Enzymatic Asymmetric Reduction of Unfunctionalized C=C Bonds with Archaeal Geranylgeranyl Reductases

Abstract

The asymmetric reduction of activated C=C bonds such as enones is well established for non-enzymatic methods as well as in biocatalysis. However, the asymmetric reduction of unfunctionalized C=C bonds is mainly performed with transition metal catalysts whereas biocatalytic approaches are lacking. We have tested two FAD-dependent archaeal geranylgeranyl reductases (GGR) for the asymmetric reduction of isolated C=C bonds. The reduction of up to four double bonds in terpene chains with different chain lengths and head groups was confirmed. Methyl-branched E-alkenes were chemoselectively reduced in the presence of cyclic, terminal or activated alkenes. Using a removable succinate "spacer", farnesol and geraniol could be quantitatively reduced (>99 %). The reduction is strictly (R)-selective (enantiomeric excess >99 %). Hence, GGRs are promising biocatalysts for the asymmetric reduction of unactivated isolated C=C bonds, opening new opportunities for the synthesis of enantiopure branched alkyl chains.

Keywords: asymmetric catalysis; asymmetric hydrogenation; flavin adenine dinucleotide; lipids; oxidoreductases.