Synthetic toolbox: Biocatalysis

Summary and further reading

In this module we have seen that many enzymes can be applied in biocatalytic retrosynthetic analysis, and it is important that this is applied more often in route design, combining bio and chemo-catalysts to design new routes to target molecules.  To achieve this there are some remaining challenges in the field, including the identification of reactions not available in the enzyme tool box and the design of new biocatalysts with broad substrate scope, that are highly active and stable under chemical process conditions, via the combination of enzyme engineering with bioinformatic methods.

Recommended reading:

A. S. Wells, Biocatalysis for Medicinal Chemistry, in Green and Sustainable Medicinal Chemistry: Methods, Tools and Strategies for the 21st Century Pharmaceutical Industry, The Royal Society of Chemistry, 2016, ch. 15, pp. 180-191.

C. M. Clouthier and J. N. Pelletier, Expanding the organic toolbox: a guide to integrating biocatalysis in synthesis, Chem. Soc. Rev., 2012, 41, 1585-1605.

G. W. Huisman and S. J. Collier, On the development of new biocatalytic processes for practical pharmaceutical synthesis, Curr. Opin. Chem. Biol., 2013, 17, 284-292.

Enzyme Catalysis in Organic Synthesis, (ed. H. Gröger and O. May) Wiley-VCH Verlag GmbH & Co. KGaA, 2012.

Biocatalysis in Organic Synthesis, Science of Synthesis (ed. W. - D. Fessner and N. J. Turner) vol. 1, 2015.

K. Faber, Biotransformation in Organic Chemistry, Springer Verlag, Sixth., 2011.

S. Warren and P. Wyatt, Organic Synthesis: The Disconnection Approach, John Wiley and Sons, 2008.

N. J. Turner and E. O'Reilly, Biocatalytic retrosynthesis, Nat Chem Biol, 2013, 9, 285-288.

M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Keßeler, R. Stürmer and T. Zelinski, Industrial Methods for the Production of Optically Active Intermediates, Angew. Chem. Int. Ed., 2004, 43, 788-824.

B. M. Nestl, S. C. Hammer, B. A. Nebel and B. Hauer, New Generation of Biocatalysts for Organic Synthesis, Angew. Chem. Int. Ed., 2014, 53, 3070-3095.

U. T. Bornscheuer, G. W. Huisman, R. J. Kazlauskas, S. Lutz, J. C. Moore and K. Robins, Engineering the third wave of biocatalysis, Nature, 2012, 485, 185-194.

H. Gröger and W. Hummel, Combining the ‘two worlds’ of chemocatalysis and biocatalysis towards multi-step one-pot processes in aqueous media, Curr. Opin. Chem. Biol., 2014, 19, 171-179.