Integrating Hydrolase Biocatalysis with Chemo-, Electro-, and Photocatalysis: Emerging Strategies for Sustainable Organic Synthesis

Abstract

A major goal in modern synthetic chemistry is to develop sustainable and cost-efficient methodologies for the synthesis of complex, chiral molecules-particularly those with pharmaceutical importance. In this context, there are different types of approaches being used for the sustainable synthesis of organic molecules, including biocatalysis, electrosynthesis, and photocatalysis. Enzymes, or biocatalysts, are integral to synthetic chemistry, offering exceptional chemo-, regio-, and enantioselectivity while operating under mild and environmentally benign conditions. Despite these advantages, their application is often limited by narrow substrate scope and restricted reactivity. To overcome these limitations, one promising approach is to integrate biocatalysis with other catalytic techniques. These integrated strategies offer new opportunities for selective and green synthesis. However, a significant challenge lies in the potential deactivation of enzymes when used alongside other catalysts, which can compromise the overall catalytic efficiency. To address this challenge, it is essential to identify reaction conditions that preserve the stability and activity of each catalytic component. Achieving such compatibility is key to enabling efficient multi-catalytic cascade processes for the synthesis of drug-like compounds. This review highlights recent progress, particularly over the last six years, in the field of hydrolase-catalyzed reactions integrated with chemical, electro-, and photocatalysis, emphasizing their emerging role in advanced synthetic methodologies.