Pushing Heterogeneous Catalysis into Biological Chemistry via Cofactor Regeneration

多相催化剂被认为是化学转化的主力，在90%以上的工业过程中都有涉及。尽管多相催化与传统合成路线相比具有许多优点，但仍有一些主要的不足之处。例如，尽管有大约200年的历史，但到目前为止，大多数使用多相催化系统的工业过程和研究都集中在相对较小的分子（例如氨合成，费托法，天然气重整和水煤气转移反应）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）。并且忽略了作为反应物或产物的大分子生物分子（如酶辅因子）（在这种情况下，“非均相”是指传统的固体散装相或负载金属催化剂，而不是固定化酶或模拟物）。在传统上被认为属于生物酶的领域将多相催化的边界扩展到生物化学将从根本上是有趣的，新颖的和有吸引力的，为清洁制药和化学生产提供了潜在的新途径。辅助因子NAD(P)H是参与药物/化学产品合成的酶还原的关键还原剂。这些产品中一个值得注意的例子是立普妥（Lipitor）的“阿托伐他汀”（活性成分）（2010年全球销售额119亿美元），它可以降低心脏病发作和中风等的风险，或降低心脏病的风险因素（年龄、吸烟、高血压等）。NAD(P)H的高成本和化学计量的使用使得它的再生在实际应用中必不可少。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，至少在一定程度上，由于在将负载金属催化剂引入生物化学方面的知识很少，没有人开始认真研究非均相催化剂在辅助因子再生和相关应用中的潜力。这就是我们计划要做的。对多相催化再生途径的机理和最佳固体催化剂有了基本的认识。最终目标是开发一种高效清洁的辅助因子再生工艺，可以与生物转化一起工作，以酶促合成药物中间体和二氧化碳转化为代表的应用。

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.