Nicotinamide-dependent Ene reductases as alternative biocatalysts for the reduction of activated alkenes

Article abstract of DOI:10.1002/ejoc.201200776

Four NAD(P)H-dependent non-flavin ene reductases have been investigated for their ability to reduce activated C=C bonds in an asymmetric fashion by using 20 structurally diverse substrates. In comparison with flavin-dependent Old Yellow Enzyme homologues, a higher degree of electronic activation was required, because the best activities were obtained with enals and nitroalkenes rather than enones and carboxylic esters. Although FaEO from Fragaria x ananassa (strawberry) and its homologue SlEO from Solanum lycopersicum (tomato) exhibited a narrow substrate spectrum, progesterone 5β-reductase (At5β-StR) from Arabidopsis thaliana (thale cress) and leukotriene B₄ 12-hydroxydehydrogenase (LTB₄DH/PGR) from Rattus norvegicus (rat) appear to be promising candidates, in particular for the asymmetric bioreduction of open-chain enals, nitroalkenes and α,β-unsaturated γ-butyrolactones. Competing nitro reduction and non-enzymatic Weitz-Scheffer epoxidation were largely suppressed. Electronically activated alkenes have been stereoselectively reduced by using a single-enzyme-cofactor system employing nicotinamide-dependent non-flavin ene reductases. Copyright