(26d) Scalable Continuous Synthesis of Enantiomerically Pure Amine APIs in an Enzyme Membrane Reactor
- Conference: AIChE Annual Meeting
- Year: 2017
- Proceeding: 2017 Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Sunday, October 29, 2017 - 4:45pm-5:10pm
We present the first example of a continuous process for chiral amine synthesis with AmDHs, employing an enzyme membrane reactor (EMR). The EMR consists of a continuously stirred reaction volume with a semipermeable UF membrane at the outlet which traps macromolecules within the reactor, but allows the small molecule substrates and products to pass2-3. Conversion of substrates is measured by following the change in the optical rotation of the outlet stream with a polarimeter. This rapid, online measurement allows for constant control of conversion, which is crucial for process optimization.
In this presentation, we outline the initial process development for this new reactor system for the synthesis of a model chiral amine compound. This begins with the characterization of the kinetic parameters of both enzymes which will determine rates and inhibition patterns. After a stable operating point is determined, the space-time yield (STY) can be determined. As we examine the enzyme deactivation behavior over a period of multiple days, the total turnover number (TTN) for both enzymes is obtained and will be reported. Data from these experiments will be used to optimize STY and TTN. Lastly, we will analyze continuous amine production via EMR with Green Chemistry metrics.
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3. Kragl, U.; Kruse, W.; Hummel, W.; Wandrey, C., Enzyme engineering aspects of biocatalysis: Cofactor regeneration as example. Biotechnology and Bioengineering 1996, 52 (2), 309-319.