Transaminases for the synthesis of enantiopure beta-amino acids

Since the discovery of transamination in biological systems (Braunstein and Kritzmann 1937Moyle Needham 1930) the significance of transaminases (TAs) for amino acid metabolism has been the subject of intensive research. Over the last 15 years, TAs have gained increasing attention in organic synthesis for the biocatalytic production of a wide variety of chiral amines and α-amino acids. This has been discussed in detail in a series of excellent reviews (H？hne and Bornscheuer 2009; Koszelewski et al. 2010; Taylor et al. 1998; Ward and Wohlgemuth 2010). Advantages in the use of TAs lie in mostly low-cost substrates, no necessity for external cofactor recycling and the enzymes' high enantioselectivity and reaction rate. For the synthesis of enantiopure β-amino acids only a limited number of TAs are available. Therefore efficient screening techniques for TAs with high activities as well as broader substrate specificity and different enantioselectivities are crucial for the successful application of transaminases for the synthesis of β-amino acids. Of particular interest are methods that can be used at small scale compatible with microtiter plates.Enantiopure β-amino acids represent highly valuable building blocks for peptidomimetics and the synthesis of bioactive compounds. In order to distinguish positional isomers of β-amino acids, the terms β2-, β3- and β2,3-amino acids have been introduced by Seebach and coworkers (Hintermann and Seebach 1997; Seebach et al. 1997). With the exception of β-alanine and β-aminoisobutyric acid which constitute key intermediates in several metabolic pathways, β-amino acids are not as abundant in nature as α-amino acids. However, they occur as essential parts in a variety of biologically active compounds. Notable representatives are the antineoplastic agent paclitaxel (= Taxol？, Bristol-Myers Squibb) (Wani et al. 1971) and the chromophore of C-1027 (= lidamycin), a radiomimetic antitumor agent (Hu et al. 1988) (Figure 1a). β-Amino acids hav