Strategies for Cofactor Regeneration in Biocatalyzed Reductions

Selin Kara,Joerg H. Schrittu/ieser, and Frank Hollmann 

Synthetic Methods for Biolo caUy Active Molecule Exploring the Potential of Bioreductions, First Edition. Edited Elisabetta Brenna. 

The Most Relevant Cofactor Regeneration Approaches - and How to Choose the Most Suitable One 

Within living cells, NADH and NAD PH are present only in catalytic amounts. When consumed (oxidized) in the course of a biocatalytic reduction reaction, the corresponding oxidized cofactors (NAD(P) ) are re-reduced to enter a new catalytic reduction cycle. Hence NAD(P)H can also be seen as a redox mediator shuffling electrons from an oxidation reaction to the (desired) reduction reaction. In native cells, these NAD(P)H-producing oxidation reactions are mainly found in glycolysis and the citric acid cycle. 

Due to the high price of nicotinamide cofactors, their stoichiometric use in preparative biocatalytic reactions is prohibitive. Hence, for preparative application, in situ regeneration of the catalytically active, reduced form has been the preferred approach for many decades now [2a,3] and many excellent reviews are available summarizing the state of the art here la,4]. The most relevant approaches are summarized in Table 8.1 according to the nature of the 

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