Recent Advances in Cofactor Regeneration Systems Applied to Biocatalyzed Oxidative Processes

Abstract

Abstract. Nowadays, the design of sustainable processes applicable at industrial scale is highly desirable due to environmental reasons. The use of biocatalytic reactions to carry out oxidative transformations is one of the possible strategies framed in here due to the mildness and usually high selectivities achieved with these methods. Anyway, while implementing this type of system at industrial scale several drawbacks must be overcome in order to obtain efficient setups. Historically, one of the main issues has been the cofactor-dependency of these biocatalysts to be active. Herein, we will show the state-of-the-art concerning the recent efforts developed in the design of (potentially) efficient methods to regenerate the cofactor in oxidative transformations. Thus, the more studied enzymatic methods will be discussed to highlight some recent examples dealing with the co-expression of both oxidative and recycling enzymes in one host or the development of self-sufficient biocatalysts. Furthermore, novel applications of these systems to couple two productive synthetic reactions will also be reviewed. Subsequently, we will focus on some recent examples related with the employment of electrochemical, photochemical, and chemical strategies to carry out the nicotinamide coenzyme or the flavin/heme prosthetic group regeneration. In the case of biocatalysts that use NAD(P) as electron shuttle, these systems have also been employed to replace it, allowing the design of nicotinamide-free recycling setups. In all cases, the (dis)advantages that these methodologies present will be briefly discussed.

Switching the Cofactor Specificity of an Imine Reductase

“…Furthermore, cofactor regeneration can drive the reaction to completion and allow the removal of oxidized cofactor. The development of various NAD(P)H cofactor regeneration processes has been subject to intensive studies . In most regeneration schemes for nicotinamide cofactors, the desired enzymatic reduction step is coupled to another enzymatic reaction.…”

Photobiocatalytic chemistry of oxidoreductases using water as the electron donor

“…The latter themselves are rather costly necessitating an enzymatic regeneration system to allow for their use in catalytic quantities. Today, a broad range of such regeneration systems are available, in principle solving this cofactor challenge [10][11][12][13] . The resulting multienzyme cascades ( Fig.…”

Large‐scale synthesis of tert‐butyl (3R,5S)‐6‐chloro‐3,5‐dihydroxyhexanoate by a stereoselective carbonyl reductase with high substrate concentration and product yield

“…During the past decade, a variety of SCRs have been identified and applied for the synthesis of (3 R ,5 S )‐CDHH or its derivatives with high yield and stereoselectivity . However, the requirement of expensive cofactor (NAD(P)H), narrow substrate spectrum and substrate insolubility limited the application of SCRs for the large‐scale production of (3 R ,5 S )‐CDHH . To date, there are no reports about the synthesis of (3 R ,5 S )‐CDHH in an industrial scale with high concentration of substrate.…”