Recent advances in enzyme cascade reactions for the efficient synthesis of functionalized chemicals and complex pharmaceuticals

Enzyme cascades enable streamlined multi-step biocatalysis in one-pot systems, offering remarkable efficiency, selectivity, and sustainability compared to traditional chemical synthesis. This review highlights recent advances across three major directions: (i) efficient synthesis of bulk and chiral chemicals, including alcohol-to-amine conversion, polymer precursor biosynthesis, and non-canonical amino acid production; (ii) generation of complex pharmaceutical building blocks, exemplified by the synthesis of nucleotides, alkaloids, isoprenoids and their analogues; and (iii) integration of new-to-nature enzymatic reactions into metabolic pathways exemplified for engineered carbene-transferring P450s, artificial metalloenzymes, and photocatalytic active enzymes within microbial cell factories. These advances, driven by reaction route design, key enzyme engineering, and pathway/cell optimization, position enzyme cascades as transformative and versatile platforms for sustainable biomanufacturing across pharmaceuticals, chemicals, and materials.