Abstract
The pharmaceutical industry, driven by an increasing need to deliver new and more effective medicines to patients, is increasingly turning to the use of engineered biocatalysts for both lead generation of active compounds and the sustainable manufacture of active pharmaceutical ingredients. Advances in enzyme discovery, high-throughput screening and protein engineering have substantially expanded the available biocatalysts, and consequently, many more synthetic transformations are now possible. Enzymes can be fine-tuned for practical applications with greater speed and likelihood of success than before, thereby leading to greater predictability and confidence when scaling up these processes. Coupled with a greater awareness of which reactions are suitable for biocatalysis (for example, biocatalytic retrosynthesis), new chemoenzymatic and multi-enzyme processes have been designed and applied to the synthesis of a range of important pharmaceutical target molecules. Increasingly, researchers are exploring opportunities for using immobilized biocatalysts in flow conditions. In this Review, we discuss some of the key drivers and scientific developments that are expanding the application of biocatalysis in the pharmaceutical industry and highlight potential future developments that likely will continue to increase the impact of biocatalysis in drug development.
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Acknowledgements
N.J.T. acknowledges the European Research Council (ERC) for the award of an Advanced Grant.
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Nature Reviews Chemistry thanks J. Janey and the other anonymous reviewer(s) for their contribution to the peer review of this work.
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Glossary
- Metagenomics
-
The genome-wide sequencing of organisms in environmental samples.
- Directed evolution
-
An iterative process involving the mutagenesis of a gene and screening for or selection of protein variants that have the activity of interest.
- Parallel medicinal chemistry
-
(PMC). A routinely used technique for generating libraries of isolated targets from sets of monomers undergoing the same chemistry in parallel.
- Biologics
-
Pharmaceutical drug products or mixtures of compounds that are partially or entirely manufactured in a living organism and are often complex molecules of incompletely defined structure.
- Warhead
-
The cytotoxic drug in an antibody–drug conjugate.
- Linker
-
A chemical moiety that connects the antibody to the warhead in an antibody–drug conjugate.
- Continuous flow
-
Carrying out a number of chemical processes in a continuous flowing stream.
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Devine, P.N., Howard, R.M., Kumar, R. et al. Extending the application of biocatalysis to meet the challenges of drug development. Nat Rev Chem 2, 409–421 (2018). https://doi.org/10.1038/s41570-018-0055-1
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DOI: https://doi.org/10.1038/s41570-018-0055-1
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