Stereospecific synthesis of amino acids

All of the established industrial processes which use enzymes are simple. The majority are hydrolyses where one substrate, water, is the solvent. A few reactions of greater complexity, such as the synthesis of L-tryptophan from indole and L-serine, are described in patents, but it is by no means clear that these are viable commercial processes. A few complex reactions have been taken to the scale of a large pilot plant, one of these being the stereospecific synthesis of a few amino acids from racemic a-hydroxyacids. This must complete with other processes for the manufacture of amino acids, but it does already operate at a tonne scale. 

The coupling of an oxidation and a reduction stage through NAD recycles the cofactor, just as does Saccharomyces cerevisiae in the synthesis of ethanol (see section 6.2.1.1). Without such coupling each half of the reaction would be limited by the concentration of NAD and this is a general problem which must be faced in the development of many synthetic reactions. 

The catalytic reactor thus consists of an ultrafiltration cell containing the enzymes and their cofactor. Substrates diffuse into the cell across the membrane, and the amino acids diffuse back. The substrate stream would eventually reach an equilibrium containing a mixture of hydroxyacids, ketoacids and amino acids were it not for the removal of the amino acids with a cation exchange resin. 

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Extensive research on characteristics and structure of amino acid dehydrogenases reflects their usefulness for application in industry and other fields. In particular, L-amino acids, which are substrates in oxidative deamination and products in reductive amination, are a very important nutrient, and are also starting materials in pharmaceutical compounds. Amino acid dehydrogenases have been used for the stereospecific synthesis of amino acids from achiral substrates, 2-oxo acids, and ammonia, and for analysis of L-amino acids, oxo acids, ammonia, and assay of enzymes of which amino acids and oxo acids are their substrates or products. Some applications of amino acid dehydrogenases are described in this section. 

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