Advantages of Biocatalysis

To perform (large-scale) synthesis of drugs, materials, or chemicals, one can in principle follow three different approaches with various degrees of complexity  

Use a purely chemical strategy with classical organic reactions and/or new special reactions. 

Use a chemo-enzymatic route combining chemical and biocatalytic steps. In this case the biocatalyst is preferentially used to perform the key reaction(s) requiring high selectivity or specificity. 

Use a biological total synthesis by fermentation or multi step biotransformation (with growing cells, resting cells, multi-enzyme systems, genetically or metabolically engineered biocatalysts, etc). 

Enzymes and whole-cell biocatalysts have several properties that make them attractive for 

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Another advantage of biocatalysis is that chemo-, regio-, and stereoselectivities are attainable that are difficult or impossible to achieve by chemical means. A pertinent example is the production of the artificial sweetener, aspartame, which has become somewhat of an industrial commodity. The enzymatic process (Fig. 2.31), operated by the Holland Sweetener Company (a joint venture of DSM and Tosoh), is completely regio- and enantiospecific (Oyama, 1992). 

Further advantages of biocatalysis over chemical catalysis include shorter synthesis routes and milder reaction conditions. Enzymatic reactions are not confined to in vivo systems - many enzymes are also available as isolated compounds which catalyze reactions in water and even in organic solvents [28]. Despite these advantages, the activity and stability of most wild-type enzymes do not meet the demands of industrial processes. Fortunately, modern protein engineering methods can be used to change enzyme properties and optimize desired characteristics. In Chapter 5 we will outline these optimization methods, including site-directed mutagenesis and directed evolution. 

The production of single enantiomers of drug intermediates is increasingly important in the pharmaceutical industry. Biocatalysis provides organic chemists an alternate opportunity to prepare pharmaceutically important chiral compounds. The advantages of biocatalysis over chemical catalysis are that enzyme-catalyzed reactions are stereoselective and regioselective, and can be carried out at ambient temperature and atmospheric pressure providing an environmentally friendly system. The selective examples presented in this... 

The examples selected here are commercially relevant and focus on specific topics discussed above. They demonstrate the advantage of biocatalysis in the conversion of functional groups and configuration, resolution of racemates, and asymmetric synthesis. 

The large-scale resolution of racemic 2-alkanols to enantiomerically pure (R-)-and (S-t-)-alkanols by lipase shows environmental, health and safety advantages of biocatalysis compared with nonenzymatic syntheses. The biocatalytic Baeyer-Villi-ger oxidation of racemic bicyclo[3.2.0]-hept-2-en-6-one to enantiomerically pure 2-oxabicyclo[3.3.0]-oct-6-en-3-one and 3-oxabicyclo[3.3.0]-oct-6-en-2-one by CHMO represents an asymmetric Baeyer-Villiger oxidation. 

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