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The inclusion of an article in this document does not give any indication of safety or operability. Anyone wishing to use any reaction or reagent must consult and follow their internal chemical safety and hazard procedures and local laws regarding handling chemicals

*CMR = Carcinogenic, mutagenic, reprotoxic

General Overview

Enzymes are nature’s catalyst’s – made by cells to speed up reactions that sustain life.

  • Rate enhancements 108 –1014+ at 0.001 M or less
  • Macromolecules comprising a defined sequence of l-amino acids
  • 250-300+ units – molecular weight 30-90+ K daltons
  • Possibly associated with metals, cofactors, post –translational modification like glycosolation
  • Maybe monomeric, dimeric, aggregates with well defined, complex 3D structures
  • Typically active in aqueous systems, 20-40oC, pH 4 to 9
  • For biocatalysis, can be used as pure/semi-purified enzymes, mixtures, crude cell pastes and whole cells

Benefits of biocatalysis:

  • Highly stereo-, chemo- and regio-selective. (Often in nature, the enzyme may not catalyse a chiral process – but may well do with an unnatural substrate!)
  • Efficiency – has the potential for very high turnover numbers
  • Economics – simple whole cell reactions, or recovery and reuse of a supported, isolated enzyme
  • Will catalyse reactions under mild conditions; can use sensitive substrates
  • Potential for clean/green processes
  • May access reactions/selectivity that are difficult or impossible via chemical catalysis/synthesis
  • Positive safety and environmental considerations

There are several perceived drawbacks to using enzymes in chemical processes.

  • Esoteric
  • Small scale – mg’s
  • High cost
  • Lack of availability
  • Few enzymes available
  • Need microbiology/fermentation expertise
  • Enzymes do not accept unnatural substrates
  • Cannot be used with organic solvents
  • Need very dilute reactions
  • Cofactor recycling issues with redox enzymes

However today, there are many suppliers of enzymes and the ability to quickly evolve more robust and active bespoke enzymes for any particular process, annulling many of the shortcomings above. Enzymes can be found in many chemical processes across a wide range of industries.

  • Food Industry
  • Agrochemicals
  • Pharmaceuticals
  • Detergents
  • Fine chemicals
  • Leather/Textiles
  • Cosmetics
  • Oil/Biodiesel
  • Polymers
  • Diagnostics
  • Biosensors
  • Bioremediation
  • Wood pulp/paper recycle
  • Vitamins/Nutraceuticals

All enzymes can be subdivided into five main enzyme classes (EC). These classes are tabulated below along with typical reactions within each EC. This guide reviews a range of enzymes most typically used in organic synthesis.






Reduction of C=O, C=N, and C=C; reductive amination of C=O; oxidation of C-H, C=C, C-N, and C-O, cofactor reduction/oxidation



Transfer of functional groups such as amino, acyl, phosphoryl, methyl, glycosyl, nitro and sulfur-containing groups



Hydroylsis of esters, amides, lactones, lactams, epoxides, nitriles; reverse reactions to form esters, amides etc



Addition of small molecules to double bonds such as C=C, C=N, and C=O



Interconversion of isomers (isomerisations) such as racemisations, epimerisations, and rearrangement reactions



Formation of complex compounds (in analogy to lyases), enzymatically active only when combined with ATP cleavage


Green Criteria for Biocatalysis

  1. Solvents should be chosen to minimize any potential safety and environmental impact.
  2. Enzyme charge optimised
  3. Temperature/pH functions optimised
  4. Any substrate/product inhibition mitigated
  5. Issues with any unfavourable equilibrium solved
  6. Correct/sufficient cofactor present? Sufficient H2 equivalents for efficient cofactor recycling
  7. Need to consider the impact of mixing on enzyme stability—sheer, grinding of polymer resins, etc., foaming, and possible interfacial deactivation
  8. Is mass transfer an issue? —Certainly, for oxidations which typically require the introduction of some of air/oxygen gas


General Literature Reviews on Biocatalysis

Chapman, J.; Ismail, A. E.; Dinu, C. Z. Industrial Applications of Enzymes: Recent Advances, Techniques, and Outlooks. Catalysts 2018, 8 (6), 238.

Sheldon, R. A.; Woodley, J. M. Role of Biocatalysis in Sustainable Chemistry. Chem. Rev., 2018, 118, 801–838.

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

Adams, J. P.; Brown, M. J. B.; Diaz-Rodriguez, A.; Lloyd, R. C.; Roiban, G.-D. Biocatalysis: A Pharma Perspective. Adv. Synth. Catal. 2019, 362, 2421–2432

Green, A. P.; Turner, N. J. Biocatalytic retrosynthesis: Redesigning synthetic routes to high-value chemicals. Perspectives Sci. 2016, 9, 42–48.

Patel, R. N. Biocatalysis for synthesis of pharmaceuticals. Bioorg. & Med. Chem. 2018, 26 (7), 1252–1274.

Rosenthal, K.; Lütz, S. Recent developments and challenges of biocatalytic processes in the pharmaceutical industry. Curr. Opin. Green Sust. 2018, 11, 58–64.

Hughes, D. L. Biocatalysis in Drug Development – Highlights of the Recent Patent Literature. Org. Process Res. Dev. 2018, 22, 1063–1080.

Hönig, M.; Sondermann, P.; Turner, N. J.; Carreira, E. M. Enantioselective Chemo- and Biocatalysis: Partners in Retrosynthesis. Angew. Chem. Int. Ed. 2017, 56, 8942–8973.

Dong, J.; Fernández-Fueyo, E.; Hollmann, F.; Paul, C. E.; Pesic, M.; Schmidt, S.; Wang, Y.; Younes, S.; Zhang, W.  Biocatalytic Oxidation Reactions: A Chemist’s Perspective. Angew. Chem. Int. Ed. 2018, 57, 9238–9261.

Grogan, G. Synthesis of chiral amines using redox Biocatalysis. Curr. Opin Chem. Biol. 2018, 43, 15–22.

Sheldon, R. A.; Pereira, P. C. Biocatalysis engineering: the big picture. Chem. Soc. Rev. 2017, 46, 2678–2691.

Turner, N. J.; O-Reilly, E. Biocatalytic retrosynthesis. Nat. Chem. Bio. 2013, 9, 285–288.

Woodley, J. M. Accelerating the implementation of biocatalysis in industry. Appl. Microbiol. Biotechnol. 2019, 103, 4733–4739.

Flow Biocatalysis
Britton, J.; Majumdar, S.; Weiss, G. A. Continuous flow biocatalysis.  Chem. Soc. Rev. 2018, 47, 5891–5918.

Thompson, M. P.; Peñafiel, I.; Cosgrove, S. C.; Turner, N. J. Biocatalysis Using Immobilized Enzymes in Continuous Flow for the Synthesis of Fine Chemicals. Org. Process Res. Dev. 2019, 23, 9–18.

Shi, J.; Wu, Y.; Zhang, S.; Tian, Y.; Yang, D.; Jiang, Z. Bioinspired construction of multi-enzyme catalytic systems. Chem. Soc. Rev. 2018, 47, 4295–4313.

Schrittwieser, J. H.; Velikogne, S.; Hall, M.; Kroutil, W. Artificial Biocatalytic Linear Cascades for Preparation of Organic Molecules. Chem. Rev. 2018, 118, 270−348.

Sperl, J. M.; Sieber, V. Multienzyme Cascade Reactions—Status and Recent Advances. ACS Catal. 2018, 8, 2385−2396.