Advances in Gastrodin Production: From Native to Engineered Biosynthesis

ABSTRACT: Gastrodin is a phenolic glycoside and the principal bioactive compound of Gastrodia elata. Owing to its potent neuroprotective, antioxidant, and therapeutic properties, gastrodin has attracted increasing attention and is now widely applied in the pharmaceutical, healthcare, and food industries. Traditional extraction of gastrodin is constrained by limited raw material availability and low yield, making it insufficient to meet the growing market demand. In recent years, microbial biosynthesis has become a preferred route for gastrodin production due to its sustainability, economic feasibility, and high safety. Therefore, developing metabolically engineered strains with enhanced genetic stability, high productivity, and efficient substrate utilization has become an urgent priority for achieving gastrodin biosynthesis. This review introduces the discovery and biosynthetic routes of gastrodin, summarizes its production methods, and discusses recent advances across various microbial chassis systems. It further highlights recent advances in pathway reconstruction and metabolic optimization, with an emphasis on strategies to enhance precursor flux, optimize UDP-glucose biosynthesis and regeneration, and improve glycosyltransferase catalytic activity through protein engineering. Overall, this review provides insights and future directions for developing efficient, genetically stable, and industrially scalable microbial cell factories for sustainable gastrodin production.