A Techno-economic Assessment of a Biocatalytic Chiral Amine Production Process Integrated with In Situ Membrane Extraction

Abstract

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)-(-)-alpha-methylbenzylamine (MBA) and sitagliptin. Their manufacturing costs were quantified and benchmarked to three alternative production pathways. The results yield an MBA manufacturing cost of (sic)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 ((sic)23.4/mol). The sitagliptin manufacturing cost is estimated to be (sic)30.9/mol, which is (sic)1.6/mol and (sic)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.