Biocatalysis and Biotransformations
The addition of the biocatalysis & biotransformation theme to the UK Catalysis Hub will enable integration into the wider catalysis landscape, with the broad participation of UK catalysis scientists and engineers at the Hub expected to dramatically enhance the scope of biocatalysis research relative to what might be achieved with a stand-alone bid. This added-value will see UK biocatalysis research contributing to major societal grand challenges such as energy, healthcare and sustainable manufacture – part of the overall mission of the Catalysis Hub is to drive research in these areas in the UK over the next 5-10 years.
The biocatalysis & biotransformation theme will be established using the same inclusivity ethos that underpins the existing Hub. This new theme will carry out world-leading research, offering expertise and capacity for translational research to all researchers looking to tackle major challenges in the biocatalysis field. Initial collaborating institutions include: Universities of Cardiff, Queen Mary’s London, Queen’s Belfast, Northumbria, Cambridge, University College London, Bath, Edinburgh, Aston, Bristol, Strathclyde, Sheffield, Leeds, Leicester, Exeter, Liverpool, Oxford, Warwick, Southampton, St Andrews and York.
The 5th theme will be led by Nicholas Turner as PI (Manchester) with the following Co-Investigators who will be responsible for the 5 exemplar projects presented as sub-themes in this proposal:
Project 1: Fundamental & Underpinning Mechanistic Studies on Enzymes. Adrian Mulholland (Bristol) & Nigel Scrutton (Manchester),
Project 2: Integration of Bio- and Chemo-Catalysis into Telescoped Processes. Michael Greaney (Manchester) & Turner;
Project 3: Flow Biocatalysis. Rudolf Allemann and Thomas Wirth (Cardiff);
Project 4: Development of the Next Generation of Biocatalysts. Ben Davis (Oxford);
Project 5: Exemplars for increasing the speed of biocatalyst discovery, development, and application. Gary Lye (UCL).
- Artificial Metalloenzymes: Unlocking New Catalytic Routes to Amines
This project will deliver new catalytic methods for the synthesis of (chiral) amines utilizing artificial enzymes developed in UStA and UoN, materials and chemocatalysis from QUB, and biocatalysis from UoM.
- Development of Continuous Flow Processes for Efficient Transaminase Reactions
ω-Transaminase (ω-TA) biocatalysts are showing great potential for the synthesis of optically pure chiral amines, yet there remain limited examples of their application in industry. While there are a handful of reports describing the integration of these enzymes into flow processes, there is no evidence that this technology can be successfully applied for the conversion of ketones with particularly challenging positions of equilibria (e.g. aromatic ketones). Major barriers include (i) challenging reaction equilibria (ii) low reaction rates (2d at present, 1h required), (iii) productivity (mg/L/h rather than Kg/L/h) and (iv) challenging separations. This project aims to address some of these key issues and develop an industrially targeted continuous flow process that enables the conversion of ketones to high-value chiral amines using ω-TAs.
- Exploring the Catalytic Properties of Heme Enzymes with Non-Canonical Proximal Ligands
To combine state-of-the-art spectroscopic, kinetic and structural methods with advanced computational approaches (QM/MM calculations and MD simulations) to gain a detailed, molecular level understanding of the role of non-canonical His-NMH proximal ligand substitutions in enhancing the catalytic performance of heme-dependent enzymes. Such fundamental mechanistic understanding will lay the foundation for the rational creation of modified and/or novel active site heme environments based on chemically programmed histidine analogues.
Dr. Anthony Green
- Integrated flow electrosynthesis / biocatalysis
We will integrate electrosynthesis and biocatalysis in flow for the rapid production of chiral molecules, creating a new type of catalysis platform for sustainable synthesis.
The project will involve several disciplines within chemistry (biocatalysis, physical electrochemistry, flow technology), and links outward to Hub activities such as reactor design, flow engineering, catalyst design, and new chemical transformations. Ultimately, our aim is to process bulk commodity chemicals into chiral building blocks through the integration of electrosynthesis and biocatalysis in innovative ways.
2018 Projects (continuing Projects)
- Modelling and Simulation for Biocatalyst Design and Engineering in the Hub. VanderKamp (Bristol 2 years)
- Synthetic Protein Metalloclusters – Hanging Catalytically Exciting Metals from Precise Sites. Hutchings (Cardiff), Davis (Oxford) ( 2years)
- High-throughput selection method for extracellular biocatalysts. Dixon, Grogan Turner (Manchester 2 years)
- Flow Biocatalysis. R. Allemann (Cardiff, 1year
- New boundaries in fluorine biotechnology. D. O’Hagan (St Andrews, 1 year),
- Monooxygenase Biocatalysts for the Sustainable Manufacture of Lactone Monomers and Novel Lactone-based Polymers for Healthcare Applications. Prof Nigel Scrutton (Manchester 1 year).
- Understanding the reactivity of ferryl heme, and its role in biocatalysis. E Raven (Leicester).