Redox-reversible artificial metalloenzymes

氧化还原可逆人工金属酶

• 批准号: EP/T007338/1
• 负责人: Anne-Kathrin Duhme-Klair
• 金额: $ 93.58万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FT007338%2F1
• 关键词: Redox; reversible; artificial; metalloenzymes

As natural biocatalysts, enzymes have evolved over billions or years to be highly efficient and selective. Their application in both bioconversions and chemical syntheses is attractive because of their sustainability and environmental compatibility. However, for many applications, suitable naturally occurring enzymes are not available. Tailor-made artificial metalloenzymes, on the other hand, can combine the selectivity and biocompatibility of proteins with the reactivity and the reaction scope of synthetic catalysts and thus have the potential to expand the range of applications in which biocatalysts can be used, for example by making new-to-nature transformations accessible. Artificial metalloenzymes have not yet progressed into general use, mainly because the proteins and the catalysts are challenging and expensive to produce and, when the artificial enzyme is no longer required or active, its valuable components cannot easily be recycled.Inspired by the way bacteria acquire essential iron, we have developed a new iron-based anchor unit that connects synthetic catalysts to proteins, creating artificial enzymes, but on chemical reduction of the iron centre, the anchor unit disconnects and triggers the disassembly of the artificial enzymes. Hence both the protein and the synthetic catalyst can be recovered and recycled.In this project, we will explore the wider scope of these recyclable artificial enzymes and immobilise the protein scaffolds on solid supports to enable their integration into flow systems. In this way, the removal and replacement of catalysts that have lost activity becomes possible. Subsequent replacements with different catalysts would be of particular interest since this would not only allow the protein to be recycled but also enabling an easy switch from one catalysed reaction to another. The application of this 'catch-and-release' approach to immobilised artificial metalloenzyme design will provide a flexible toolbox for their preparation that allows catalysts, protein scaffolds and solid supports to be mixed, matched and recycled, for us and others to use, adapt and explore further, both in batch processes and in continuous flow.

作为天然的生物催化剂，酶已经进化了数十亿年，变得高效和有选择性。由于其可持续性和环境兼容性，它们在生物转化和化学合成方面的应用具有吸引力。然而，对于许多应用，合适的天然存在的酶是不可用的。另一方面，量身定制的人工金属酶可以将蛋白质的选择性和生物相容性与合成催化剂的反应性和反应范围结合起来，从而有可能扩大生物催化剂的应用范围，例如使新的自然转化成为可能。人工金属酶尚未得到普遍应用，主要是因为蛋白质和催化剂的生产具有挑战性和昂贵，而且当人工酶不再需要或不再具有活性时，其有价值的成分不易回收。受细菌获取必需铁的方式的启发，我们开发了一种新的铁基锚定单元，将合成催化剂与蛋白质连接起来，产生人工酶，但在铁中心的化学还原过程中，锚定单元断开并触发人工酶的分解。因此，蛋白质和合成催化剂都可以回收再利用。在这个项目中，我们将探索这些可回收人工酶的更广泛范围，并将蛋白质支架固定在固体支架上，使其能够整合到流动系统中。通过这种方法，去除和替换失去活性的催化剂成为可能。随后用不同的催化剂替代将是特别有趣的，因为这不仅可以使蛋白质被循环利用，而且可以很容易地从一种催化反应切换到另一种催化反应。这种“捕获和释放”方法在固定化人工金属酶设计中的应用，将为它们的制备提供一个灵活的工具箱，允许催化剂、蛋白质支架和固体支架混合、匹配和回收，供我们和其他人在批处理和连续流中使用、适应和进一步探索。

项目成果

Artificial metalloenzymes: The powerful alliance between protein scaffolds and organometallic catalysts

• DOI: 10.1016/j.cogsc.2020.100420
• 发表时间: 2021-01-01
• 期刊: CURRENT OPINION IN GREEN AND SUSTAINABLE CHEMISTRY
• 影响因子: 9.3
• 作者: Large, Benjamin;Baranska, Natalia G.;Duhme-Klair, Anne-Kathrin
• 通讯作者: Duhme-Klair, Anne-Kathrin

Siderophore-Linked Ruthenium Catalysts for Targeted Allyl Ester Prodrug Activation within Bacterial Cells.

• DOI: 10.1002/chem.202202536
• 发表时间: 2023-02-07
• 期刊: CHEMISTRY-A EUROPEAN JOURNAL
• 影响因子: 4.3
• 作者: Southwell, James W.;Herman, Reyme;Raines, Daniel J.;Clarke, Justin E.;Boeswald, Isabelle;Dreher, Thorsten;Gutenthaler, Sophie M.;Schubert, Nicole;Seefeldt, Jana;Metzler-Nolte, Nils;Thomas, Gavin H.;Wilson, Keith S.;Duhme-Klair, Anne-Kathrin
• 通讯作者: Duhme-Klair, Anne-Kathrin

Electrochemical and Solution Structural Characterization of Fe(III) Azotochelin Complexes: Examining the Coordination Behavior of a Tetradentate Siderophore.

• DOI: 10.1021/acs.inorgchem.2c02777
• 发表时间: 2022-12-05
• 期刊: INORGANIC CHEMISTRY
• 影响因子: 4.6
• 作者: Baranska, Natalia G.;Parkin, Alison;Duhme-Klair, Anne -K.
• 通讯作者: Duhme-Klair, Anne -K.

Augmentation of growth media for extreme iron-limitation in Escherichia coli

增强大肠杆菌的生长培养基以实现极端铁限制

• DOI: 10.1099/acmi.0.000735.v1
• 发表时间: 2023
• 作者: Southwell J

Artificial imine reductases: developments and future directions.

• DOI: 10.1039/d0cb00113a
• 发表时间: 2020-12-01
• 期刊: RSC chemical biology
• 影响因子: 4.1
• 作者: Booth RL;Grogan G;Wilson KS;Duhme-Klair AK
• 通讯作者: Duhme-Klair AK