Processes via Transamination

The synthesis of chiral a-amino acids starting from a-keto acids by means of a transamination has been reported by NSC Technologies [26, 27]. In this process, which can be used for the preparation of l- as well as D-amino acids, an amino group is transferred from an inexpensive amino donor, e.g., L-glutamic acid, l-22, or L-aspartic acid, in the presence of a transaminase (= aminotransferase). This reaction requires a cofactor, most commonly pyridoxal phosphate, which is bound to the transaminase. The substrate specificity is broad, allowing the conversion of numerous keto acid substrates under formation of the L-amino acid products with high enantioselectivities [28]. 

A typical example for an efficient transamination process is the production of l-alanine, l-25, which is carried out in a continuous manner starting from pyruvate, 24, and L-glutamate, l-22, with a high space-time yield of 4.8kg/(L-d) (Fig. 13) [28], In addition, several non-proteinogenic a-amino acids, e.g., L-phosphinothri-cine, L-homophenylalanine, and L-tert-leucine have been also produced via transamination. 

A drawback of many transaminations has been the limitation of the yields (around 50%) due to thermodynamic reasons [28, 29]. This problem of incomplete reactions has been solved by coupling the transamination reaction to another reac- 

In a recent optimization study, an alternative coupling system has been developed [29 c], The chemical yield in the synthesis of two non-proteinogenic a-amino acids was remarkably improved by applying a coupled transamination process using additionally an ornithine co-aminotransferase to couple L-ornithine co-trans-amination to L-glutamate a-transamination [29 c], 

A biocatalytic enantioselective addition of ammonia to a C=C bond of an afl-unsaturated compound, namely fumaric acid, makes the manufacture of L-aspar-tic acid, l-27, possible [30], This L-amino acid represents an important intermediate for the production of the artificial sweetener aspartame. The biocatalytic production process, which is applied on an industrial scale by, e.g., Kyowa Hakko Ko-gyo and Tanabe Seiyaku, is based on the use of an aspartate ammonia lyase [E.C.4.3.1.1] [31]. As a biocatalyst, an immobilized L-aspartate ammonia lyase from Escherichia coli [32, 33] as well as Brevibacterium flavum whole-cell catalysts [32 a, 34] have been applied successfully. 

---