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)-(−)-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.

Acrylic Acid Removal Using Membrane Contactors during Acrylate Downstream Processing: A Techno-economic Assessment

“…The TEA is performed following four steps: (1) market study, (2) process flow diagram and mass and energy balance, (3) economic analysis, and (4) sensitivity analysis, in line with previous studies. − In step 1, we gather information about the price of the target product 2-EHA and its determinants, such as its manufacturing process and scale. In step 2, the manufacturing processes are designed for both the membrane-assisted process and the water washing process.…”

“…The economic assessment of membrane technologies has been conducted for various applications, especially water treatment, as reviewed by Judd and by Okamoto and Lienhard . The membrane cost, lifetime, and mass transfer rate were found to be decisive for their economic feasibility. − No study has yet assessed the drivers of economic feasibility for membrane-assisted AA removal.…”

Two anti‐Prelog NAD‐Dependent Alcohol Dehydrogenases with Broad Substrate Scope and Excellent Enantioselectivity

“…This common NADP(H)‐dependence for anti‐Prelog ADHs results in a less attractive applicability because of the ca. four‐times higher cost of NADP + compared with NAD + [13] . However, anti‐Prelog ADHs are important as they can give access to the complementary alcohol enantiomer (e. g., like the ( R )‐configured one in the case of the reduction of acetophenone as model substrate) [10e,14] .…”

“…four-times higher cost of NADP + compared with NAD + . [13] However, anti-Prelog ADHs are important as they can give access to the complementary alcohol enantiomer (e. g., like the (R)-configured one in the case of the reduction of acetophenone as model substrate). [10e,14] For this reason, anti-Prelog ADHs have been engineered in the past to switch the co-enzyme acceptance from NADPH to NADH such as in the case of the ADH from Lactobacillus brevis or other dehydrogenases.…”