Synthesis of enantiopure 1,3/1,4- aminoalcohols from prochiral ketoacids

Fellow: ESR5
Host Institution: Junior Professorship Microbial Biotechnology, Ruhr University Bochum
Supervisors: R. Kourist (Ruhr University Bochum), B. Walse, D. Logan (Saromics), F. Moris, J. Sabin (Entrechem)

This PhD will focus on the development of novel enzyme cascades for the synthesis of enantiopure hydroxy amino acids and amino alcohols, valuable building blocks for the pharmaceutical industry. Objective is the widening of the substrate scope of an enzyme by protein engineering and directed evolution, and its application in organic synthesis. The highly interdisciplinary project encompasses methods from protein engineering and organic synthesis. It includes a secondment to Oviedo (Spain).

1. Generation of a broad-spectrum aminoacid decarboxylase by protein engineering
2. Application of broad-spectrum AAD for production of biogenic amines from aminoacids
3. Assembly of a new three-enzyme cascade with in situ cofactor (alpha-ketoglutarate) generation
4. Implementation of process at industrial partner and synthesis of 3-hydroxy-3-methylbutan-1-ol (non-chiral building block for cannaboid receptor antagonist) and (R)-4-amino-2- methylbutan-1-ol in 50 g-scale
5. Cost-benefit analysis

The Biocascades Project is a joint collaboration among the following university and industrial partners