Rationally

engineering a favorable physicochemical microenvironment for enzymes has recently emerged as an effective strategy to improve their catalytic performance. In this review

we discuss four microenvironmental effects according to the mechanism of action: localizing and excluding reactants and regulators

regulating microenvironmental pH

creating a water-like microenvironment

and increasing the local temperature. These mechanisms are enzyme-independent and can in principle be used in combination to tailor enzyme behaviors

offering new approaches to enabling

enhancing

and regulating enzyme catalysis in diverse applications without the need for genetic engineering.