The production of chiral amines through asymmetric synthesis using amine transaminase (ATA) has the potential for high yields in an efficient single-step process. Integrating in situ membrane extraction with this biocatalytic chiral amine production process has been demonstrated to reach higher yields by shifting the equilibrium position through product recovery. To date, however, it is unclear whether the in situ product recovery strategy is economically viable. This study carried out a techno-economic assessment to understand the main drivers of the manufacturing costs and to set quantitative development targets. The chiral amine products under study are (R)-(+)- or (S)-(−)-α-methylbenzylamine (MBA) and sitagliptin. Their manufacturing costs were quantified and benchmarked to three alternative production pathways. The results yield an MBA manufacturing cost of €17.8/mol for the integrated process with membrane extraction, which is lower than the cost for the benchmark process using an ion-exchange resin (€23.4/mol). The sitagliptin manufacturing cost is estimated to be €30.9/mol, which is €1.6/mol and €4.6/mol less than the benchmark process with engineered transaminase and the rhodium-catalyzed process, respectively. On the basis of the outcomes of sensitivity analyses, development targets were set for the membrane flux and selectivity and the product concentration, which are the key parameters that influence the manufacturing cost related to the membrane.

中文翻译：

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结合原位膜萃取的生物催化手性胺生产工艺的技术经济评估

使用胺转氨酶 (ATA) 通过不对称合成生产手性胺具有在高效的单步工艺中获得高产率的潜力。已经证明，将原位膜萃取与这种生物催化手性胺生产工艺相结合，可以通过通过产品回收改变平衡位置来达到更高的产率。然而，迄今为止，尚不清楚原位产品回收策略在经济上是否可行。本研究进行了技术经济评估，以了解制造成本的主要驱动因素并设定量化发展目标。正在研究的手性胺产品是 ( R )-(+)- 或 ( S)-(-)-α-甲基苄胺 (MBA) 和西格列汀。他们的制造成本被量化并以三种替代生产途径为基准。结果表明，采用膜萃取的集成工艺的 MBA 制造成本为 17.8 欧元/摩尔，低于使用离子交换树脂的基准工艺的成本（23.4 欧元/摩尔）。西格列汀的制造成本估计为 30.9 欧元/摩尔，分别比工程转氨酶和铑催化工艺的基准工艺低 1.6 欧元/摩尔和 4.6 欧元/摩尔。在敏感性分析结果的基础上，确定了膜通量和选择性以及产品浓度的开发目标，这些都是影响膜相关制造成本的关键参数。