Efficient Stereoselective Synthesis of Structurally Diverse γ- and δ-Lactones Using an Engineered Carbonyl Reductase

Graphical Great engineering ! In this work, structurally diverse γ- and δ-lactones were efficiently stereoselectively synthesized using an engineered carbonyl reductase from Serratia marcescens ( Sm CR V4 ). Sm CR V4 exhibited improved activity and thermostability toward 14 γ-/δ-keto acids and esters compared with the wild-type enzyme, with 110-fold enhancement in catalytic efficiency ( k cat / K m ) toward methyl 4-oxodecanoate. The preparative synthesis of alkyl and aromatic γ- and δ-lactones with 95 %–>99 % ee was demonstrated. The highest space-time yield, 1175 g L −1 d −1 , was achieved for ( R )-γ-decalactone. Structurally diverse γ- and δ-lactones were efficiently synthesized stereoselectively using an engineered carbonyl reductase from Serratia marcescens ( Sm CR V4 ). Sm CR V4 exhibited improved activity (up to 500-fold) and thermostability toward 14 γ-/δ-keto acids and esters, compared with the wild-type enzyme, with 110-fold enhancement in catalytic efficiency ( k cat / K m ) toward methyl 4-oxodecanoate. The preparative synthesis of alkyl and aromatic γ- and δ-lactones with 95 %–>99 % ee and 78 %–90 % yields was demonstrated. The highest space-time yield, 1175 g L −1 d −1 , was achieved for ( R )-γ-decalactone.