Transaminases for the synthesis of enantiopure beta-amino acids

Abstract

Optically pure β-amino acids constitute interesting building blocks for peptidomimetics and a great variety of pharmaceutically important compounds. Their efficient synthesis still poses a major challenge. Transaminases (also known as aminotransferases) possess a great potential for the synthesis of optically pure β-amino acids. These pyridoxal 5'-dependent enzymes catalyze the transfer of an amino group from a donor substrate to an acceptor, thus enabling the synthesis of a wide variety of chiral amines and amino acids. Transaminases can be applied either for the kinetic resolution of racemic compounds or the asymmetric synthesis starting from a prochiral substrate. This review gives an overview over microbial transaminases with activity towards β-amino acids and their substrate spectra. It also outlines current strategies for the screening of new biocatalysts. Particular emphasis is placed on activity assays which are applicable to high-throughput screening.

The specificity and kinetic mechanism of branched‐chain amino acid aminotransferase from Escherichia coli studied with a new improved coupled assay procedure and the enzyme's potential for biocatalysis

“…Apart from their evident metabolic importance, aminotransferases have biotechnological potential in view of their ability to handle a considerable range of substrates. In practice, they have been increasingly applied to large-scale synthesis of non-natural amino acids, which can be used as the building blocks for peptidomimetic and other single-enantiomer drugs in the pharmaceutical industry [1][2][3][4]. The most widely investigated are the a-transaminases, e.g.…”

Biochemical Properties and Crystal Structure of a β-Phenylalanine Aminotransferase from Variovorax paradoxus

“…The catalytic activities can be quite high (apparent k cat values up to 50 s Ϫ1 ) (35), and apart from PLP, which is sometimes added, there is no requirement for an external cofactor. Aminotransferases that catalyze synthesis or conversion of ␤-amino acids could be attractive for biocatalysis if they are enantioselective (36) and stable and exhibit a wide substrate scope. Here, we describe the gene cloning, the biochemical properties, and the three-dimensional (3D) structure of VpAT, an aromatic ␤-amino acid aminotransferase discovered in a strain of Variovorax paradoxus isolated from soil.…”

Transaminases and their Applications

“…Furthermore, unusual amino acids, for example, β-amino acids, deployed in peptidomimetics, offer higher stability against proteases. For the synthesis of unnatural amino acids or bulky amines, novel ω-transaminases are used [3][4][5][6][7]. Several synthesis strategies were established and optimized for transaminases, facing the challenges of product and substrate inhibition and the need to shift the equilibrium toward the product.…”