Metabolic Engineering of Bacillus subtilis for High-Level Production of Salidroside from Potato Starch

Salidroside exhibits a diverse range of biological activities and is extensively utilized in the fields of biomedicine and cosmetics. Given the rising global demand, there is a critical need to develop more sustainable production methods for salidroside. This study implemented metabolic engineering strategies to enhance the biosynthesis of salidroside. The aromatic aldehyde synthase (AAS) from Petroselinum crispum was introduced to synthesize tyrosol from endogenous l-tyrosine. Competing metabolic pathways were suppressed, and endogenous alcohol dehydrogenase enzymes were screened. Additionally, a quorum-sensing-based dynamic regulation system was used to optimize salidroside production. The enzymes phosphoglucomutase (pgcA) and uridine diphosphate glucose pyrophosphorylase (gtaB) were overexpressed to balance the precursor supply. Finally, the engineered strain BS18 produced salidroside at 661.4 mg/L. This was achieved in shake-flask fermentation using potato starch as the carbon source. The study shows the potential for the large-scale production of salidroside in Bacillus subtilis. It provides a foundation for industrial applications and advances synthetic biology in natural product biosynthesis.