“…NADPH is involved in several processes for asymmetric synthesis of various pharmaceuticals and precursors, including ene- and ketoreductases (the latter also called alcohol dehydrogenases), transaminases, amine dehydrogenases, and imine reductases/reductive aminases among others. – This issue was addressed by using alternative regeneration systems such as a glucose dehydrogenase (GDH) with d -glucose, an alcohol dehydrogenase (ADH) with, e.g., isopropanol, and a phosphite dehydrogenase (PDH) with phosphite among others. , However, all of these systems demonstrate certain process limitations. For GDH, the synthesis of glucuronic acid requires additional pH regulation, while PDHs display a restricted range of optimal pH and temperature. , ADHs are temperature sensitive and might be problematic in reactions involving ketones, such as amine dehydrogenase or imine reductase-driven reductive aminations, , due to the reversibility of the alcohol oxidation, potentially leading to ketone reduction and alcohol side product formation. Hence, the pursuit of naturally existing FDHs that accept NADP + and the alteration of their coenzyme specificity through mutagenesis resulted in significantly enhanced variants that facilitate NADPH regeneration. ,– On the hydride donor site, less effort was made as only a couple of formate esters were identified to be suitable alternative substrates. , First investigations suggested that the reaction mechanism bears parallels to the A AC -1 type of ester hydrolysis (Scheme ).…”