Awarded BIOCATNET Funding

Below are public summaries for the projects so far funded through the BIOCATNET Proof-of-Concept and Business Interaction Voucher schemes. Public summaries are submitted during the application phase and should then be updated during the final reporting of the project. All of hte projects funded during Rounds 1 and 2 of the Proof-of-Concept scheme have now been completed.

Please click on the links below to jump to specific rounds or schemes:

Proof-of-concept funding:

 


All Proof-of-Concept project proposals are independently reviewed by at least three assessors to ensure fair treatment of all applicants and to avoid conflicts of interest. For the sake of transparency, where an award has been made to an individual or organisation with direct links to the management of BIOCATNET, this relationship is stated in the project summary. Where such a relationship exits that individual or organisation is recused from the review process in that round of funding and additional impartial review of that application is sought.

Round 1

 


All projects awarded in the first round of PoC funding have been completed and final reports have been submitted.

High throughput construction and evaluation of multi-enzyme complex cascades in biocatalysis.
Academic Principal Investigator: Geoff Baldwin, Imperial College London
Industrial Partner: Dr. Reddy’s Technology Centre
Summary

In this project we proposed to develop a multi-enzyme scaffolding platform for rapid library construction of improved expression systems for multienzyme biocatalytic processes. Optimizing cascades of enzymatic processes in biotechnological settings poses a major challenge in the development of novel, efficient and competitive biotransformation workflows. Our aim was to establish an enabling high throughput toolset for the design of complex biotransformations by combining know how in highly parallel and combinatorial DNA assembly for balanced multiple enzyme expression to enhance capabilities in enzymatic biotransformation.

This toolset that we have created through this work extends state of the art DNA assembly and protein expression systems. We have demonstrated that it facilitates the building and testing of complex multi-protein architectures. Gaining precise control over enzyme expression and screening targeted construct libraries is crucial to identify optimal design strategies for scaffolded multi-enzyme expression systems. The work that we have performed in this grant demonstrates the applicability of our toolset to tackling this complex approach. We have here demonstrated that it can be applied to the optimisation of a two enzyme system used in a cell free extract biotransformation with our industrial partners.

ENZOFF – Novel enzymes for the greener manipulation of carbamate groups.
Academic Principal Investigator: Nicholas Turner, The University of Manchester
Industrial Partner: Charnwood Technical Consulting Ltd.
Summary

The use of carbamate protecting groups is ubiquitous in the synthesis of pharmaceuticals, agrochemicals and fine chemicals, especially the use of t-butyloxycarbamate (BOC) and benzyloxycarbamate (CBZ) synthons. In theory, the principals of green chemistry would dictate that the use of protecting groups should be avoided. However in practice, there will always be a need for protection and deprotection, especially in pharmaceuticals, as more complex functionalized structures / semi-synthetics become more prevalent in development portfolios. In pharma/chemical manufacturing, there is a drive to move towards greener and more sustainable bio/chemo catalytic technology to avoid toxic reagents/bi-products and increasingly rare and expensive precious metals. Surprisingly, there has never been developed a broad biocatalyst platform for the green simple hydrolytic removal of these carbamate protecting groups, despite sporadic reports in the literature of this transformation being viable. This POC study seeks to bring together the available information on carbamate –hydrolysing enzymes/whole cells and to start to understand and define what enzymes are responsible and to provide a basis of information and data for a bigger project in the IB Catalyst which would push forward development and commercialization of a general platform of biocatalysts that can hydrolyse BOC and CBZ carbamates. As well as removing the need to use strong acids, toxic reagents and heavy metals, the use of a biocatalyst also provides the possibility of manipulating chiral centres.

NOTE: Nicholas Turner is a Director of BIOCATNET. Andrew Wells is a member of the BIOCATNET Management Board

A targeted ‘omics’ approach for mining microbial genomes for new lignin transforming biocatalysts.
Academic Principal Investigator: Neil Bruce, University of York
Industrial Partner: Prozomix Ltd.
Summary

The concept of biorefining complex lignocellulosic feedstocks, to add extra value to second generation biofuel pipelines through the generation of high value co-products, is a major strategic priority. There is also a growing urgency for lignin utilisation because production of waste lignin will increase with the commercialisation of lignocellulosic biofuels. Elucidating lignocellulose biodegradation and biotransformation activities are therefore critical for sustaining a bio-economy based on lignocellulose.

Mining genomes and metagenomes of organisms and communities of organisms that degrade lignocellulose presents a large and valuable resource for novel biocatalyst discovery. However, the challenges of effectively probing these data are several-fold: Firstly, there can be very low sequence homology between known, well annotated genomes and new (meta)genomes under investigation making identification of genes of interest difficult. This then further increases the difficulty of identifying genes encoding lignocellulose active enzymes from the multitude of genes controlling intracellular processes and other functions that are not of interest. Lastly identifying genes of interest via a purely bioinformatic mining approach has the significant disadvantage of being unable to identify entirely novel functional enzyme groups as it depends on sequence homology to known proteins and genes. Much of lignocellulose mobilisation and modification biochemistry is still poorly understood at an enzyme level. Therefore, the need to identify these enzymes of uncharacterised function is pressing.

In this project we combined a genome mining approach with a targeted proteomics methodology to create a toolkit for the discovery of lignocellulose active biocatalysts. By combining these two powerful approaches we achieved an unprecedented depth of analysis of the secretome of an uncharacterised fungal species Graphium sp. We successfully identified 869 proteins by LC-MS/MS and 760 of these were more abundant during growth on wheat straw as carbon source, compared growth on glucose. Strikingly, 92 proteins were identified as proteins having similarity to Carbohydrate Active Enzyme (CAZy). Potential biocatalyst targets from our libraries have been sent to our industrial partner Prozomix who are in the process of cloning and expressing these genes using their high throughput cloning and expression system. As proof of principle at York we cloned, expressed and purified from our Graphium library a new AA9 lytic polysaccharide monooxygenase (LPMO).

NOTE: Simon Charnock, MD of Prozomix Ltd is a member of the BIOCATNET Management Board.

Round 2

 


All projects awarded in the second round of PoC funding have been completed and final reports have been submitted.

Exploring enantiopure amino acid production using an immobilized enzyme-coupled system.
Academic Principal Investigator: Prof. Dominic Campopiano, University of Edinburgh
Industrial Partner: Dr. Reddy’s Laboratories Ltd
Summary

Enzymes are natural molecules that catalyse reactions. Enzymes are often highly specific and can catalyse many different reactions. By using an enzyme in a reaction instead of a chemical catalyst, it is possible to benefit from the advantages of using enzymes in an industrial context.This coupled enzyme system uses two enzymes to produce one single amino acid product that can be used for the production of more complex compounds. The advantage of this system is that it allows cheap and convenient access to a range of non-natural and potentially expensive molecules and only produces one product avoiding the need for difficult separations. Our group have previously demonstrated the use of this system and developed a high throughput assay for monitoring the coupled enzyme system. [1, 2]In this proof of concept project, the enzymes were immobilised on a solid carrier, removing the enzymes from the liquid by attaching them through chemical interactions onto a solid resin. By removing the enzyme from the liquid, the coupled system can still produce single amino acid products as before but it is very easy to remove the enzyme from the products after the reaction and there is the potential to reuse the enzymes (making the process more cost-effective). While similar systems have been explored before the advantage of our system is that the NAAAR has been engineered to make it a more efficient and industrially relevant catalyst and we have used our system in flow, where the starting material is cycled through the solid resin continuously until it is completely converted.

The outcomes of this project are that a promising solid carrier has been identified for the co-immobilisation of these enzymes and the co-immobilised system has been demonstrated to produce the single amino acid product both in batch and in flow experiments. The potential of this co-immobilisation of the enzymes will be further developed with optimisation of the system to allow for use on an industrial scale.

[1] S. Baxter, S. Royer, G. Grogan, F. Brown, K.E. Holt-Tiffin, I.N. Taylor, I.G. Fotheringham, D.J. Campopiano, An improved racemase/acylase biotransformation for the preparation of enantiomerically pure amino acids, J Am Chem Soc, 134 (2012) 19310-19313.
[2] G. Sánchez-Carrón, T. Fleming, K.E. Holt-Tiffin, D.J. Campopiano, Continuous colorimetric assay that enables high-throughput screening of N-acetylamino acid racemases, Anal Chem, 87 (2015) 3923-3928.

Simplified Biocatalyst Production via Auto-­‐Secretion
Academic Principal Investigator: Neil Dixon, The University of Manchester
Industrial Partner 1: Chirotech Technology Ltd.
Industrial Partner 2: Biocatalysts Ltd.
Summary

Industrial Biotechnology (IB) offers the potential to replace a number of production processes for a wide range of chemicals and products including; plastics, polymers, synthetic rubber, active pharmaceutical ingredients, industrial enzymes, biological­‐based therapeutics, flavours and fragrances and fuels. Currently the production of a number of these products is based upon the use of non-­‐sustainable, non-­‐green petro-­‐chemical feedstocks and chemistry-­‐based production processes. In IB, for example, the use of enzymes or biocatalysts can reduce the environmental impact of a production process, by removing the need for heavy-­‐metal catalysts or excessive organic solvent effluents from production processes.

Industrial­‐scale manufacture of recombinant proteins/biocatalysts, includes a number of steps: i) fermentation of micro­‐organism, ii) cell lysis, iii) cell debris removal, iv) product recovery. The down‐stream processing costs can significantly impact the commercial viability of the biocatalytic product and ultimate application. This proof of concept project sought to simplify the down‐stream processing of biocatalysts, and so reduce the cost and complexity of the manufacture of biocatalysts. The project focused on three areas, i) to understand a recent observation that could lead to a simplified biocatalyst production process, ii) validate the resulting process/technology for the production of industrially relevant biocatalysts, iii) quantify the efficiency of the process and assess the likelihood of industrial application. A potential production process simplification/cost reduction has been identified that could enable a broader uptake of biocatalytic processes/routes by the chemistry-­‐using industries, replacing less environmentally friendly and non‐sustainable feedstocks and processes. The project partners are now working to understand how this phenotypic observation can be harnessed and applied for use in biotechnological process applications. The results from this study are being prepared for publication in the academic literature, and will be further disseminated to interested parties at relevant conferences and meetings.

NOTE: Andrew Ellis, Technical Director of Biocatalysts Ltd is a member of the BIOCATNET Management Board, but is not a named party to the application.

Establishing the rate effects on oxidative bio-transformations by using flow processing.
Academic Principal Investigator: Nikil Kapur, University of Leeds
Other Academic Partners:
John Blacker, University of Leeds;
Nicholas Turner, University of Manchester;
Andrew Livingston, Imperial college London;
Nick Williams, University of Sheffield
Summary

The aim of the project was to demonstrate the feasibility of using hydrogen peroxide / catalase to generate super-saturated solutions of oxygen thereby increase the rate of oxidative enzyme bio-transformations to enable continuous flow processes. The advantages are that it enables safe operation, is greener than current oxidants, can provide more intense processes and might be applicable to a wide range of reactions. Currently these reactions are difficult to use within industry, due to the inherent risks associated with the use of oxygen in batch, raising concerns of safety and the need for expensive processing equipment.

The results of the project demonstrate that running an oxidative reaction to produce benzaldehyde from benzyl alcohol with the necessary dissolved oxygen created from a feed of hydrogen peroxide and catalase is a feasible process.

It has been shown that GOase can operate in continuous flow reactor with residence times that are around 3-4 times shorter that the batch reaction and with higher conversions than in air alone. The controlled feeding of hydrogen peroxide into the reaction containing catalase instantaneously generates oxygen that for a short period of time will exceed its solubility, enhanced having a back pressure regulator on the reactor, and this may enable the GOase enzyme to turnover at the higher rates observed.

A prestigious American Chemical Society Green Chemistry Roundtable Award has been successful and we have succeeded in leveraging both University Impact Acceleration Funding, and from Prof. Kapur’s RAEng Fellowship award, that altogether have allowed us to secure a 1 year PDRA position to which we are currently recruiting. This will allow us to develop mechanistic understanding of the reaction scheme, which will allow us to publish a paper in this area. In addition, we are discussing findings with key companies working in this area, with a view to gaining additional support.

Round 3

 

Predictive sequence-activity landscapes of biocatalysts via random forests and deep learning.
Academic Principal Investigator: Doublas B. Kell, The University of Manchester
Summary

The amino acid sequence of a protein determines its biocatalytic activity. The usual way to envisage this relationship is as a kind of ‘landscape’, in which the XY coordinates illustrate where we are in sequence space, and the height reflects the activity of interest. Our aim is to develop an understanding of the sequence-activity landscape such that we can predict which sequences are likely to produce improved variants, such that we can make and test them.

Whilst the means to generate large variant libraries is well established in our lab, the screening and sequencing of thousands of sequences is not routine. We propose to use flow cytometric cell sorting of cells (FACS) to perform fluorescence-based detection of catalytic activity. This screening platform, based on fluorescent probes or expression of GFP (under the control of a biosensor), will be developed in the project. Once cells of a specified activity have been selected using FACS, these will then be cultured and the plasmid extracted. We will then employ long-read ‘next-generation’ sequencing methods to determine the hundreds of thousands of sequence-activity pairs required.

This sequence-activity data will be used to learn a nonlinear mapping (‘model’) that uses sequence as the input and activity as the output. The model is then interrogated in silico with many millions of candidate sequences, and we choose statistically those it suggests should provide better activities, and continue this iteration as above. In the time requested we anticipate doing three generations.

–‘Smart’ amine donors for efficient and cost-effective scale-up of biotransformation employing ω-transaminases.
Academic Principal Investigator: Elaine O’Reilly, University of Nottingham
Industrial Partner: Key Organics
Summary

Omega-transaminases (TAs) catalyse the conversion of commercially available or easily accessible prochiral ketones to high value optically pure chiral amines, in the presence of a sacrificial amine donor. However, significant challenges associated with shifting unfavourable reaction equilibria towards product formation and by-product inhibition coupled with limited substrate scope, have hampered the widespread utility of ω-TAs for the synthesis of chiral amines.

This research will build upon recent work reported in our laboratory that describes arguably the most efficient approach to date for performing biotransformations involving TAs. The success of the approach is due to spontaneous removal of the by-product, which effectively displaces the reaction equilibria. However, this process requires the use of an expensive diamine donor to achieve these high conversions.

We have now identified a novel low-cost donor that is capable of effectively displacing the reaction equilibrium via a similar mechanism to our previously reported diamine donor. This donor significantly outperforms isopropylamine; the most widely used substrate in industry. We have recently trialled it on a number of small scale biotransformations and achieved excellent conversion of challenging substrates to the corresponding optically pure amine. Our focus now is to optimise the process further and make it more suitable for industrial application. We will work closely with our industrial partner, Key Organics, to assess the feasibility of adopting this process for large-scale biotransformations. All products produced during this PoC study will be made commercially available through Nottingham Research Chemicals (NRC) with the assistance of the Business Partnership Unit (BPU) at the University of Nottingham. This project aims to make the biocatalytic conversion of ketones to amines the most cost-effective, sustainable and efficient methodology for performing this transformation on an industrial scale.

Establishing the potential of biosynthetic urea-­‐synthetases as industrial biocatalysts.
Academic Principal Investigator: Christophe Corre, University of Warwick
Industrial Partner: GSK
Summary

Urea-containing natural products represent a particularly important class of bioactive molecules; examples include GE20372A/B as HIV‐1 protease inhibitors and the pacidamycin antibiotics. In addition 16 synthetic urea‐containing drugs are currently marketed such as the suramin antiparasitic agent and a series of sulfonylurea anti‐diabetic drugs. While the urea moiety is essential for activity and/or proteolytic stability, asymmetric synthesis of urea‐containing chemicals remains a challenge and no biocatalysts are currently available for assembling ureido bonds.

Very recently we have discovered a novel family of urea-containing natural products, the gaburedins, in the soil bacterium Streptomyces venezuelae. Using bioinformatics predictions and molecular genetics, we have established that the gene gbnB is essential for gaburedin production and that GbnB acts as a urea synthetase. Understanding and exploiting the enzymatic mechanisms of ureido-bridge formation is expected to result in the development of new biocatalysts to access a range of urea derivatives.

This proof of concept project aims at establishing the nature of the precursors used by GbnB-like urea synthetases and at determining if these enzymes are still active in the absence of the first biosynthetic enzyme involved in the gaburedin biosynthetic pathway. This work will therefore pave the way to the development and exploitation of whole cell biocatalysts based on GbnB to access valuable urea-containing compounds at an industrial scale.

NOTE: Murray Brown, Principal Scientific Investigator for GSK is a member of the BIOCATNET Management Board, but is not a named party to the application.

Bio CO2.
Academic Principal Investigator: Ray Marriott, Bangor University
Industrial Partner: CTC Ltd.
Summary

This POC project has been established to provide scoping data for a consortium formed to discover and implement novel solutions for the efficient and greener isolation of products from biocatalysed reactions. The project will be focused on single transformation processes using isolated enzymes and whole cells, but could well be applicable to products made from synthetic biology approaches. The key goal of the project is to identify scalable novel downstream processing techniques that will allow fast and efficient separation of product and enzyme residues after enzyme-catalysed/whole cell chemical transformations. Additionally, these new isolation techniques will have the added benefits of generating a more sustainable bioprocess as it will be more energy efficient and less reliant on large volumes of polluting organic solvents. A successful project will allow the consortium to establish the United Kingdom as a leader in innovation in the DSP of biocatalysed/IB processes.

NOTE: Andrew Wells, CTC Ltd is a member of the BIOCATNET Management Board.

Business Interaction Vouchers:

 

Structure-Guided Evolution of an industrial esterase from Bacillus sp.
Academic Principal Investigator: Gideon Grogan, University of York
Industrial Partner: Dr Reddy’s Laboratories (Chirotech Technology Limited)
Summary

Carboxylic acids and esters are extremely important structural motifs within products of interest to the pharmaceutical industry. Chirotech (part of Dr Reddy’s, a global pharmaceutical company) had discovered a bacterial esterase from Bacillus that showed great general utility for the stereoselective hydrolysis of a wide range of esters to carboxylic acids. However in many cases the requirement for the lowest cost process necessitates ‘perfect’ stereoselectivity and high activity for every substrate – this means that engineering this enzyme to improve specific parameters for specific substrates is necessary. The closest structural homologue to this enzyme has 33% identity. Although this allows production of a model based on homology modelling, the active site has a number of unresolved loop regions, and when working with small substrates, these molecules can dock into the active site in numerous positions, making it difficult to identify important residues to target for a rational approach for mutagenesis. The success of a rational engineering programme would be greatly enhanced if the enzyme structure was determined therefore. The award of a Business Interaction Voucher to Professor Grogan, in collaboration with Dr Reddy’s, has allowed the structure of the esterase enzyme to be solved at York. The gene encoding the enzyme was cloned, and the enzyme purified, after which it was subjected to crystallization trials that gave the first ‘hits’, or small crystals of the enzyme that provided promising leads for further investigation. Optimized crystals were then analysed at the Diamond Light Source Synchrotron, in order to obtain data leading to the first structure of the esterase. This, however was only of average resolution, and did not permit details of the enzyme active site to be seen clearly. Extensive further crystallization screens revealed a different crystal form, which gave much improved diffraction results. Data on these crystals have been used to build a structure of esterase at high resolution, revealing the details of the active site that will permit the structure-based engineering of the enzyme for improved properties. The project overall has helped to establish a link between the academic and industrial partner in the area of structure-guided evolution in general, which will extend the scope of enzymes currently employed at Dr Reddy’s and will help to make structure-guided design a part of their biocatalysis strategy in future projects.

Genome Mining for Bacterial Aldehyde Oxidases.
Academic Principal Investigator: Andrew Carnell, University of Liverpool
Industrial Partner: Prozomix Ltd.
Summary

This short Business innovation Voucher project has allowed the establishment and development of a collaboration between Dr Carnell’s Research Group at Liverpool University Chemistry Department and Prozomix Ltd.

The interaction has allowed the two groups to work together to provide preliminary evidence that bacterial genomes can potentially provide new enzymes that may show improved activity for reactions of importance to industry, such as pharmaceutical production and the conversion of biomass derived materials to polymer precursors. The key findings were that bacterial genomes contain enzymes that are likely to be similar to those found in mammalian systems that can carry out a wider range of useful reactions. Genes have been identified within the genomes of these bacteria that code for important ‘chaperone’ proteins that are essential for the successful production of this class of enzymes. In addition, Prozomix have carried out optimization studies in several different E. coli strains for production of this class of enzyme, thus allowing for production of new enzymes in the future. Results from this study will be important in underpinning future use of this class of oxidative enzyme in enzyme cascades and industrial biotechnology approaches to chemical synthesis.

Review on proprietary and non-proprietary protein engineering techniques (from an industrial point of view).
Academic Principal Investigator: Nicholas Turner, The University of Manchester
Industrial Partner: Biocatalysts Ltd.
Summary

The aim of the project is to complete a desk based review of proprietary and non-proprietary protein engineering techniques. Protein engineering is the design of new enzymes or proteins with new or desirable functions. Biocatalysts Ltd produces speciality enzymes for the food, flagrance and pharmaceutical sectors and the need for enzymes with high substrate specificity under highly specific process conditions has increased over the last few years. This review would be the first one for this type, where the focus is on use of protein engineering from an industrial point of view for enzyme discovery and commercialisation. The objective would be to help Biocatalysts determine which protein engineering technologies to invest in either through internalisation of that technology or developing strategic technology partnerships.

Review and Ranking of Biocatalytic Routes for the Sustainable Production of a Number of Organic Compounds.
Academic Principal Investigator: Michael L Turner, The University of Manchester
Industrial Partner: AkzoNobel
Summary

As part of AkzoNobel’s strategic drive to make all the company’s products more sustainable AkzoNobel has commissioned the University of Manchester to carry out a desk-top study.

The study will investigate the potential for utilizing biocatalysis (in isolation or in combination with conventional synthetic organic chemistry) for the more sustainable synthesis of a number of key chemicals identified by AkzoNobel.

Biocatalytic synthesis of a diketone.
Academic Principal Investigator: Gary Black, Northumbria University
Industrial Partner: Robinson Brothers Ltd.
Summary

Robinson Brothers Limited manufactures a wide range of chemical intermediates by classical organic chemistry within their plant in West Bromwich. One of their key products requires the conversion of a starting material (which is under price pressure) to a specific chemical compound, a diketone, used across a wide range of sectors, but principally in agrochemical, flavour & fragrance and pharmaceutical manufacture. The chemical methodology is expensive and generates a significant quantity of waste material. There exists in Nature a section of a microbial pathway that converts a more readily available starting material to the required diketone in two enzyme-requiring steps. In this project, it is proposed (a) to incorporate the two-enzyme steps into a user-friendly microbial cell which will then replace this conversion and (b) to investigate the suitability of this partial pathway to provide a greener alternative route to the diketone.

Enabling metabolic pathway engineering in Clostridium within a new BASIC DNA assembly framework.
Academic Principal Investigator: Geoff Baldwin, Imperial College London
Industrial Partner: Chain Biotechnology Ltd.
Summary

Clostridium is a promising/underexploited host for the production of high value chemicals in industrial biotechnology. Its anaerobic life style is ideal for large-scale fermentation processes and Clostridium species have unique and highly reductive biochemical pathways that produce a variety of two, three and four carbon products. CHAIN Biotech is specialised in redesigning metabolic circuitry within the microbe to produce chemical intermediates in the correct enantiomeric form (proprietary Chiral Switch(TM) technology) for high value markets. This ability to define the stereoselectivity of chemicals provides another key advantage over common production strains currently used in large-scale fermentation and chemical catalysis approaches. While CHAIN HAS already curated a large strain library and identified high value speciality chemicals for production in Clostridium, the abilities to build Clostridium specific plasmid systems and complex libraries of pathway variants are currently limited by the use of classical restriction/ligation cloning. In order to overcome this significant roadblock towards cutting edge genetic circuit construction and the automation of biocatalysis pathway engineering for Clostridium we propose to adopt a novel DNA assembly framework for Clostridium. The Baldwin lab at Imperial College developed the novel powerful Biopart Assembly Standard for Idempotent Cloning (BASIC). BASIC provides a highly efficient method for assembling up to 7 parts in BASIC standard during one simple cloning step and allows the seamless combination of such assemblies in hierarchical assembly schemes to build large enzymatic pathways from prebuilt modules. BASIC was already shown to enable complex library creation for pathways in E. coli and adopted by Dr. Reddy’s for powering their biotransformation platform. We now like to show that BASIC can provide the same powerful genetic toolset for engineering Clostridium strains and establish the foundation for creating fine-tuned pathways and provide CHAIN with the means to automate the metabolic engineering of their Clostridium platform. This will be the first commercial example using the BASIC DNA assembly method in Clostridium and will serve to highlight the benefits of using this open source technology for other academics and companies alike.

Evaluation of alcohol oxidases for preparation of aldehyde intermediates for pharmaceutical manufacturing.
Academic Principal Investigator: Nicholas Turner, The University of Manchester, on behalf of Rachel Heath, Research Co-Investigator
Industrial Partner: GSK
Summary

The use of biological catalysts (enzymes) in place of chemicals can have significant environmental benefits as well as economic ones. This project specifically is looking to replace potentially hazardous chemical oxidation with a safer, greener alternative avoiding the use of harsh chemicals, organic solvents and precious metals. The scope of the enzymes to be used in this study has so far not been exploited. This technology will be applicable to manufacturing pharmaceuticals and other fine chemicals.

Industrial applicability of blue multicopper oxidases to direct methanol fuel cells.
Academic Principal Investigator: Christopher Blanford, The University of Manchester, with Lu Shin Wong, The University of Manchester
Industrial Partner: C-Tech Innovation Ltd.
Summary

This project tests whether copper-containing proteins (enzymes) can take the place of a precious metal in a direct methanol fuel cell (DMFC), a device the produces electricity directly from the reaction of methanol and air. Methanol holds 5–10 times the energy as the same size lithium ion battery, which means that devices (for example, mobile phones) that are powered by DMFCs would last longer or be smaller and lighter.

Our work offers solutions to two problems that prevent widespread use of DMFCs:

  1. DMFCs have separate compartments for air and methanol, but both sides use platinum to speed up (catalyse) how fast the electricity flows. The high cost of platinum prevents DMFCs from being economical. Our enzymes take the place of some of the platinum to catalyse one of the reactions. The enzymes use less expensive and more abundant copper, and work more efficiently than platinum.
  2. When methanol and air cross over from their respective compartments in conventional DMFCs, the fuel is used up but does not produce electricity. This lowers the efficiency. Our enzymes work even when methanol is present, but does not react with it. This means that more of the fuel will generate electricity, and the DMFC will be more efficient overall.

The challenges of this project are to compare enzymes that we can mass produce and modify in our labs to those that are commercially available, but are much more difficult to modify to suit our requirements. We will be testing for lifetime, tolerance against methanol and stability at elevated temperatures. The C-Tech team brings decades of experience with electrochemical energy conversion systems, and industrial-grade test equipment. The Manchester team brings molecular biology and bioelectrocatalysis expertise.