Recent achievements in developing the biocatalytic toolbox for chiral amine synthesis

Novel enzyme activities and chemoenzymatic reaction concepts have considerably expanded the biocatalytic toolbox for chiral amine synthesis. Creating new activities or extending the scope of existing enzymes by protein engineering is a common trend in biocatalysis and in chiral amine synthesis specifically. For instance, an amine dehydrogenase that allows for the direct asymmetric amination of ketones with ammonia was created by mutagenesis of an L-amino acid dehydrogenase. Another trend in chiral amine chemistry is the development of strategies allowing for the synthesis of secondary amines. For example the smart choice of substrates for amine transaminases provided access to secondary amines by chemoenzymatic reactions. Furthermore novel biocatalysts for the synthesis of secondary amines such as imine reductases and Pictet-Spenglerases have been identified and applied. Recent examples showed that the biocatalytic amine synthesis is emerging from simple model reactions towards industrial scale preparation of pharmaceutical relevant substances, for instance, as shown in the synthesis of a Janus kinase 2 inhibitor using an amine transaminase. A comparison of important process parameters such as turnover number and space-time yield demonstrates that biocatalytic strategies for asymmetric reductive amination are maturing and can already compete with established chemical methods.