Amino Acid Dehydrogenase-Catalyzed Processes

In contrast, amino acid dehydrogenases comprise a well-known class of enzymes with industrial apphcations. An illustrative example is the Evonik (formerly Degussa) process for the synthesis of (S)-tert-leucine by reductive amination of trimethyl pyruvic acid (Scheme 6.12) [27]. The NADH cofactor is regenerated by coupling the reductive amination with FDH-catalyzed reduction of formate, which is added as the ammonium salt. 

An elegant four-enzyme cascade process was described by Nakajima et al. [28] for the deracemization of an a-amino acid (Scheme 6.13). It involved amine oxidase-catalyzed, (i )-selective oxidation of the amino acid to afford the ammonium salt of the a-keto acid and the unreacted (S)-enantiomer of the substrate. The keto acid then undergoes reductive amination, catalyzed by leucine dehydrogenase, to afford the (S)-amino acid. NADH cofactor regeneration is achieved with formate/FDH. The overall process affords the (S)-enantiomer in 95% yield and 99% e.e. from racemic starting material, formate and molecular oxygen, and the help of three enzymes in concert. A fourth enzyme, catalase, is added to decompose the hydrogen peroxide formed in the first step which otherwise would have a detrimental effect on the enzymes. 

A cartoon representation of the oxidation path used in Equation 9.5 is shown in Scheme 9.5. The process is catalyzed by the enzyme glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). A large body of evidence has been accumulated about the role of the enzyme and, in particular, that the catalytic site on the enzyme that is used to help the oxidation occur bears a thiol (-SH, Chapter 8) group (from the amino acid cysteine. Chapter 12). Further, it has been shown that hydride (H ) transfer to nicotinamide dinucleotide (NAD ") (see Chapter 12), a required cofactor that accounts for the transfer of the hydride anion and, thus, the oxidation itself, is also involved. 

---