Recent advances in artificial enzyme cascades for the production of value-added chemicals

Enzyme cascades are efficient tools to perform multi-step synthesis in one-pot in a green and sustainable manner, enabling non-natural synthesis of valuable chemicals from easily available substrates by artificially combining two or more enzymes. Bioproduction of many high-value chemicals such as chiral and highly functionalised molecules have been achieved by developing new enzyme cascades. This review summarizes recent advances on engineering and application of enzyme cascades to produce high-value chemicals (alcohols, aldehydes, ketones, amines, carboxylic acids, etc) from simple starting materials. While 2-step enzyme cascades are developed for versatile enantioselective synthesis, multi-step enzyme cascades are engineered to functionalise basic chemicals, such as styrenes, cyclic alkanes, and aromatic compounds. New cascade reactions have also been developed for producing valuable chemicals from bio-based substrates, such as ʟ-phenylalanine, and renewable feedstocks such as glucose and glycerol. The challenges in current process and future outlooks in the development of enzyme cascades are also addressed.