Highly Productive and Enantioselective Enzyme Catalysis under Continuous Supported Liquid-Liquid Conditions Using a Hybrid Monolithic Bioreactor.

Abstract

Enzyme-containing ionic liquids (ILs) were immobilized in cellulose-2.5-acetate microbeads particles embedded in a porous monolithic polyurethane matrix. This bioreactor was used under continuous liquid-liquid conditions by dissolving the substrates in a nonpolar organic phase immiscible with the ILs, thereby creating a biphasic system. Lipases (candida antarctica lipase B, CALB, candida rugosa lipase, CRL) were used to catalyze the enantioselective transesterification of racemic (R,S)-1-phenylethanol with vinyl butyrate and vinyl acetate, the esterification of (+/-)-2-isopropyl-5-methylcyclohexanol with propionic anhydride and the amidation of (R,S)-1-phenylethylamine with ethyl methoxyacetate. With this unique setup, very high productivities, that is, turnover numbers (TONs) up to 5.1×106 and space-time yields (STYs) up to 28 g product L-1 h-1 , exceeding the corresponding values for batch-type reactions by a factor of 3100 and 40, respectively, were achieved while maintaining or even enhancing enantioselectivity compared to batch reactions via kinetic resolution. To our best knowledge, this is the first continuously operated bioreactor using supported liquid-liquid conditions that shows these features in the synthesis of chiral esters and amides.