PUB - Publikationen an der Universität Bielefeld

Dehydrogenases which depend on nicotinamide coenzymes are of increasing interest for the preparation of chiral compounds, either by reduction of a prochiral precursor or by oxidative resolution of their racemate. The regeneration of oxidized and reduced nicotinamide cofactors is a very crucial step because the use of these cofactors in stoichiometric amounts is too expensive for application. There are several possibilities to regenerate nicotinamide cofactors: established methods such as formate/formate dehydrogenase (FDH) for the regeneration of NADH, recently developed electrochemical methods based on new mediator structures, or the application of gene cloning methods for the construction of ``designed'' cells by heterologous expression of appropriate genes. A very promising approach is enzymatic cofactor regeneration. Only a few enzymes are suitable for the regeneration of oxidized nicotinamide cofactors. Glutamate dehydrogenase can be used for the oxidation of NADH as well as NADPH while L-lactate dehydrogenase is able to oxidize NADH only. The reduction of NAD(+) is carried out by formate and FDH. Glucose-6-phosphate dehydrogenase and glucose dehydrogenase are able to reduce both NAD(+) and NADP(+). Alcohol dehydrogenases (ADHs) are either NAD(+)- or NADP(+)-specific. ADH from horse liver, for example, reduces NAD(+) while ADHs from Lactobacillus strains catalyze the reduction of NADP(+). These enzymes can be applied by their inclusion in whole cell biotransformations with an NAD(P)(+)-dependent primary reaction to achieve in situ the regeneration of the consumed cofactor. Another efficient method for the regeneration of nicotinamide cofactors is the electrochemical approach. Cofactors can be regenerated directly, for example at a carbon anode, or indirectly involving mediators such as redox catalysts based on transition-metal complexes. An increasing number of examples in technical scale applications are known where nicotinamide dependent enzymes were used together with cofactor regenerating enzymes.