Tailor-made enzyme

J. Gante, Peptide mimetics—tailor-made enzyme inhibitors, Angew. Chem. Int. Ed. 33(1994) 1699-1720. 

When comparing chemical and biocatalytic methods, one could say that, especially for asymmetric oxidations, enzymatic methods enter the scene. This is most evident in the area of asymmetric Baeyer-Villiger oxidation, where biocatalysts take the lead and homogeneous chiral catalysts lag far behind in terms of ee values. Significant progress can be expected in the area of biocatalysis due to the advancement in enzyme production technologies and the possibility of tailor-made enzymes. 

The examples provided in this Chapter demonstrate that directed evolution resembles a very useful tool to create enzyme activities hardly accessible by means of rational protein design (Table 14.1). Even if the desired substrate specificity is known from other biocatalysts - e.g. phospholipase A1 activity - the advantage of the directed evolution approach resides in the already achieved functional expression of a particular protein. Thus bottlenecks arising from the identification of enzymes by traditional screening and cultivation methods can be circumvented. In addition, directed evolution can dramatically reduce the time required for the provision of a suitable tailor-made enzyme, also because cloning and functional expression of the biocatalyst has already been achieved. 

Tailor-Made Enzymes - Catalytic Antibodies There are antibodies that catalyze reactions by mimicking their transition states. A catalytic antibody can be regarded as a tailor-made artificial enzyme. 

They offer a unique access to artificial tailor-made enzyme-like catalysts and are able to catalyze reactions which have no equivalent counterpart within the diverse natural enzymes. 

From a synthetic standpoint, the major drawback to this dass of enzymes is their rdativdy narrow range of acceptable substrates. With very few exceptions, they require an a-keto add substrate. Recent protein engineering efforts by Bommar-ius have overcome this limitation, raising the prospert of tailor-made enzymes for asymmetric reductive amination [7]. This solves a key unmet need in synthesis and details are covered in a later chapter (Figure 1.11). 

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