Biocatalytic Membrane Reactors for Sustainable Fine Chemical Production

精细化学品的产量有限，价格相对较高，估计全球每年的产值约为850亿美元。利用膜对试剂、产物和催化剂进行纯化、分离和循环利用，在高价值精细化学品如生物药品的可持续合成中得到越来越多的关注。在过去的几十年里，已经开发了大量的材料和工艺来协同结合膜和有机介质中的催化作用，涵盖了从微流体到酶的各个学科。酶是一种能加快化学反应速度的蛋白质。它们具有区域选择性、对映性和立体选择性，可以进行高原子效率的反应，在比传统有机转化更低的操作温度下工作，并且产生更少的溶剂浪费。因此，它们正被纳入生产高价值化学品的工业过程中。几乎所有这些酶促反应都是分批进行的，而不是连续进行的。这将导致耗时的分离和恢复步骤。此外，许多酶转化产物被抑制，导致在加工过程中收益递减。纳米孔膜具有小分子大小的孔。这些孔允许连续净化产物和同时定量回收有价值的生物催化剂，而不需要停止反应和重新激活催化系统。产品回收率可以与反应物添加率相平衡，以最大限度地提高工艺效率并最大限度地减少产品抑制。该项目将从蛋白质处理、生化分析、膜生产、液相分离和表征方法（如液相色谱和电子显微镜）的培训开始。学生将首先从商业上获得酶，并在非水条件下筛选它们的催化活性。由于药物底物的高溶解度，提高了某些生物催化剂的稳定性和动力学性能，因此选择有机溶剂作为反应介质。最初的研究将集中在同质系统上。长期目标是创建一个混合系统，其中酶被固定在纳滤膜的表面，以创建一个“一体化”组件，用于连续的化学处理。所产生的酶膜反应器的可行性将通过一个药物案例研究进行评估。将进行绿色指标和技术经济分析，以评估混合系统的整体可持续性。

Fine chemicals are produced in limited volumes at relatively high prices with an estimated global production value of about $85 billion annually. The application of membranes to purify, isolate and recycle the reagents, products and catalysts has gained increasing attention for the sustainable synthesis of high-value fine chemicals such as (bio)pharmaceuticals. In the last decades, a plethora of materials and processes have been developed to synergistically combine membranes and catalysis in organic media, covering various disciplines from microfluidics to enzymes. Enzymes are proteins that increase the rate of chemical reactions. They are regio-, enantio- and stereoselective, can carry out reactions with a high atom efficiency, work at lower operating temperatures than conventional organic transformations, and create less solvent waste. Therefore, they are being integrated into industrial processes for the production of high-value chemicals. Almost all of these enzymatic reactions are carried out in batch rather than continuous processes. This leads to time-consuming separation and recovery steps. Also, many enzymatic transformations are product inhibited, leading to diminishing returns during processing. Nanoporous membranes have pores the size of small molecules. These pores allow for the continuous purging of the product and simultaneous quantitative recovery of the valuable biocatalyst without the need to stop the reaction and reactivate the catalytic system. The rate of product recovery can be balanced with the rate of reactant addition to maximise the efficiency of the process and minimise product inhibition. The project will begin with training in protein handling, biochemical assays, membrane production, liquid-phase separations, and characterisation methods such as liquid chromatography and electron microscopy. The student will initially source enzyme commercially and screen them for catalytic activity under non-aqueous conditions. Organic solvents have been selected as reaction media due to the high solubility of the pharmaceutical substrates, increased stability and kinetic performance of certain biocatalysts. Initial studies will focus on homogeneous systems. A longer-term objective is to create a hybrid system in which the enzymes are immobilised on the surface of the nanofiltration membrane to create an 'all-in-one' component for continuous chemical processing. The viability of the resulting enzymatic membrane reactor will be evaluated through a pharmaceutical case study. Green metrics and techno-economic analysis will be performed to assess the overall sustainability of the hybrid system.