Details

Autor(en) / Beteiligte

• Fu, Haigen
• Lam, Heather
• Emmanuel, Megan A
• Kim, Ji Hye
• Sandoval, Braddock A
• Hyster, Todd K

Titel

Ground-State Electron Transfer as an Initiation Mechanism for Biocatalytic C–C Bond Forming Reactions

Ist Teil von

• Journal of the American Chemical Society, 2021-06, Vol.143 (25), p.9622-9629

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The development of non-natural reaction mechanisms is an attractive strategy for expanding the synthetic capabilities of substrate promiscuous enzymes. Here, we report an “ene”-reductase catalyzed asymmetric hydroalkylation of olefins using α-bromoketones as radical precursors. Radical initiation occurs via ground-state electron transfer from the flavin cofactor located within the enzyme active site, an underrepresented mechanism in flavin biocatalysis. Four rounds of site saturation mutagenesis were used to access a variant of the “ene”-reductase nicotinamide-dependent cyclohexanone reductase (NCR) from Zymomonas mobiles capable of catalyzing a cyclization to furnish β-chiral cyclopentanones with high levels of enantioselectivity. Additionally, wild-type NCR can catalyze intermolecular couplings with precise stereochemical control over the radical termination step. This report highlights the utility for ground-state electron transfers to enable non-natural biocatalytic C–C bond forming reactions.