Chiral drugs become a more and more important market for the Fine Chemical business. Diastereoisomeric crystallization of salts and kinetic resolution are common methods of separating enantiomers on commercial scale. However, these methods are limited to 50% yield of the desired enantiomer.
Beside asymmetric chemical methods the use of biocatalysts in the production of chiral compounds can lead to 100% chemical and optical yield.
A key factor for the successful development of biocatalytic processes is a fast access to cheap biocatalysts at large scale with suitable properties such as high activity, high stability and high selectivity. Unfortunately, industrial enzymes are often not available off-the-shelf for a desired reaction or show properties incompatible with industrial demands. However, the application of molecular biology techniques allows us to rapidly screen and design biocatalysts for new applications.
Here we provide examples for the development of processes for the production of optically pure amino acids by integration of biological tools such as design and screening of novel biocatalysts.
Two different dynamic kinetic resolution processes for the production of natural and non-natural L-amino acids have been established at Degussa. The first process is based on the resolution of 5’-monosubstituted hydantoins and the second based on the resolution of N-acetyl amino acids using an acylase in combination with a racemase. These platform technologies have been recently expanded by a process using oxido-reductases and a co-factor regeneration system for production of amino acids and chiral molecules starting from pro-chirale ketones.