Integration of simulated moving bed chromatography and enzymatic racemization for the production of single enantiomers

Integration of enantioseparation by simulated moving bed (SMB) and mild enzymatic racemization enables the production of single enantiomers from a racemic mixture in theoretically 100% yield and hence overcomes the 50% yield limitation of conventional SMB processes. We implemented such a process consisting of a Chirobiotic TAG column-SMB, an amino acid racemase-containing enzyme membrane reactor, and a nanofiltration unit for concentration of the distomer-enriched SMB raffinate prior to racemization on lab-scale for the production of enantiopure D-methionine. The integrated process scheme was operated continuously for over 30 h without significant variations in product concentration and purity and with a yield of 93.5%, demonstrating the feasibility of this integrated process concept. Furthermore, a rational analysis of the integrated process on the basis of a short-cut model was conducted. The process model consists of a true moving bed equilibrium stage model to represent the SMB, a continuous stirred tank reactor model with reversible Michaelis–Menten kinetics to represent the enzyme membrane reactor, a nanofiltration model and feed node mass balances, and enabled the identification of optimal operating points (flow rate ratios, enzyme concentration) at a variety of process specifications and objectives. Optimal operating points were calculated for different cost distributions between the applied materials such as stationary phase, enzyme, solvent, and nanofiltration membrane. By assigning plausible pricing data and lifetimes to the respective materials, variable costs for the specific process considered in this work were estimated.