The enzymatic transamination of ketones into (R)-amines represents an important route for accessing a range of pharmaceuticals or building blocks. Although many publications have dealt with enzyme discovery, protein engineering, and the application of (R)-selective amine transaminases [(R)-ATA] in biocatalysis, little is known about the actual in vivo role and how these enzymes have evolved from the ubiquitous a-amino acid transaminases (alpha-AATs). Here, we show the successful introduction of an (R)-transaminase activity in an alpha-amino acid aminotransferase with one to six amino acid substitutions in the enzyme's active site. Bioinformatic analysis combined with computational redesign of the D-amino acid aminotransferase (DATA) led to the identification of a sextuple variant having a specific activity of 326 milliunits mg(-1) in the conversion of (R)-phenylethylamine and pyruvate to acetophenone and b-alanine. This value is similar to those of natural (R)-ATAs, which typically are in the range of 250 milliunits mg(-1). These results demonstrate that (R)-ATAs can evolve from alpha-AAT as shown here for the DATA scaffold.