Biocatalysis is a sustainable technology that harnesses the power of Nature's catalysts, known as enzymes, to perform chemical reactions. Enzymes are inexpensive, biodegradable, produced from renewable feedstocks, operate under environmentally benign reaction conditions and speed up chemical processes with remarkable efficiency and selectivity. For these reasons, the chemical and pharmaceutical industries routinely use certain classes of enzymes in commercial manufacturing processes to replace chemical transformations that are inefficient and/or have a high environmental burden. For example, engineered enzymes are now used to produce pharmaceuticals and agrochemicals, recycle plastics and capture carbon dioxide from the atmosphere, thus contributing to a more efficient and sustainable chemical industry. However, enzymes found in Nature are usually not suitable for use in industrial applications and must first be optimized to improve properties such as catalytic efficiency, selectivity, and stability. Directed evolution is a powerful and versatile technology for adapting enzymes to make them suitable for use in commercial processes, but it is a costly and time-consuming process that requires specialist instrumentation only available in a handful of labs. Moreover, many chemical processes use non-natural reactions for which there are no known enzymes that can serve as starting templates for optimization. In this application, we will establish The International Centre for Enzyme Design (ICED), bringing together world leaders in computational protein design, enzyme engineering and industrial biocatalysis, to change the way that industrial biocatalysts are developed in the future. ICED will establish a fully integrated computational and experimental program, integrating the latest deep learning protein design tools with advanced experimental methods for enzyme engineering, to allow the reliable and predictable design of new and improved enzymes with a wide range of useful activities. In this way, ICED will deliver a step-change needed in the field to allow the rapid design of customized biocatalysts in response to diverse societal needs.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

High performance fibres and synthetic textiles are used in large quantities in both industrial and consumer products. They are produced from petrochemical sources and are rarely biodegradable. Whilst some are in principle recyclable, laundry operations lead to uncontrolled release of microplastic pollution into the environment, including the oceans. Natural fibres, such as cotton, make significant demands on land and water use, and have limited mechanical properties. This project will develop an entirely new approach to manufacturing fibres by spinning them from designer proteins grown by microbial fermentation. The resulting materials will be sustainable, biodegradable, and re-processible. Proteins are large natural molecules built out of exact sequences of amino acids; they play essential structural and functional roles in all known life forms. The specific atomic structures mean that the protein chain folds into a precise and unique 3D shape, rather like a 3D jigsaw puzzle. The size and shape of proteins is much better defined than any conventional polymer (manmade plastic). It is these different shapes that give proteins their individual functions. Recent advances in computational protein design allow specific architectures to be designed deliberately. In combination with improved methods to produce large quantities of these proteins, it is now possible to imagine designing bulk macromolecular materials, with much greater accuracy than existing products. Nature makes effective use of intermediate length scales between individual molecules and extended structures big enough to see. Currently, our synthetic materials are poorly controlled in this range. By designing specific protein sequences, we can create self-organising units that simplify both protein production and the process of spinning useful fibres. These units automatically align and pack, increasing mechanical performance, whilst retaining the attractive features of natural protein fibres, which make them so comfortable to wear. Existing attempts to develop this idea have used versions of natural proteins that are extremely difficult to convert into high quality textiles, using conventional bulk manufacturing processes. This project uses newly designed motifs, created from first principles, in order to resolve the crucial obstacles at each step of the supply chain from fermentation, through fibre spinning, to textile conversion. The project will demonstrate the scalability of each step, and produce physical fabric samples. This demonstration, together with key data on production yields and textile performance, will underpin further investment in this revolutionary technology, within the UK. Crucially, the technology will disrupt with existing textile supply chains, allowing new environmentally sound local production. This highly interdisciplinary project will bring together structural biology, synthetic biology, computational protein design, and materials science to create a paradigm shift in fabric manufacturing.

Two major challenges for the textile industry in the transition to clean production are developing new ways to make textile materials and finding alternative applications for waste. This research focuses on leather production; using industrial biotechnology to upcycle waste polymers from textile fibres into mycelium leather. Leather is a very specific sector of the industry that is particularly unsustainable; it requires extensive natural resources, contributes to greenhouse gas emissions, and releases hazardous chemicals into wastewater during tanning and processing. Despite these issues the demand for leather goods continues to grow with the global market thought to be worth around US$394 billion. In the last decade industry has begun searching for sustainable alternatives to animal leather and designers and innovators have begun to look at materials that can be produced through biological fermentation such as bacterial cellulose and mycelium leather. Mycelium leather is seen as a valid alternative to traditional hide leather and products are available on the market such as Mylo (Bolt Threads) and used by fashion designers and companies such as Stella McCartney and Lululemon. Waste textiles remain an industrial challenge, with 73 % of all textile waste sent to landfill or incinerated in the UK. Traditional recycling routes are not appropriate for all textiles due to either their fibre composition or chemicals components, therefore new uses for these surplus materials are required. The conversion of surplus textile waste into a high value product such as leather-like materials positions industrial biotechnology in the centre of the circular economy for the textile industry. This project ultimately aims to develop a platform that utilises industrial biotechnology to upcycle waste polymers from textile fibres. We propose to develop enzymatic pre-treatment cocktails capable of degrading waste cotton, polyester / polyethylene, Nylon and (to make this process truly circular) mycelium leather to a nutrient solution capable of sustaining mycelium growth. Therefore, the discovery of new enzymes capable of degrading textile waste and forming enzyme and additive cocktails is a critical aspect of the research. This will be completed through the following main tasks: 1. Identification of enzymes using an "Omic" approach from textile waste and recycling sites and a review of the types of wastes available at those sites. 2. Characterise those enzymes identified and combine with previously characterised enzymes (some in-house) to form pre-treatment cocktails capable of waste textile degradation to produce a growth substrate. 3. Test the ability of the growth substrate produced to sustain fungal growth. 4. From this fungal growth produce a mycelium leather product and test its physical properties to compare to traditional mycelium leather. This project will be carried out in collaboration with a number of project partners and stakeholders that have a vested interest in mycelium leather. Waste and recycling sites will provide access to textile only and textile rich landfill sites for "Omic" sampling, Prozomix will supply enzyme solutions for testing alongside newly discovered enzymes and MyKKO will incorporate the substrates into their production facility, as well as testing of the mycelium leather produced. By bringing together these stakeholders alongside this project, this project will look to move the production of mycelium leather closer to an industrial process providing a low-cost feed stock for mycelium production.

In the ever developing world of pharmaceuticals and treatments of diseases new, more challenging drug targets are being identified that require ever more complex drug molecules. These complex molecules or "New Modalities" bridge the gap between the two existing classes of compounds, small molecules (e.g. Aspirin) and biologics (Antibodies), and are typically larger than the existing small molecules but smaller than traditional biologics. These new classes of molecule offer great promise as novel therapies and indeed many of these medicines are aimed at biological targets that cannot be addressed by traditional either small molecule or antibody derived drugs. The complexity of the new modalities currently results in high cost of manufacture which offers an opportunity to develop lower cost routes to produce these compounds. Small molecule manufacturer has benefited from adopting biocatalysis within manufacturing strategies and has demonstrated the potential for use of these catalysts in wider chemical manufacture, such as reduced waste streams, lower energy costs and reduced costs of goods including solvents. Indeed, the project partners have already generated some early proof-of-concept studies, backed up by a wider literature evidence base suggesting that biocatalysis can be used in the synthesis of these new modalities. Through the partnership of the University of Manchester, AstraZeneca and Prozomix we are bringing together a diverse range of experts that will facilitate the development of new manufacturing strategies to produce these new modalities in an efficient and cleaner manner. The use of biocatalysis has the potential to allow access to chemistries and control of manufacture that are otherwise unavailable to the pharmaceutical manufacturing community. Culminating in lower cost manufacturing that translates into greater access to the next generation of drug for a wider community.