Understanding and Controlling the Selectivity of Visible Light Photocatalysis in Metal Polypyridyl Artificial Metalloenzymes

了解和控制金属聚吡啶人工金属酶中可见光光催化的选择性

• 批准号: 2154726
• 负责人: Jared Lewis
• 金额: $ 49.68万
• 依托单位: Indiana University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154726&HistoricalAwards=false
• 关键词: Understanding; Controlling; Selectivity; Visible; Light

With the support of the Chemical Catalysis Program in the Division of Chemistry, Jared C. Lewis of Indiana University is studying a new class of artificial metalloenzymes (ArMs) that promise to advance the field of photocatalysis by offering significant improvements in selectivity and function over existing technologies. The proposed ArMs incorporate synthetic catalysts that use visible light to effect a broad range of challenging chemical reactions, into protein scaffolds that will enable spatial control over the course of these reactions. As such, the designed ArM constructs will provide a unique platform to control the selectivity of reactions that are useful for chemical synthesis and potentially applicable for the manufacture of pharmaceuticals, agrochemicals, and other advanced materials. The broader impacts of the funded project will extend to an integrated outreach program focused on improving understanding of the important topic of biocatalysis among graduate, undergraduate, and high school students via innovative educational content modules. To complement this activity, a high school teacher professional development program will be developed that likewise explores the theme of biocatalysis.Understanding how enzymes can serve as hosts for different catalytic reactions and how second sphere interactions and conformational dynamics influence the properties and reactivity of metal cofactors, would greatly improve our ability to use proteins as supramolecular hosts for catalysis. Furthermore, the insights gained from such endeavors will shed light on design principles for implementing second sphere interactions more broadly in catalysis. Previous studies in the Lewis group led to the development of ArMs based on a prolyl oligopeptidase (POP) scaffold and robust methods to evolve these ArMs were identified. The work revealed that attractive interactions and conformational dynamics impact cofactor binding/bioconjugation, catalytic selectivity, and photophysical properties of metal complexes linked to POP. The funded project takes these ideas further and it will focus on the development of a new class of POP-based metal polypyridine ArMs while entailing efforts to: (a) understand metal polypyridine binding and photophysical properties within POP, (b) evolve covalent metal polypyridine ArMs for selective photoredox and energy transfer catalysis, and (c) engineer non-covalent ArMs to control the selectivity of commercially available photocatalysts. The planned research aims to illuminate on how non-covalent interactions in a conformationally dynamic protein scaffold can modulate cofactor reactivity. This approach will complement efforts in bioinorganic chemistry to model metallocofactors with static synthetic cofactor analogues or the effects of static protein scaffolds on metal ion reactivity. The potential to control the selectivity of a broad range of photoredox properties using the proposed ArMs also has the potential to significantly impact synthetic methodology. These studies will provide an ideal backdrop for improving understanding of biocatalysis at multiple levels.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.

在化学系化学催化项目的支持下，印第安纳大学的 Jared C. Lewis 正在研究一类新型人造金属酶 (ArM)，该酶有望通过在选择性和功能方面比现有技术显着改进来推动光催化领域的发展。技术。拟议的 ArM 将合成催化剂纳入蛋白质支架中，利用可见光来实现各种具有挑战性的化学反应，从而实现对这些反应过程的空间控制。因此，设计的 ArM 结构将提供一个独特的平台来控制反应的选择性，这对化学合成有用，并可能适用于药物、农用化学品和其他先进材料的制造。该资助项目的更广泛影响将延伸到一个综合外展计划，重点是通过创新的教育内容模块提高研究生、本科生和高中生对生物催化这一重要主题的理解。为了补充这一活动，将开发一个高中教师专业发展计划，同样探索生物催化的主题。了解酶如何作为不同催化反应的宿主，以及第二球体相互作用和构象动力学如何影响金属辅因子的性质和反应性，将大大提高我们使用蛋白质作为超分子宿主进行催化的能力。此外，从这些努力中获得的见解将揭示在催化中更广泛地实现第二领域相互作用的设计原则。 Lewis 小组之前的研究导致了基于脯氨酰寡肽酶 (POP) 支架的 ArM 的开发，并确定了进化这些 ArM 的稳健方法。该工作表明，吸引相互作用和构象动力学影响与 POP 相关的金属配合物的辅因子结合/生物共轭、催化选择性和光物理性质。该资助项目进一步发展了这些想法，重点是开发一类新型基于 POP 的金属聚吡啶 ArM，同时努力：(a) 了解 POP 中金属聚吡啶的结合和光物理性质，(b) 进化共价金属聚吡啶用于选择性光氧化还原和能量转移催化的 ArM，以及 (c) 设计非共价 ArM 以控制市售光催化剂的选择性。该计划的研究旨在阐明构象动态蛋白质支架中的非共价相互作用如何调节辅因子反应性。这种方法将补充生物无机化学领域的努力，用静态合成辅因子类似物模拟金属辅因子或静态蛋白质支架对金属离子反应性的影响。使用所提出的 ArM 控制各种光氧化还原特性的选择性的潜力也有可能对合成方法产生重大影响。这些研究将为提高对多个层面的生物催化的理解提供理想的背景。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Non-Native Anionic Ligand Binding and Reactivity in Engineered Variants of the Fe(II)- and α-Ketoglutarate-Dependent Oxygenase, SadA.

• DOI: 10.1021/acs.inorgchem.2c02872
• 发表时间: 2022-09-12
• 期刊: INORGANIC CHEMISTRY
• 影响因子: 4.6
• 作者: Chan, Natalie H.;Gomez, Christian A.;Vennelakanti, Vyshnavi;Du, Qian;Kulik, Heather J.;Lewis, Jared C.
• 通讯作者: Lewis, Jared C.

First and second sphere interactions accelerate non-native N-alkylation catalysis by the thermostable, methanol-tolerant B12-dependent enzyme MtaC.

第一球体和第二球体相互作用通过热稳定、耐甲醇的 B12 依赖性酶 MtaC 加速非天然 N-烷基化催化。

• DOI: 10.1039/d3cc01071f
• 发表时间: 2023
• 期刊: Chemical communications (Cambridge, England)
• 作者: Kumar,Amardeep;Yang,Xinhang;Li,Jianbin;Lewis,JaredC
• 通讯作者: Lewis,JaredC