Bioorg Chem. 2026 Mar 9;174:109732. doi: 10.1016/j.bioorg.2026.109732. Online ahead of print.
ABSTRACT
Nitrile-containing compounds are significant in pharmaceutical, agrochemical, and materials science. Despite considerable progress in cyanidation methods, these protocols mainly rely on toxic cyanating reagents and chiral metal complexes. Photoenzymatic catalysis combines the high reactivity of photochemistry with the precise stereochemical control of biocatalysis. Here, we report a photoenzymatic hydrocyanoalkylation of olefins, which employs the engineered flavin-dependent “ene”-reductases (EREDs) as biocatalysts to produce a variety of γ-stereogenic nitriles with high yield and enantioselectivity. Mechanistic experiments, including computational simulations, reveal that the hydrocyanoalkylation reaction is initiated via excitation of electron donor-acceptor (EDA) complexes and stereoselectively quenches through hydrogen atom transfer (HAT) by flavin semiquinone (FMNsq). This strategy expands the potential of enzymes for the non-natural biocatalytic transformations in the synthesis of chiral alkyl nitriles.
PMID:41819744 | DOI:10.1016/j.bioorg.2026.109732