries. Due to the limitations of extraction from natural plant resources, developing sustainable microbial cell factories for their production is of great interest. Here, we report the first de novo biosynthesis of lavandulol and lavandulyl acetate in Escherichia coli . Initially, a heterologous mevalonate (MVA) pathway was coupled with lavandulyl diphosphate synthase (LPPS) to establish the biosynthetic route from glycerol. To relieve pathway bottlenecks, we overexpressed the endogenous dITP/XTP pyrophosphatase RdgB, which efficiently facilitated the dephosphorylation of the precursor lavandulyl diphosphate (LPP), increasing lavandulol titers to 42.87 mg/L. Subsequently, the alcohol acyltransferase ATF1 from Saccharomyces cerevisiae was identified as the most effective enzyme for acetylating lavandulol. By integrating ATF1 into the pathway and optimizing both the host strain and fermentation process, we achieved a final lavandulyl acetate titer of 89.43 mg/L. This study establishes a promising prokaryotic platform for the efficient biosynthesis of high-value irregular monoterpenes.