Biocatalytic Cascade from Geraniol to Enantiopure ( R )-Citronellal Using an Aryl-Alcohol Oxidase and Ene Reductase

Abstract (R)-Citronellal, a key intermediate for (−)-menthol and other valuable fragrance compounds, is traditionally synthesized by unsustainable chemical methods, with low selectivity. Herein, we report a one-pot enzymatic cascade converting geraniol to enantiopure (R)-citronellal using Streptomyces hiroshimensis aryl-alcohol oxidase ShAAO and ene reductase Saccharomyces cerevisiae OYE2_Y83V. A scale-up reaction at 100 mM geraniol produced 95 mg of (R)-citronellal with an enantiomeric excess of >99.8%, demonstrating a sustainable, preparative-scale, and highly selective route to chiral terpenoids.