I-Corps: An efficient enzymatic synthesis method for biomanufacturing of nucleoside analogues

核苷模拟物及其缀合物（称为核苷类似物或“NAs”）具有多种应用，从抗病毒和抗肿瘤剂到营养补充剂。目前合成NAs的化学方法耗时、昂贵且效率低下。最近，研究人员开发了一种酶辅助生物化学合成NAs的高产、一锅、一步反应。I-Corps提案的目标是将其发展成一个强大的生物制造过程，并探索可以使用这种酶方法合成的NAs的化学多样性。研究人员将酶促水基NAs合成技术设想为制造廉价、快速、高效和立体选择性的NAs的核心技术。这一过程也将是一种环境友好的替代方法，以取代目前可用的产生大量化学废物的化学方法。目前制备NAs的化学合成方法多步骤、耗时且产生大量化学废物。这限制了NAs作为潜在治疗剂、诊断工具、生化探针和营养补充剂的研究和开发范围。在水基中使用酶促反应不会产生废物，从而有利于环境。该方法可用于高通量筛选可与NAs偶联的小分子的化学空间，极大地增强了对高效NAs的搜索。NAs用于治疗艾滋病毒和丙型肝炎病毒等全球流行病。以更便宜的价格生产抗病毒药物以满足第三世界国家的需求尚未得到满足。通过使用具有成本效益的酶促合成NAs，人们可以想象以可承受的价格大规模生产这些药物。

Nucleoside mimics and their conjugates (referred to as nucleoside analogues or "NAs") have diverse applications ranging from anti-viral and anti-tumor agents to nutritional supplements. Current chemical approaches for the synthesis of NAs are time consuming, expensive, and inefficient. Recently, researchers developed an enzyme-assisted biochemical synthesis of NAs in high yield and in a one-pot, single step reaction. The goals of the I-Corps proposal are to develop this into a robust biomanufacturing process and explore the chemical diversity of NAs that can be synthesized using this enzymatic approach. Researchers envision the enzymatic aqueous-based synthesis of NAs as the core technology for the manufacture of NAs that is inexpensive, rapid, highly efficient, and stereo selective. The process would also be an environmentally-friendly alternative to the currently available chemical approaches which generate large quantities of chemical waste.Current chemical synthesis methods to make NAs are multi step, time consuming and generate significant chemical waste. This limits the scope of research and development of NAs as potential therapeutic agents, diagnostic tools, biochemical probes, and nutritional supplements. Using enzymatic reaction in aqueous base will produce no waste and thus help the environment. The adoptability of the proposed method for high-throughput screening of the chemical space of the small molecules that can be conjugated to the NAs greatly enhances the search for highly effective NAs. NAs are used in the treatment of global epidemics such as HIV and HCV. There is an unmet need to produce anti-viral drugs at a cheaper price to cater to the third world countries. By using cost effective enzymatic synthesis of NAs, one can imagine mass production of these drugs at affordable prices.