Biocatalysis – A Gateway to Industrial Biotechnology

1 The use of biocatalysts, both as enzymes and also engineered whole cells, in the manufacture of chemicals offers major advantages in terms of enhanced reaction selectivity, reduced cost of raw materials, lower energy costs, improved safety and importantly sustainability of production. Research groups in both academic institutions and particularly in industry are increasingly embracing biocatalysis as a tool for the synthesis of a broad range of molecules which traditionally have been prepared using chemical processes. Although the focus of most of the papers in this special issue is (chiral) pharmaceutical building blocks, biocatalysis is now being applied more broadly in the manufacture of ingredients for personal health-care products, polymers, agrochemicals, fine chemicals and fuel molecules. The field of synthetic biology is offering the prospect of engineering cells containing multiple genes that allow the conversion of simple biomass-derived starting materials into high value products via multi-step transformations. In the pharmaceutical industry, there have been some recent important developments in the application of biocatalysis in 2nd generation manufacturing processes in which chemical processes for the manufacture of a drug are replaced by new, lower cost, biotechnology-based approaches. The future is likely to see further uptake of biocatalysis, particularly if the process development times can be reduced to levels where biocatalysis can be considered as the method of choice for 1st generation manufacturing processes. In order to introduce step-changes into the ways in which future biocatalysts are developed it will be necessary to develop new technologies for both the rapid evolution of enzymes and also the construction of engineered whole cells in the laboratory. A key challenge is the integration of a range of enabling methods, particularly high-throughput screening and library design, combined with structure-guided rational re-engineering of proteins by use of X-ray and informatics data, in order to reduce the timeline required for evolutionary optimisation of enzymes. The laboratory evolution platforms of the future will be applied to the development of industrial biocatalysts that are ‘fit-for-purpose’ in processes that can be rapidly taken from the laboratory to large scale manufacture. Another critical challenge for the biocatalysis community, particularly in academe, is to broaden the range of biocatalysts in the toolbox. During the past 10–20 years, certain classes of enzymes, e.g., lipases, esterases, nitrilases, ketoreductases, aldolases etc. have been developed to the point where they are now used on a fairly routine basis for practical applications. More recently other enzyme classes have begun to emerge, e.g., transaminases and enoate reductases. The successes have merely highlighted the need for an even greater range of biocatalysts in the future and hence attention is turning to other hydrolytic (e.g., dehalogenases) enzymes and those for CC (e.g., lyases) and CN (ammonia lyases) bond construction as well as enzymes for oxidations under environmentally benign conditions (e.g., P450 monooxygenases, oxidases, haloperoxidases). Researchers are also exploring new ways of combining enzymes in cascade processes that promise to improve the overall economy of multi-step conversions and also combining bio- and chemo-catalysts to introduce efficient deracemisation and dynamic kinetic resolution procedures. The 31 papers in this special issue of Advanced Synthesis and Catalysis address many of the important contemporary themes which are currently driving the development of biocatalysis. Some papers provide timely reviews of the state-of-the-art whereas others focus on specific themes and new reaction types. All of the papers contained herein will contribute to raise awareness in this field and drive forward future developments in biocatalysis.