CCI Phase I: NSF Center for Chemoenzymatic Synthesis

化学酶合成中心(C-CES)由化学部化学创新中心(CCI)项目支持。酶是控制和催化生命所必需的化学反应的蛋白质。几十年来，自然界利用这些高度进化的生物催化剂通过选择性反应产生各种复杂分子的能力启发了化学家，并导致了生物催化领域的发展。生物催化的潜在社会影响是显著的，然而化学家直到最近才开始利用这些有效和选择性的自然过程。C-CES试图通过将生物催化中的新概念应用于化学物质的可持续制造，即化学酶合成，来开发前所未有的转化和实现新的选择性策略。这些进展将使科学界能够应对21世纪在新药和材料生产方面的挑战。该中心的更广泛影响将集中在对早期职业科学家进行趋同、跨学科的化学酶合成、团队建设和交流方面的教育，所有这些都将为他们的独立职业生涯奠定基础。该中心将站在开发和传播资源的前列，将生物催化纳入大学和工业环境以及化学课程和实验室的广泛实践中。最后，该中心将为每个团队成员建立现有的机构资源，以从代表性不足的群体中招募、聘用和教育个人，从而扩大化学酶合成的影响。C-CES将通过在生物催化和化学酶合成方面的新发现，推动有机合成领域的一个未知前沿。该中心将专注于通过将生物催化和生物启发的转化与现有的化学合成方法相结合，以可持续的方式为碳-碳和碳-杂原子键的形成创造新的选择性反应这一重大挑战。中心活动将结合小分子催化的基本概念和过去的成功，以及通过超分子蛋白质催化剂获得的效率和选择性控制的独特优势。该中心将汇集在催化、有机合成、化学酶合成、机器学习、高通量实验、蛋白质工程和生物催化等领域具有互补专业知识的国际公认的科学家。该中心的两个初始目标是生物催化形成高价值的C-C和C-X键，以及控制目前通过常规策略无法获得的选择性结果。这些努力的实现将受到实验研究和学生培训的协作和融合方法的推动，这种方法将反应开发和生物催化剂设计的最先进战略与机器学习和逆向合成规划相结合。该中心将监督协调的培训活动，以确保C-CES参与者获得掌握并随后在合成中使用生物催化所需的各种知识和技术。该奖项的主要广泛影响包括：a)开发生物催化研讨会，以培训未来的科学家关于实用策略和化学酶合成方法；b)为更广泛的化学界开发围绕生物催化概念的课程；以及c)公众参与化学酶合成的可持续应用，以获取影响我们日常生活的创新材料。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The Center for ChemoEnzymatic Synthesis (C-CES) is supported by the Centers for Chemical Innovation (CCI) Program in the Division of Chemistry. Enzymes are proteins that control and catalyze chemical reactions essential for life. Nature’s ability to employ these highly evolved biological catalysts to generate diverse and complex molecules through selective reactions has inspired chemists for decades and has led to the field of biocatalysis. The potential societal impacts of biocatalysis are significant, yet chemists have only recently begun to leverage these efficient and selective natural processes. C-CES seeks to develop unprecedented transformations and achieve new selectivity strategies by applying novel concepts in biocatalysis to sustainable making of chemicals, which are referred to as chemoenzymatic synthesis. These advances will allow the scientific community to address 21st-century challenges in the production of new medicines and materials. The broader impacts of the Center will focus on convergent, interdisciplinary education of early career scientists in chemoenzymatic synthesis, team building, and communication, all which will build the foundation for their independent careers. The Center will be at the forefront of developing and disseminating resources to integrate biocatalysis into broad practice across university and industrial settings, as well as in chemistry courses and laboratories. Finally, the Center will build up existing institutional resources of each team member to recruit, engage, and educate individuals from underrepresented groups, thereby broadening the impact of chemoenzymatic synthesis. C-CES will drive an unexplored frontier of organic synthesis by enabling new discoveries in biocatalysis and chemoenzymatic synthesis. The Center will focus on the grand challenge of creating new selective reactions for carbon-carbon and carbon-heteroatom bond formation in a sustainable manner by combining biocatalytic and bioinspired transformations with established chemical synthesis methodologies. Center activities will integrate fundamental concepts and past success of small molecule catalysis with the unique advantages of efficiency and selectivity control available through supramolecular protein-based catalysts. The Center will bring together internationally recognized scientists with complementary areas of expertise in catalysis, organic synthesis, chemoenzymatic synthesis, machine learning, high-throughput experimentation, protein engineering and biocatalysis. The two initial goals of the Center are the biocatalytic formation of high value C–C and C–X bonds and controlling selectivity outcomes currently unobtainable through conventional strategies. The realization of these efforts will be driven by a collaborative and convergent approach to experimental research and student training that combines state-of-the-art strategies for reaction development and biocatalyst design with machine learning and retrosynthesis planning. The Center will oversee coordinated training activities to ensure C-CES participants acquire diverse knowledge and techniques needed to master and then utilize biocatalysis in synthesis. The main broader impacts of this award include: a) the development of biocatalysis workshops to train future scientists on practical strategies and approach to chemoenzymatic synthesis; b) curriculum development around biocatalysis concepts for the broader chemical community; and c) public engagement regarding the sustainable applications of chemoenzymatic synthesis to access innovative materials that impact our everyday lives.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.