Statistically Optimized Continuous Stirred-Tank Reactor for Efficient and Scalable Enzymatic Synthesis of Puerarin Palmitate

Abstract Flavonoid esters are promising bioactive compounds for pharmaceutical and functional food applications because of their enhanced lipophilicity, stability, and biological activities. However, conventional batch processes are limited in their productivity and sustainability. In this study, a stable continuous enzymatic acylation system was developed for the efficient synthesis of flavonoid esters with a particular focus on puerarin palmitate. Key process variables and their interactions were systematically evaluated using statistical approaches, and under optimal conditions, the cumulative conversion and production reached 89.66% and 166.80 mg, respectively. The process was implemented in a continuous stirred-tank reactor (CSTR), maintaining an average conversion of 88.54% over 9 h of operation. The total production and productivity of puerarin palmitate were 1921.21 mg and 51.23 g/L/day, respectively, demonstrating the feasibility of continuous production. Ultimately, this study provides a scalable framework for sustainable flavonoid ester synthesis in pharmaceutical and food industries.