Wang H,
Gao B,
Chen H,
Cao S,
Ma X,
Chen Y,
Ye Y *.
Westlake University, Hangzhou, P. R. China
Unmasking the Reverse Catalytic Activity of ‘Ene’-Reductases for Asymmetric Carbonyl
Desaturation.
Nat. Chem. 2025;
17: 74-82
DOI:
10.1038/s41557-024-01671-1
Keywords
desymmetrizing - cyclohexenones - ‘ene’-reductases - directed evolution - reverse
catalysis - desaturation - biocatalysis
Significance
The Ye group developed a biocatalytic platform using reengineered ‘ene’-reductases
for
asymmetric carbonyl desaturation. It facilitates the enantioselective
dehydrogenation of cyclohexanones, producing versatile chiral cyclohexenones under
mild conditions. By employing directed evolution, the platform achieves enhanced
enantioselectivity while tolerating diverse substituents and minimizing the need for
harsh reagents. This sustainable approach not only addresses limitations of
traditional methods but advances the fields of asymmetric synthesis and
biocatalysis, offering a promising alternative for complex molecular
transformations.
Comment
Recent advancements have shown that flavin-dependent ‘ene’-reductases (EREDs) are
powerful tools for enabling a variety of reductive radical transformations,
highlighting the potential of directed evolution in the development of novel
enzymatic catalysis. In this study, the authors expand the ERED mutation pool and
reveal their applications in oxidative dehydrogenation. Notably, the reverse
catalytic processis a reduction, opening up new possibilities for the development
of
innovative biocatalytic oxidation reactions.
