A Continuously Operated Bimembrane Reactor Process for the Biocatalytic Production of (2R,5R)-Hexanediol

Abstract

Alcohol dehydrogenase-catalyzed reductions of prochiral ketones to chiral alcohols require the regeneration of consumed cofactors such as NADH or NADPH. In the substrate-coupled cofactor regeneration approach, where 2-propanol is oxidized to acetone, complete conversion is inhibited by a thermodynamic limitation. This can be overcome by applying methods of in situ product removal techniques such as pervaporation. Here we present a new reactor concept which enables a continuous biocatalytic ketone reduction process with concurrent in situ removal of the byproduct acetone. In such a bimembrane reactor system recombinant Escherichia coli cells expressing alcohol dehydrogenase from Lactobacillus brevis were applied for the continuous reduction of 2,5-hexanedione. The product (2R,5R)-hexanediol could be synthesized with exceedingly high space-time yield of >170 g/(L·d) and catalyst usage (17.9 gP/gwetcellweight).