Abstract

Cascade reactions have been described as efficient and universal tools, and are of substantial interest in synthetic organic chemistry. This review article provides an overview of the novel and recent achievements in enzyme cascade processes catalyzed by multi-enzymatic or chemoenzymatic systems. The examples here selected collect the advances related to the application of the sequential use of enzymes in natural or genetically modified combination; second, the important combination of enzymes and metal complex systems, and finally we described the application of biocatalytic biohybrid systems on in situ catalytic solid-phase as a novel strategy. Examples of efficient and interesting enzymatic catalytic cascade processes in organic chemistry, in the production of important industrial products, such as the designing of novel biosensors or bio-chemocatalytic systems for medicinal chemistry application, are discussed

Highlights

  • Cascade reactions, typically defined as a consecutive series of chemical reactions proceeding in a concurrent fashion, have attracted the research community’s attention in the last few years.One of the main areas where this strategy plays a pivotal role is in nature, with the biosynthesis of natural products [1,2].Systems where different enzymes, homogeneous organometallic complexes, are combined successively in a one-pot or tandem processes, in different manners, have been described as successful catalysts in different chemical applications [3,4].These processes present advantages when compared to the typical single reaction, such as atom economy, step-saving, and high yield and efficiency of the chemical process [5,6]

  • We focus this review article on the most recent advances achieved in the development and application of multi-enzymatic systems, based on three different approaches: enzymatic cascade systems, chemoenzymatic cascades, or a third strategy based on multi-enzymatic cascade on solid phase (Figure 1)

  • Multi-enzyme cascades, from two to nine different enzymes working in one-pot to obtain a final product in a more effective way

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Summary

Introduction

Typically defined as a consecutive series of chemical reactions proceeding in a concurrent fashion, have attracted the research community’s attention in the last few years. Homogeneous organometallic complexes, are combined successively in a one-pot or tandem processes, in different manners, have been described as successful catalysts in different chemical applications [3,4]. These processes present advantages when compared to the typical single reaction, such as atom economy, step-saving, and high yield and efficiency of the chemical process [5,6]. The use of enzymes as catalysts, conforming the cascade system, leads to a more sustainable and environmentally benign process These systems have some disadvantages, such as the fact that the enzymes have different pH and optimum temperatures, so it is necessary to develop strategies that exceed these requirements. We focus this review article on the most recent advances achieved in the development and application of multi-enzymatic systems, based on three different approaches: enzymatic cascade systems, chemoenzymatic cascades, or a third strategy based on multi-enzymatic cascade on solid phase (Figure 1)

Enzymatic Cascade Processes
Glyco-Enzymes
Cascade Enzymes in Aminoacid Chemistry
Chemo-Enzymatic Cascades
Solid-Phase Multi-Chemoenzymatic Cascade Reactions
Findings
Concluding Remarks
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