Combining amine transaminase (ATA) and keto reductase (KRED) for 1-amino-cyclohexane-4-ol synthesis.

Fellow: ESR7
Host Institutions: Junior Professorship for Protein Biochemistry, Ernst Moritz Arndt University Greifswald
Supervisors: M. Höhne (University Greifswald), F. Moris, J. Sabin (Entrechem), R. Wardenga (Enzymicals)

The research project “Combining amine transaminase (ATA) and keto reductase (KRED) for 1-amino-cyclohexane-4-ol synthesis” presupposes obtaining of optically pure 1-amino-cyclohexane-4-ol, applying enzymatic transamination and ketoreduction.1-amino-cyclohexane-4-ol is a valuable building block for active pharmaceutical ingredients such as lombuvir (HCV protease inhibitor)and ambroxol (a secretolytic agent). As 1-amino-cyclohexane-4-ol can exist only as trans- or cis-isomer, it is a quite suitable commercial target and will be used as a model substratefor the validation of an enzymatic 1,4-amino alcohol synthesis by the combination of two above mentioned enzymes.

Objectives
1. Establishment of analytical procedures for substrates and products, identification of enantio- and regioselective ATA and KRED for synthesis of 1,4-amino alcohols, and optimization of the reaction cascade
2. Proof of concept of the amine transaminase / ketoreductase cascade and implementation of efficient equilibrium shift.
3. Analysis of bottlenecks of the cascade and optimization of the process and upscaling for industrial production

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