ABSTRACT
Ene-reductases are used to reduce a large number of electron-deficient alkenes with exquisite stereoselectivities. However, the industrial utility of enzymes is also defined by additional factors such as substrate scope and enantioselectivity, productivity, enzyme stability under process conditions and ultimately enzyme and cofactor cost. Ene-reductases have a relatively small binding pocket limiting them to correspondingly small substrates. In early steps of chemical synthesis, this does not represent a problem; however, it hampers use of ene-reductases in the late-stage functionalization of more complex pharmaceutical molecules. Complementary approaches, which allow to circumvent the use of nicotinamide coenzymes, target the reduction of the ene-reductase bound FMN cofactor via photoreduction. Biocatalytic cascade reactions contain at least two consecutive enzymatic steps allowing to circumvent the isolation of reaction intermediates. Pregabalin, a gamma-aminobutyric acid derivative, functions as a calcium channel blocker and is used as an anticonvulsant drug, against neuropathic pain, as an adjunct therapy for partial seizures and in generalized anxiety disorders.
