Pharmaceuticals via Biotransformation

Biotransformations are chemical reactions that are induced by enzymes in the cells. Sometimes it is possible to isolate the enzymes and to carry out the chemical reaction in a separate reactor in the absence of living cells. Starting materials are single chemical compounds or mixtures of related compounds, which are converted to the product with high selectivity. Specificity has several levels Conversion of one compound in a mixture of similar compounds or conversion of only one functional group on a complex molecule with many functional groups. 

Many biotransformations are difficult to achieve by conventional synthesis. A classical example is the synthesis of chiral molecules. 

A compound is chiral when it can occur in two forms that are mirror images of each other. The two forms (enantiomers) are very similar, hut not identical, for instance, like the right and the left hand of the same person. Classical synthesis produces both enantiomers in a 1 to 1 ratio. They cannot he separated hy normal physical means. Nature is, however, more selective. Here, only single enantiomers are formed. This can he used to separate D,L enantiomers of amino acids. The enzyme L-amylase produces selectively the L-amino acid from a mixture of the DL-acylamino acids. The D-acylamino acid remains unchanged and can he separated easily hy extraction or crystallization. 

Separation of enantiomers is important in the pharmaceutical industry, because often only one enantiomer has the desired efficacy, whereas the other causes unwanted side effects. 

It is also possible to convert nonchiral readily available industrial organic chemicals into valuable chiral natural-analogue products. This is demonstrated by the conversion of achiral fumaric acid to L(-)-malic acid with fumarase as the active enzyme. The same compound is converted to the amino acid L(-h)-aspartic acid by Escherichia bacteria that contain the enzyme aspartase. If pseudomonas bacteria are added, another amino acid L-alanine is formed (Eq. 9.10). 

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