Application of novel High Molecular Weight amine donors in chiral amine synthesis facilitates integrated downstream processing and provides in situ product recovery opportunities

摘要

The immense potential of transaminase-catalyzed reactions for chiral amine synthesis is often hampered by unfavorable thermodynamic equilibrium positions and product inhibition issues. In the here presented proof of concept, we demonstrate a membrane assisted strategy for addressing these challenges. It involves a separation based on differently sized amine donor and amine product molecules. Novel High Molecular Weight (HMW) amine donors, provided in excess for thermodynamic equilibrium shifting, are successfully employed in transaminase-catalyzed reactions and are effectively retained by commercial nanofiltration membranes by a size exclusion mechanism. Retention of HMW amine donors combined with selective product removal, in batch mode, shifted the equilibrium enhancing substrate conversion by an additional 25% compared to the control reaction. Along with the potential of this approach, certain limitations were also revealed in this study. Only few of the investigated enzymes accepted the HMW donor molecules, and along with very efficient amine product removal, there was undesirable loss of ketone substrate. Therefore, a broader enzyme screening, and the selection of a selective and solvent stable membrane, is essential for better and broader applicability of the concept.