Transamination decarboxylation spontaneous

The procedure reported in Scheme 13.11 describes deracemization of an amino acid involving oxidation with an L-specific enzyme and transamination with a D-amino transferase using D-aspartate 10, which is generated from L-aspartate 11 by aspartate racemase, as the amino donor. The oxidative enzyme is defined as an L-amino acid deaminase, a flavoprotein from Proteus myxofadens [34]. The transamination reaction is shifted towards the product since the oxalacetate 12 formed decarboxylates spontaneously to give pyruvate and carbon dioxide. 

Kumagai and coworkers11131 developed an enzymatic procedure to produce d-alanine from fumarate by means of aspartase (E. C. 4.3.1.1), aspartate racemase, and D-amino acid aminotransferase (Fig. 17-12). Aspartase catalyzes conversion of fumarate into L-aspartate, which is racemized to form D-aspartate. D-Amino acid aminotransferase catalyzes transamination between D-aspartate and pyruvate to produce D-alanine and oxalacetate. This 2-oxo acid is easily decarboxylated spontaneously to form pyruvate in the presence of metals. Thus, the transamination proceeds exclusively toward the direction of D-alanine synthesis, and total conversion of fumarate into D-alanine was achieved. 

Although the utility of transaminases has been widely examined, one such limitation is the fact that the equilibrium constant for the reaction is near unity. Therefore, a shift in this equilibrium is necessary for the reaction to be synthetically useful. A number of approaches to shift the equilibrium can be found in the literature.53 124135 Another method to shift the equilibrium is a modification of that previously described. Aspartate, when used as the amino donor, is converted into oxaloacetate (32) (Scheme 19.21). Because 32 is unstable, it decomposes to pyruvate (33) and thus favors product formation. However, because pyruvate is itself an a-keto acid, it must be removed, or it will serve as a substrate and be transaminated into alanine, which could potentially cause downstream processing problems. This is accomplished by including the alsS gene encoding for the enzyme acetolactate synthase (E.C. 4.1.3.18), which condenses two moles of pyruvate to form (S)-aceto-lactate (34). The (S)-acetolactate undergoes decarboxylation either spontaneously or by the enzyme acetolactate decarboxylase (E.C. 4.1.1.5) to the final by-product, UU-acetoin (35), which is meta-bolically inert. This process, for example, can be used for the production of both l- and d-2-aminobutyrate (36 and 37, respectively) (Scheme 19.21).8132 136 137... 

An innovative approach to cephalosporin C and 7ACA recovery involves the enzymatic conversion of cephalosporin C to solvent extractable intermediates and ultimately to 7ACA. The first step involves microbial deamination or chemical transamination to the a-ketoadipyl or, after spontaneous decarboxylation, glutaryl cephalosporin C derivatives (51-54). These derivatives then—unlike cephalosporin C itself--can be enzymatically cleaved to 7ACA (55-60). These reactions are shown in Figure IS. 

One approach to this problem is the coupling of the transamination reaction to a second reaction that consumes the keto acid by product in an essentially irreversible step this drives the transamination reaction to completion. By using an aminotransferase that can utilize aspartic acid efficiently as the amino group donor (instead of glutamic acid), the corresponding 2-keto acid by product is oxaloacetate (rather than 2-ketoglutarate). Oxaloacetate is a (3-ketoacid and can be easily decarboxylated to pyruvate. This decarboxylation occurs spontaneously in aqueous solution, catalyzed... 

Imidazolone propionate hydrolase catalyzes the enzymatic cleavage of the imidazole ring to yield formi-minoglutamate. The rat liver enzyme has been partially purified. In addition to the enzymic conversion, two nonenzymic spontaneous reactions yield N-formyl-isoglutamine and 4-oxoglutamic acid. In addition to the oxidative pathways for histidine, there exist three other pathways for its use protein synthesis, decarboxylation to yield histamine (see Inflammation), and transaminase. The activity of histidine pyruvic transamination in rat liver is three times that of histidase. The product of the transaminase reaction is imidazole pyruvic acid, which in turn is converted to imidazole acetic acid. 

Kynurenic acid and xanthurenic acid, side products of the reaction, are the products of the transamination of the a-amino group of kynurenine and 3-hydroxy-kynurenine to a-ketoglutaric acid in the presence of pyridoxal phosphate and an enzyme found in mammalian liver and kidney, kynurenine transaminase. The keto acid resulting from the transamination reaction condenses spontaneously. Liver homogenate also decarboxylates 3-hydroxykynurenine to yield 4,8-de-hydroxyquinoline. Kynurenase may catalyze the cleavage of the side chain of kynurenine or 8-hydroxy-kynurenine and lead to the formation of alanine and... 

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