Phenylalanine dehydrogenase PDH

Allysine ethylene acetal is synthesized from the corresponding keto acid by reductive amination using phenylalanine dehydrogenase (PDH) from Thermoacti-nomyces intermedius ATCC 33205 combined with FDH from C. boidinii SC13822 for the regeneration of NADH (Fig. 39). 

Fig. 39 Conversion of 5-(l,3-dioxolan-2-yl)-2-oxo-pentanoid acid to allysine ethylene acetal by reductive amination using phenylalanine dehydrogenase (PDH) and formate dehydrogenase (FDH) for cofactor recycling...

Enzymatic Synthesis of At lysine Ethylene Acetal. (S)-2-Amino-5-(l,3-dioxolan-2-yl)-pentanoic acid (5 )-allysine ethylene acetal (7) (Fig. 3A) is one of three building blocks used in an alternative synthesis of Omapatrilat (1). It previously had been prepared via an eight-step chemical synthesis from 3,4-dihydro [2H] pyran (16). An alternate synthesis of (7) was demonstrated by reductive amination of ketoacid acetal (8) using phenylalanine dehydrogenase (PDH) from Thermoactinomyces intermedins (17). The reaction required ammonia and NADH NAD produced during the reaction was recycled to NADH by the oxidation of formate to CO using formate dehydrogenase (FDH). 

T. intermedins IFO14230 (ATCC 33205) was first identihed as a source of PDH by Ohshima et al." The enzyme was purified and characterized" and then cloned and expressed in E. coli by the same workers. The enzyme was reported to be moderately specihc for deamination of phenylalanine and to carry out the amination of some keto acids at a much lower rate than amination of phenylpyruvate." In our screening, the enzyme was the most effective amino acid dehydrogenase identified for the reductive amination of the keto acid acetal. 

Fig. 8. From chorismate to phenylalanine and tyrosine. (PDHY = prephenate dehydratase EC 4.2.1.51 PDH = prephenate dehydrogenase EC 1.3.1.13 TAT = tyrosine aminotransferase EC 2.6.1.5 PREPAT = prephanate aminotransferase PTDH = pretyrosine dehydrogenase.)...

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