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Introduction to Enzyme Catalysis and Biocatalytic Retrosynthesis

Biocatalysis can present a number of advantages including reduced cost of goods, improved environmental impact, better safety profiles, improved step and atom economy and reduced solvent usage, all of which can contribute to more sustainable manufacturing processes.  A major development in the field of biocatalysis is the impact that protein engineering and directed evolution have made on the properties of biocatalysts.  Another, relatively new concept is that of designing new synthetic routes to targte molecules using  ‘biocatalytic retrosynthesis’.  With biocatalytic retrosynthesis, molecules are disconnected in a different way than if solely chemical reagents are relied upon leading to the development of new pathways and new ways of making molecules.

What is biocatalytic retrosynthesis?

E. J. Corey pioneered retrosynthetic analysis in organic molecules: the process of ‘deconstructing’ a target molecule into readily available starting materials. [1]  Now, with biocatalysis surging and rightly staking a claim to be a viable option for chemical synthesis, we need to rethink the way in which target molecules can be constructed with the assistance of enzymes. ‘Biocatalytic retrosynthesis’ has potential as a construction and optimisation methodology and is becoming increasingly important for biochemical pathway design and generation.

Very few organic textbooks include enzyme-catalyzed reactions as options for synthesis during retrosynthetic analysis.  The potential impact of enzymes in the synthesis of complex molecules has not been fully realised

The following reference provides an excellent overview of biocatalytic retrosynthesis:

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

Categorisation of enzymes

In this video, Bettina Nestl introduces the six major enzyme classes and the types of reactions that can be performed by them.

Mechanism of enzyme catalysis

In this video, Bettina Nestl explains the four major mechanisms of enzyme catalysis.

Individual enzyme classes

In this video, Bettina Nestl goes through the individual enzymes classes in turn and looks in more detail at some of the reactions that can be catalysed by them.

  1. E. James Corey, The Logic of Chemical Synthesis: Multistep Synthesis of Complex Carbogenic Molecules (Nobel Lecture), Angew. Chem., Int. Ed. Engl., 1991, 30, 455-465.