7. Synergies of Chemistry and Biochemistry for the Production of β-Amino Acids

  1. Sergio Riva2 and
  2. Wolf-Dieter Fessner3
  1. Josefa María Clemente-Jiménez,
  2. Sergio Martínez-Rodríguez,
  3. Felipe Rodríguez-Vico and
  4. Francisco Javier Las Heras-Vázquez

Published Online: 27 JUN 2014

DOI: 10.1002/9783527682492.ch7

Cascade Biocatalysis : Integrating Stereoselective and Environmentally Friendly Reactions

Cascade Biocatalysis : Integrating Stereoselective and Environmentally Friendly Reactions

How to Cite

Clemente-Jiménez, J. M., Martínez-Rodríguez, S., Rodríguez-Vico, F. and Las Heras-Vázquez, F. J. (2014) Synergies of Chemistry and Biochemistry for the Production of β-Amino Acids, in Cascade Biocatalysis : Integrating Stereoselective and Environmentally Friendly Reactions (eds S. Riva and W.-D. Fessner), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527682492.ch7

Editor Information

  1. 2

    Istituto di Chimica del, Riconoscimento Molecolare, C. N. R., Via Mario Bianco 9, 20131 Milano, Italy

  2. 3

    Technische Universität, Darmstadt, Department of Organic, Chemistry and Biochemistry, Petersenstr. 22, D-64287 Darmstadt, Germany

Author Information

  1. Universidad de Almería, Departamento de Química-Física, Carretera de Sacramento S/N, Edificio C.I.T.E. I, La Cañada de San Urbano, 04120, Almería, Spain

Publication History

  1. Published Online: 27 JUN 2014
  2. Published Print: 23 JUL 2014

ISBN Information

Print ISBN: 9783527335220

Online ISBN: 9783527682492

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Keywords:

  • β-Amino acid;
  • dihydrouracil;
  • dihydropyrimidinase;
  • N-carbamoyl-β-alanine amidohydrolase;
  • green chemistry;
  • cascade reaction

Summary

β-Amino acids have attracted increasing attention over recent years, as they play a key role in chemical biology, the synthesis of natural products, and the manufacture of drugs. Substituted β-amino acids can be denominated β2, β3, and β2,3 depending on the position of the side chain(s) (R) on the amino acid skeleton. Historically, the synthesis of β-amino acids has relied predominantly on chemical methods. Recently, environmentally friendly methods that do not require high catalyst loadings have led to the emergence of biocatalysis as a new strategy for β-amino acids production. Both chemical and biocatalytic strategies have allowed the production of β-amino acids, but the resolutions of β2-amino acids have not yet been studied to the same extent as their β3 and β2,3 counterparts. The final part of the reductive catabolism of pyrimidines, involved in the breakdown of the cyclic amide ring to the corresponding β-amino acid, is catalyzed by the enzymes dihydropyrimidinase (hydantoinase, E.C. 3.5.2.2) and N-carbamoyl-β-alanine amidohydrolase (NCβAA) (β-alanine synthase, ureidopropionase, E.C. 3.5.1.6). According to our understanding, there is a conceptual similarity between the ‘hydantoinase process’, an enzymatic cascade that allows successful industrial-scale production of optically pure α-amino acids from racemic mixtures of 5-monosubstituted hydantoins, and the way that β-amino acids are produced with two enzymes. This chapter describes the characterization of a dihydropyrimidinase from Sinorhizobium meliloti (SmelDhp) and provides an in-depth study of the prokaryotic NCβAA isolated from Agrobacterium tumefaciens (Atβcar) able to produce β2-amino acids. It goes on to explain how the combination of both enzymes converts dihydrouracil derivatives into β-amino acid by a chemoenzymatic cascade.