Pushing Heterogeneous Catalysis into Biological Chemistry via Cofactor Regeneration

通过辅因子再生将多相催化推向生物化学

• 批准号: EP/V048635/1
• 负责人: Xiaodong Wang
• 金额: $ 25.78万
• 依托单位: Lancaster University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FV048635%2F1
• 关键词: Pushing; Heterogeneous; Catalysis; into; Biological

Heterogeneous catalysts are well regarded as the workhorses of chemical transformations, being involved in over 90% of all industrial processes. Although heterogeneous catalysis offers many advantages over traditional synthetic routes, there are still some major areas where it is still lacking. For instance, with albeit a history of around 200 years, the majority of industrial processes and research using heterogeneous catalysed systems have thus far focused on either relatively small molecules (e.g. ammonia synthesis, Fischer-Tropsch process, natural gas reforming and water gas shift reactions), or traditional petrochemical/biomass feedstock (e.g. hydrocracking, polymerisation and biomass gasification, pyrolysis) and has neglected large biological molecules (such as the enzymatic cofactors) as reactants or products (in this context, "heterogeneous" refers to conventional solid bulk phase or supported metal catalysts, not immobilised enzymes or mimics). To expand the boundaries of heterogeneous catalysis to biochemistry in areas traditionally seen as belonging to biological enzymes will be fundamentally interesting, novel and attractive, facilitating potentially new routes for clean pharmaceutical and chemical production.Cofactor NAD(P)H is a critical reducing agent participating in enzymatic reductions for the synthesis of pharmaceutical/chemical products. A notable example of these products is "atorvastatin" (the active ingredient) for Lipitor ($11.9 billion global sale in 2010) which can lower the risk for heart attack and stroke, etc. or risk factors for heart disease (age, smoking, high blood pressure, etc.). The high cost of NAD(P)H and stoichiometric use make its regeneration essential for practical applications. There have been five existing methods (enzymatic, chemical, homogeneous catalytic, photo- and electro- catalytic) for this regeneration. Astonishingly, at least in part because there has been little knowledge in introducing supported metal catalysts to biological chemistry, nobody has embarked on serious studies of the potential of heterogeneous catalysts in cofactor regeneration and associated applications. This is what we plan to do. A fundamental understanding of the mechanism in the heterogeneous catalytic regeneration pathway and optimal solid catalysts will be obtained. The ultimate goal is to develop an efficient and clean process for cofactor regeneration that can work with biotransformations, taking enzymatic synthesis of pharmaceutical intermediates and CO2 conversion as representative applications.

异质的催化剂被众所周知，是化学转化的工作主场，涉及所有工业过程的90％以上。尽管异质性催化与传统合成路线相比具有许多优势，但仍然缺乏一些主要领域。 For instance, with albeit a history of around 200 years, the majority of industrial processes and research using heterogeneous catalysed systems have thus far focused on either relatively small molecules (e.g. ammonia synthesis, Fischer-Tropsch process, natural gas reforming and water gas shift reactions), or traditional petrochemical/biomass feedstock (e.g. hydrocracking, polymerisation and biomass gasification,热解）并忽略了大型生物分子（例如酶促辅因子）作为反应物或产物（在这种情况下，“异质”是指常规的固体散装相或支持的金属催化剂，而不是固定化的酶或模拟物）。 To expand the boundaries of heterogeneous catalysis to biochemistry in areas traditionally seen as belonging to biological enzymes will be fundamentally interesting, novel and attractive, facilitating potentially new routes for clean pharmaceutical and chemical production.Cofactor NAD(P)H is a critical reducing agent participating in enzymatic reductions for the synthesis of pharmaceutical/chemical products.这些产品的一个值得注意的例子是Lipitor的“ Atorvastatin”（2010年全球销售）的“ Atorvastatin”（活跃成分），这可以降低心脏病发作和中风等的风险，或者是心脏病（年龄，吸烟，高血压等）的风险因素。 NAD（P）H和化学计量的高成本使其对实际应用必不可少。这种再生有五种现有方法（酶，化学，均匀催化，光催化和电催化）。令人惊讶的是，至少部分是因为在将支持的金属催化剂引入生物化学方面几乎没有知识，所以没有人开始认真研究异质催化剂在辅因子再生和相关应用中的潜力。这就是我们打算做的。将获得对异质催化再生途径和最佳固体催化剂的基本理解。最终目标是为辅因子再生开发一个有效，清洁的过程，该过程可以与生物转化一起使用，将药物中间体的酶促合成和CO2转换作为代表性应用。

项目成果

Supported Pt Enabled Proton-Driven NAD(P)+ Regeneration for Biocatalytic Oxidation.

• DOI: 10.1021/acsami.2c01743
• 发表时间: 2022-04
• 期刊: ACS applied materials & interfaces
• 影响因子: 9.5
• 作者: Joseph W. H. Burnett;Hui Chen;Jianwei Li;Ying Li;Shouying Huang;Jiafu Shi;A. Mccue;R. Howe;S. Minteer;Xiaodong Wang

Oxide-supported metal catalysts for anaerobic NAD+ regeneration with concurrent hydrogen production

• DOI: 10.1016/j.cclet.2023.108737
• 发表时间: 2023-06
• 期刊: Chinese Chemical Letters
• 影响因子: 9.1
• 作者: Jianwei Li;Joseph W. H. Burnett;C. M. Macias;R. Howe;Xiaodong Wang