D-Serine as a Key Building Block: Enzymatic Process Development and Smart Applications within the Cascade Enzymatic Concept

Abstract

An efficient enzymatic method catalyzed by an enzyme from the d-threonine aldolase (DTA) family was developed for d-serine production at industrial scale. This process was used for the synthesis of two valuable ketoses, l-erythrulose and d-fructose, within the cascade enzymatic concept involving two other enzymes. Indeed, d-serine was used as a substrate of d-amino acid oxidase (DAAO) for the in situ generation of the corresponding α-keto acid, hydroxypyruvic acid (HPA), a key donor substrate of transketolase (TK). This enzyme catalyzed the irreversible transfer of the ketol group from HPA to an aldehyde acceptor to form a (3S)-ketose by stereoselective carbon–carbon bond formation. The compatibility of all enzymes and substrates allowed a sequential three-step enzymatic process to be performed without purification of the intermediates. This strategy was validated with two TK aldehyde substrates to finally obtain the corresponding (3S)-ketoses with high control of the stereoselectivity and excellent aldehyde conversion rates.