276787 From Racemate to Single Enantiomer with 100% YIELD
Integration of SMB enantioseparation and mild enzymatic racemization allows for obtaining the target enantiomer from the racemic mixture in theoretically 100% yield- compared to 50% yield with a stand-alone chiral SMB .
Next, such a process gives access to both enantiomers with one SMB installation and one enzyme compared to the three enzymes required in dynamic kinetic resolution approaches for the same flexibility.
In this work we present the design and operation of an integrated process realized by coupling of an SMB equipped with Chirobiotic TAG (Sigma Aldrich, USA) columns , a nanofiltration concentration deviceand an enzyme membrane reactor containing an amino acid racemase for the production of enantiopure amino acids, specifically D-methionine (Fig.1).
However, due to the direct coupling the same solvent needs to be applied in all unit operations. Hence, the design and optimization of a fully integrated production system require a detailed characterization and accurate parameterization of all involved units with respect to potentially inter-operable solvent compositions, specifically reaction kinetics and stability, adsorption isotherms and rejection of the nanofiltration membrane. Based on these parameters model-based design is applied in order to identify appropriate operating points for aset of specifications such as product purity. The usefulness of the obtained design is evaluated by experimental runs of the fully integrated process. This constitutes the first report on the experimental implementation of integration of chiral SMB and enzymatic racemization.
1) M. Bechtold, S. Makart, M. Heinemann, S. Panke, Journal of Biotechnology 124 (2006) 146
2) M.Fuereder, S.Panke, M.Bechtold, Journal of Chromatography 1236 (2012), 123