Abstract
A new continuous-flow process for the enzymatic synthesis of optically pure γ-lactones,which are used as flavors and fragrances in the food and cosmetic industries,was developed in a three-dimensional microfluidic reactor.The microchannels(175 mm in length,0.9 mm in depth,and 1.72 mL in volume)were carved precisely inside a single borosilicate glass(90 mm × 75 mm × 12 mm)with ultrafast fem-tosecond laser micromachining.The flow field analysis and reaction simulation showed that the mix-ing of substrates and enzymes was enhanced,allowing the adjustment of residence time in a wide win-dow.SmCRV4,a carbonyl reductase with excellent catalytic activity and enantioselectivity toward γ/δ-keto acids,was employed for the asymmetric synthesis of various chiral lactones.30mmol/L(R)-y-decalactone(3g)can be obtained in 26 s with a space-time yield(STY)up to 16,877 g L-1 d-1,which is 14.4 times higher than the highest STY of batch reaction reported previously.This continuous-flow process was ap-plied to the synthesis of 6 chiral lactones.In addition,the scaled-up synthesis of 3g was carried out in 6 cascade microreactors continuously for 6h,demonstrating the feasibility and stability of the 3D continuous-flow process in enzymatic synthesis of optically pure compounds.