Pushing Heterogeneous Catalysis into Biological Chemistry via Cofactor Regeneration

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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.