Bienzymatic System for P-Amino Acid Production

Recent results on the use of dihydropyrimidinase/p-carbamoylase cascade demonstrate that it constitutes an interesting biotechnological tool allowing the total conversion of the natural substrates DHU and 5-METDHU into p-alanine and a-methyl-P-alanine (3-AiBA). Additionally, a-phenyl-P-alanine has been produced from its DHU derivatives. Both p-alanine derivatives were produced enantioen-riched as (R)-a-phenyl-P-alanine (ee 95%) and (R)-a-methyl-P-alanine (3-AiBA) (ee 90%) [44]. Analytical experiments with the tandem enTymes at high substrate concentration provide evidence of total conversion without noticeable inhibition effect Thus, when 100 mM and 1 M solutions of 5-METDHU were hydrolyzed and transformed totally into 3-AiBA, the former first reaction concentration required a similar period of time as was observed in the small-scale experiment, while the latter took only slightly longer. 

Juaristi, E. and Lopez-Ruiz, H. (1999) Recent advances in the enantioselective synthesis of p-amino acids. Curr. Med. Chem., 6 (10), 983-1004. 

Weiner, B., Szymanski, W., Janssen, D.B., Minnaard, A.J., and Feringa, B.L (2010) Recent advances in the catalytic asymmetric synthesis of P-amino acids. Chem. Soc. Rev., 39 (5), 1656-1691. 

Magriotis, P.A. (2001) Recent progress in the enantioselective synthesis of beta-lactams development of the first catalytic approaches. Angew. Chem. Int. Ed., 40 (23), 4377-4379. 

Cronan, J.E., Little, K.J., and Jackowski, S. (1982) Genetic and biochemical analyses of pantothenate biosynthesis in Escherichia coli and Salmonella typhimurium. J. Bacterid., 149 (3), 916-922. 

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