Multi-enzyme cascade reaction for stereoconvergent synthesis of (R)-decalactones

Chiral lactones are valuable aroma compounds which have wide applications in food and fragrance industries. However, the synthesis of chiral lactones often faces challenges such as low yield, poor stereoselectivity, high production costs and harsh reaction conditions. To overcome these issues, a novel multi-enzyme cascade reaction was designed to achieve dynamic resolution of decalactones through stereoconvergent preparation of hydroxydecanoic acids. Utilizing lactonase Rpa 3624 for hydrolysis, Hb KR for stereoselective oxidation, and Sm CR V4 for stereoselective reduction, 50 mM racemic γ -decalactone was stereoselectively converted into ( R )- γ -decalactone with 96.5 % ee and 89.2 % yield in 1 h. By replacing Sm CR V4 with Sm CR M5 , 50 mM racemic δ -decalactone was also efficiently converted into ( R )- δ -decalactone with excellent stereoselectivity of 95.5 % and 84.9 % yield. The one-pot process could be operated under mild conditions, enhanced atom economy and reduced production costs, and provides a sustainable approach for the synthesis of chiral decalactones. This work demonstrates the potential of multi-enzyme systems in synthesis of chiral lactones for industrial application.