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.

多相催化剂被认为是化学转化的主力，参与了 90% 以上的工业过程。尽管多相催化比传统合成路线具有许多优势，但仍存在一些主要领域的不足。例如，尽管已有约 200 年的历史，但迄今为止，使用多相催化系统的大多数工业过程和研究都集中在相对较小的分子（例如氨合成、费托工艺、天然气重整和水煤气变换反应） ），或传统的石化/生物质原料（例如加氢裂化、聚合和生物质气化、热解），并且忽略了大生物分子（例如酶促辅因子）作为反应物或产物（在本文中，“异质”是指常规固体本体相或负载金属催化剂，而不是固定化酶或模拟物）。在传统上被视为属于生物酶的领域中，将多相催化的边界扩展到生物化学将是非常有趣、新颖和有吸引力的，有助于促进清洁制药和化学品生产的潜在新途径。辅因子 NAD(P)H 是参与催化的关键还原剂。用于药物/化学产品合成的酶还原。这些产品的一个著名例子是立普妥的“阿托伐他汀”（活性成分）（2010 年全球销售额为 119 亿美元），它可以降低心脏病发作和中风等的风险或降低心脏病的危险因素（年龄、吸烟、高血压）。血压等）。 NAD(P)H 的高成本和化学计量的使用使其再生对于实际应用至关重要。现有的再生方法有五种（酶法、化学法、均相催化法、光催化法和电催化法）。令人惊讶的是，至少部分是因为人们对将负载型金属催化剂引入生物化学知之甚少，所以没有人开始认真研究多相催化剂在辅因子再生和相关应用中的潜力。这就是我们计划做的。将对多相催化再生途径和最佳固体催化剂的机理有基本的了解。最终目标是开发一种高效、清洁的辅因子再生工艺，可与生物转化相结合，以药物中间体的酶法合成和二氧化碳转化为代表应用。

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