Pushing Heterogeneous Catalysis into Biological Chemistry via Cofactor Regeneration
Lead Research Organisation:
Lancaster University
Department Name: Engineering
Abstract
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.
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.
Publications
Burnett J
(2022)
Directing the H 2 -driven selective regeneration of NADH via Sn-doped Pt/SiO 2
in Green Chemistry
Burnett JWH
(2022)
Supported Pt Enabled Proton-Driven NAD(P)+ Regeneration for Biocatalytic Oxidation.
in ACS applied materials & interfaces
Li J
(2024)
Oxide-supported metal catalysts for anaerobic NAD+ regeneration with concurrent hydrogen production
in Chinese Chemical Letters
Description | The project was funded by EPSRC's inaugural New Horizons scheme, a pilot programme for researcher-led, creative, and high-risk research. In this project, we have demonstrated that conventional heterogeneous supported metal catalysts (e.g., platinum on silica) can promote biological cofactor regeneration reactions, an area traditionally seen as belonging to biological enzymes, or other types of catalysis. The results have established the concept of Bio-Hetero Catalysis. We have also developed an in situ spectroscopic method for monitoring the progress of reactions. This in turn allowed us to establish of a platinum-tin bimetallic catalyst, which delivered the highest reported selectivity (i.e., 90%) thus far. The project has enabled us to lead the advancement of the field. The knowledge advanced could be used in the decarbonisation of biotechnological, chemical, and pharmaceutical sectors, where contributions to overall process sustainability and net zero may be expected. |
Exploitation Route | We envision that further work on bridging the gap between the laboratory and end users will be beneficial. The theory and fundamental research developed here are not ready yet to be employed as a solution by users. |
Sectors | Chemicals Energy Environment Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
Description | An exemplar project of EPSRC The UK Catalysis Hub |
Amount | £119,992 (GBP) |
Organisation | Research Complex at Harwell |
Department | UK Catalysis Hub |
Sector | Public |
Country | United Kingdom |
Start |
Description | An exemplar project of EPSRC The UK Catalysis Hub |
Amount | £47,225 (GBP) |
Organisation | Research Complex at Harwell |
Sector | Public |
Country | United Kingdom |
Start | 12/2023 |
End | 11/2024 |
Description | New Route to Zero Carbon Hydrogen |
Amount | £202,264 (GBP) |
Funding ID | EP/X018172/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2023 |
End | 07/2025 |
Description | Covalent organic networks for enzyme entrapment |
Organisation | University of New South Wales |
Country | Australia |
Sector | Academic/University |
PI Contribution | Our team in the UK have contributed to the enzymatic catalysis part. |
Collaborator Contribution | The team in Australia have contributed to the synthesis of covalent organic networks. |
Impact | Covalent organic networks for in situ entrapment of enzymes with superior robustness and durability, Chemical Engineering Journal, Volume 450, Part 4, 15 December 2022, 138446. |
Start Year | 2021 |
Description | Hetero-Bio Catalysis for Bio-economy |
Organisation | University of Kansas |
Country | United States |
Sector | Academic/University |
PI Contribution | Based on the techniques developed in this project, we have formed the partnership aiming to establish for a NSF Global Center for Bio-economy. |
Collaborator Contribution | Working together now for a bigger grant. |
Impact | not having anything yet, it is in progress. |
Start Year | 2023 |
Description | NAD-Dependent Bio-oxidation |
Organisation | Manchester University |
Country | United States |
Sector | Academic/University |
PI Contribution | We have joined forces to explore applications of technologies developed in this project. |
Collaborator Contribution | Biocatalysis |
Impact | not yet, it is in progress. |
Start Year | 2023 |
Description | Tandem Catalysis |
Organisation | University of Utah |
Country | United States |
Sector | Academic/University |
PI Contribution | We have used our expertise and equipment in Lancaster to generate new catalytic materials that can be used in our partner's research, bringing synergetic results. |
Collaborator Contribution | They have used their expertise and equipment to test the catalysts developed in Lancaster, exploring new applications. |
Impact | This is a multi-disciplinary collaboration where engineering, chemistry and biology have been involved. The collaboration has currently led to a couple of grant proposals submitted (pending for decisions) and a joint paper submitted (being revised after review). |
Start Year | 2021 |
Description | UK Catalysis Townhall Meeting |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | Joined discussions of UK Catalysis experts about what UK Catalysis Hub Phase 3 should look like. |
Year(s) Of Engagement Activity | 2024 |