Multienzym

Multienzym is a term in biocatalysis for systems in which two or more enzymes act together to convert a substrate through a sequence of reactions. These systems may be natural enzyme complexes or engineered assemblies designed to promote substrate channeling, where intermediates pass directly between active sites, often within a single reactor or cell.

Architectures include fusion proteins that tether enzymes in a defined order, scaffolded constructs that arrange enzymes on protein or nucleic acid scaffolds, co-immobilization on solid supports, and compartmentalization in vesicles or microdroplets.

Substrate channeling can increase local concentration of intermediates, improve overall reaction rates, and reduce side reactions, enabling one-pot syntheses that would require multiple steps.

Challenges include finding conditions compatible for all enzymes, balancing stoichiometry and expression, ensuring stability, avoiding unwanted interactions, and managing costs.

Applications span industrial biocatalysis, pharmaceutical synthesis, biomass conversion, and biosensing. In nature, multienzyme complexes such as the pyruvate dehydrogenase and fatty acid synthase systems illustrate efficiency gained from organization. Engineered multienzyme assemblies have been used for cascades like glucose oxidase coupled to peroxidase for detection and for improved cellulase activity in cellulose degradation.

The term is sometimes used interchangeably with enzyme cascade systems or multi-enzyme complexes, reflecting a broad and evolving area in synthetic biology and metabolic engineering.