Tunable Production of ( R )- or ( S )-Citronellal from Geraniol via a Bienzymatic Cascade Using a Copper Radical Alcohol Oxidase and Old Yellow Enzyme.

Biocatalytic pathways for the synthesis of (-)-menthol, the most sold flavor worldwide, are highly sought-after. To access the key intermediate ( R )-citronellal used in current major industrial production routes, we established a one-pot bienzymatic cascade from inexpensive geraniol, overcoming the problematic biocatalytic reduction of the mixture of ( E/Z )-isomers in citral by harnessing a copper radical oxidase ( Cgr AlcOx) and an old yellow enzyme (OYE). The cascade using OYE2 delivered 95.1% conversion to ( R )-citronellal with 95.9% ee , a 62 mg scale-up affording high yield and similar optical purity. An alternative OYE, GluER, gave ( S )-citronellal from geraniol with 95.3% conversion and 99.2% ee .