Streamlining Design, Engineering, and Applications of Enzymes for Sustainable Biocatalysis

In this Perspective we show how an expansion of the scope and impact of biocatalysis in industrial organic synthesis is enabled by streamlining the underpinning biocatalyst and bioprocess engineering. We begin by discussing how the underlying need for waste reduction and high (enantio)selectivities fostered the introduction of biocatalysis as a sustainable technology for the industrial synthesis of active pharmaceutical ingredients (APIs). We continue by showing how advances in molecular biology, in particular gene sequencing and protein engineering, enabled the development of more and better enzymes, thereby broadening the industrial scope of biocatalysis. Further process improvements are provided through protein engineering for enzyme immobilization and integration of enzyme production with in vivo immobilization. Finally, the use of immobilized enzymes in continuous operation (biocatalysis in flow) facilitates the sequential integration of multi-step reactions into enzymatic or chemo-enzymatic cascade processes, thus enabling the complete, cost-effective, and environmentally attractive production of APIs.