Expanding biocatalytic reactivity landscapes by physical fields and chemical strategies for green manufacturing

The burgeoning demand for green manufacturing has spurred significant interest in harnessing biocatalysis across diverse sectors for the synthesis of high value-added compounds. Despite the inherent utility of biocatalysts, their application is often circumscribed by the specificity of the natural enzymes involved. To transcend these limitations, innovative physical and chemical methodologies have been integrated into biocatalytic processes. Physical field interventions, such as the application of mechanical force (force), temperature (heat), light, electricity, and ultrasound (sound) have been employed to engineer reaction systems that facilitate the transformation of substrates into target compounds. On the chemical frontier, metal catalysis, small molecule organocatalysis coupled with biocatalysis in cascade reactions have been revolutionized through several strategies: (I) the one-pot approach, where products are isolated in a stepwise manner by the metal catalysis and biocatalysis; (II) the sequential cascade reaction within a single vessel, wherein enzymes and metal catalysts are introduced simultaneously to amplify product yield; and (III) the cooperative reaction paradigm, where the metal catalyst's product serves as an intermediate or substrate that synergistically interacts with the enzyme to yield the desired product in a one-pot synthesis. This review outlines the research progress in physical and chemical techniques in biocatalysis, aiming to further broaden the reactivity profile of natural enzymes and thereby produce more desired chemicals in past years.