Recent advances and perspectives in multi-enzyme systems and immobilization for efficient rare sugars synthesis.

Rare sugars have attracted substantial interest owing to their critical roles in agriculture, cosmetics, food, and pharmaceutical industries. Traditional chemical synthesis methods face limitations such as low selectivity and environmental concerns. Consequently, enzymatic synthesis of rare sugars has emerged as an increasingly prominent research focus. To address the limitations of single-enzyme systems, multi-enzyme reactions have been developed as promising approaches, encompassing isomerases, epimerases, aldolases, phosphatases, oxidases, dehydratases, and associated coenzymes. Through the utilization of multi-enzyme systems, substrate costs can be reduced while the overall yields of rare sugars are enhanced. Furthermore, the application of immobilized enzymes is critical for optimizing the production process. Immobilization techniques can reduce reaction costs, improve enzyme properties, and enhance efficiency and stability. This review summarizes multi-enzyme systems for rare sugars biosynthesis and diverse immobilization methods, including traditional approaches, innovative nanomaterial-based techniques, and the use of scaffold proteins. Additionally, this review incorporates a techno-economic analysis of rare sugars production, addressing bottlenecks associated with enzyme stability and process costs, aiming to provide guidance for the industrial translation of rare sugar manufacturing technologies.