Artificial biocatalytic cascades for the enantiocomplementary synthesis of 3-hydroxy-γ-butyrolactones

Abstract

Optically active 3-hydroxy-γ-butyrolactone (3HBL) serves as a key chiral synthon in organic synthesis and medicinal chemistry. Although several bio-based synthesis routes exist, the development of greener alternatives for producing enantiopure 3HBL remains highly desirable. Herein, we present a novel biocascade platform for the enantiocomplementary synthesis of chiral 3HBL using bio-based 1,3-dichloropropanol as a prochiral precursor. This biocascade strategy combines halohydrin dehalogenase-catalyzed dehalogenation–cyanation reactions with nitrilase-mediated hydrolysis–cyclization reactions, enabling the synthesis of both (S)- and (R)-3HBL with good yields and high optical purities. Furthermore, comparative analysis of single-cell (coexpressed enzymes) and two-cell (separately expressed enzymes) biocascade systems revealed that the single-cell approach offers superior catalytic efficiency, delivering higher product yield with reduced biocatalyst loading.