Tufvesson Pär, Bach Christian, Woodley John M
Center for Process Engineering and Technology, Department of Chemical and Biochemical Engineering, Technical University of Denmark, Søltofts Plads, Building 229, Lyngby, 2800, Kgs, Denmark.
Biotechnol Bioeng. 2014 Feb;111(2):309-19. doi: 10.1002/bit.25017. Epub 2013 Aug 26.
Acetone removal by evaporation has been proposed as a simple and cheap way to shift the equilibrium in the biocatalytic asymmetric synthesis of optically pure chiral amines, when 2-propylamine is used as the amine donor. However, dependent on the system properties, this may or may not be a suitable strategy. To avoid excessive laboratory work a model was used to assess the process feasibility. The results from the current study show that a simple model of the acetone removal dependence on temperature and sparging gas flowrate can be developed and fits the experimental data well. The model for acetone removal was then coupled to a simple model for biocatalyst kinetics and also for loss of substrate ketone by evaporation. The three models were used to simulate the effects of varying the critical process parameters and reaction equilibrium constants (K eq) as well as different substrate ketone volatilities (Henry's constant). The simulations were used to estimate the substrate losses and also the maximum yield that could be expected. The approach was seen to give a clear indication for which target amines the acetone evaporation strategy would be feasible and for which amines it would not. The study also shows the value of a modeling approach in conceptual process design prior to entering a biocatalyst screening or engineering program to assess the feasibility of a particular process strategy for a given target product.
当使用2-丙胺作为胺供体时，通过蒸发去除丙酮被认为是一种简单且廉价的方法，可用于在生物催化不对称合成光学纯手性胺中移动平衡。然而，根据系统特性，这可能是也可能不是一种合适的策略。为避免过多的实验室工作，使用了一个模型来评估该过程的可行性。当前研究结果表明，可以开发一个关于丙酮去除率与温度和鼓泡气体流速关系的简单模型，该模型与实验数据拟合良好。然后将丙酮去除模型与生物催化剂动力学的简单模型以及底物酮蒸发损失的模型相结合。这三个模型用于模拟改变关键工艺参数和反应平衡常数（Keq）以及不同底物酮挥发性（亨利常数）的影响。这些模拟用于估计底物损失以及预期的最大产率。该方法能够明确指出丙酮蒸发策略对哪些目标胺可行，对哪些胺不可行。该研究还展示了在进入生物催化剂筛选或工程计划之前，在概念性工艺设计中使用建模方法来评估特定工艺策略对给定目标产品的可行性的价值。
