首页|Continuous-flow enzymatic synthesis of chiral lactones in a three-dimensional microfluidic reactor
Continuous-flow enzymatic synthesis of chiral lactones in a three-dimensional microfluidic reactor
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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.
State Key Laboratory of Bioreactor Engineering,Shanghai Collaborative Innovation Center for Biomanufacturing,East China University of Science and Technology,Shanghai 200237,China
The Extreme Optoelectromechanics Laboratory,School of Physics and Materials Science,East China Normal University,Shanghai 200241,China
Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China