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

Structurally diverse gamma- and delta-lactones were efficiently synthesized stereoselectively using an engineered carbonyl reductase from Serratia marcescens (SmCRV4). SmCRV4 exhibited improved activity (up to 500-fold) and thermostability toward 14 gamma-/delta-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 gamma- and delta-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)-gamma-decalactone.