Work

Enzymatic Synthesis of Enantiopure ( R )‐Citronellal from Geraniol via a Short‐Chain Dehydrogenase and Ene Reductase

Year: 2025

Type: article

Abstract: The development of synthetic routes to produce enantiopure ( R )‐citronellal as a key intermediate for the synthesis of (–)‐menthol and other valuable terpenoids is highly relevant in the pharmaceutical, flavor, and fragrance industries. Herein, we showcase a cascade with two consecutive biocatalytic steps performed separately using the inherent selectivity of a short‐chain alcohol dehydrogenase (SDR) and an ene reductase (ERED) from the Old Yellow Enzyme (OYE) family. The first reaction involves the Aa SDR1‐catalyzed oxidation of relatively inexpensive geraniol in a biphasic system, providing geranial as an intermediate. The organic phase containing geranial is then extracted and transferred to the second step, where the ERED variant OYE2_Y83V catalyzes the asymmetric reduction of geranial to produce ( R )‐citronellal, achieving >90% conversion and >99% enantiomeric excess. The use of n ‐heptane in a two‐liquid phase system not only facilitates substrate and product solubilization but also minimizes geranial isomerization. This biocatalytic cascade therefore enables the synthesis of enantiopure ( R )‐citronellal.

Source: Advanced Synthesis & Catalysis

DOI: 10.1002/adsc.202500060

Authors: Claudia Ferrer‐Carbonell, Rocio Villa, Iris Viskaal, Diederik J. Opperman, Caroline E. Paul

Institutions: Delft University of Technology, Universidad de Murcia, University of the Free State

Language: English

Topic: Enzyme Catalysis and Immobilization

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,650

Funders: European Commission, Technische Universiteit Delft, Universidad de Murcia, European Research Council