Status of protein engineering for biocatalysts: how to design an industrially useful biocatalyst

Abstract

Recent advances in the development of both experimental and computational protein engineering tools have enabled a number of further successes in the development of biocatalysts ready for large-scale applications. Key tools are first, the targeting of libraries, leading to far smaller but more useful libraries than in the past, second, the combination of structural, mechanistic, and sequence-based knowledge often based on prior successful cases, and third, the advent of structurally based algorithms allowing the design of novel functions. Based on these tools, a number of improved biocatalysts for pharmaceutical applications have been presented, such as an (R)-transaminase for the synthesis of active pharmaceutical ingredients (APIs) of sitagliptin (Januvia®) and ketoreductases, glucose dehydrogenases, and haloalkane dehalogenases for the API synthesis toward atorvastatin (Lipitor®) and montelukast (Singulair®).