Biocatalysis: landmark discoveries and applications in chemical synthesis.

Biocatalysis has become an important tool in chemical synthesis, allowing access to complex molecules with high levels of activity and selectivity and with low environmental impact. Key discoveries in protein engineering, bioinformatics, recombinant technology and DNA sequencing have contributed towards the rapid acceleration of the field. This tutorial review explores enzyme engineering strategies and high-throughput screening approaches that have been applied for the discovery and development of enzymes for synthetic application. Landmark developments in the field are discussed and have been carefully selected to highlight the diverse synthetic applications of enzymes within the pharmaceutical, agricultural, food and chemical industries. The design and development of artificial biocatalytic cascades is also examined. This tutorial review will give readers an insight into the landmark discoveries and milestones that have helped shape and grow this branch of catalysis since the discovery of the first enzyme.

Strategies for designing biocatalysts with new functions.

The engineering of natural enzymes has led to the availability of a broad range of biocatalysts that can be used for the sustainable manufacturing of a variety of chemicals and pharmaceuticals. However, for many important chemical transformations there are no known enzymes that can serve as starting templates for biocatalyst development. These limitations have fuelled efforts to build entirely new catalytic sites into proteins in order to generate enzymes with functions beyond those found in Nature. This bottom-up approach to enzyme development can also reveal new fundamental insights into the molecular origins of efficient protein catalysis. In this tutorial review, we will survey the different strategies that have been explored for designing new protein catalysts. These methods will be illustrated through key selected examples, which demonstrate how highly proficient and selective biocatalysts can be developed through experimental protein engineering and/or computational design. Given the rapid pace of development in the field, we are optimistic that designer enzymes will begin to play an increasingly prominent role as industrial biocatalysts in the coming years.