Our project, Novel Biocatalysts for Sustainable Manufacture of Pharmaceuticals, is developing a greener, safer way to produce important pharmaceutical chemicals. Traditional chemical processes for adding nitro groups to molecules require harsh conditions and generate hazardous waste. We are replacing these methods with enzymes called nitrating cytochrome P450s (NCP450s), which can perform the same transformations under mild, water-based conditions. A key challenge is producing these enzymes consistently at high quality. The enzymes need a molecule called heme to function properly, and standard production methods can result in a mixture of active and inactive proteins. This variability makes it difficult to scale up the process for industrial use. To solve this, we are working with the Centre for Process Innovation (CPI) to identify the best microbial hosts for producing fully functional NCP450 enzymes. By testing different bacteria, including specially engineered E. coli strains and naturally heme-producing species, we aim to find a system that reliably produces large amounts of active enzyme. This will ensure our biocatalysts perform consistently and can be scaled up safely and efficiently. The project will generate new knowledge about which microbes are best suited for producing these enzymes, develop methods to measure enzyme quality accurately, and provide practical guidance for industrial use. These outputs will strengthen our existing programme, support regulatory compliance, and accelerate the adoption of environmentally friendly manufacturing processes in the pharmaceutical industry. By overcoming this bottleneck, our work will help make pharmaceutical manufacturing safer, more sustainable, and less wasteful, supporting the UK's leadership in green biomanufacturing and innovation.

ErebaGen harnesses chemistry from Nature and its project aims to transform hazardous chemical manufacture through the use of sustainable biological processes. The innovation focus and need is aromatic nitration, a critical chemical step in production of numerous pharmaceutical intermediates. This reaction proceeds rapidly, generates heat, can get out of control risking explosion and formation of unwanted by-products. The process uses hazardous chemicals such as concentrated acid, with associated risks of disposal or leaching. Despite this ~20% of all synthetic pharmaceutical intermediate processes involve nitration. Consequently many are produced abroad, or by multi-step synthetic routes to avoid nitration, increasing cost and time. ErebaGen is responding to the need using our innovative technology platform that harnesses bacterial enzymes evolved by nature over millions of years. Distinctively ErebaGen uses a patented activator to switch on specialised metabolism, that is the synthetic processes not required for survival of the microbes.. This gives ErebaGen a competitive advantage: access to a large, chemically diverse, promiscuous pool of enzymes with flexible substrate tolerance. It is combined with bioinformatics, genomic and chemical analysis and automation. The intellectual property comprises the patented activator and substantial confidential know-how including proprietary software Customers are pharma/biotech companies but our innovations have broad application in agrochemicals, flavours and fragrances, dyes and fine chemicals; the project could open up these markets. ErebaGen's approach can be expanded to a range of other hazardous/inefficient chemical processes. The project brings together a diverse, experienced team from Erebagen, partner CPI and subcontractors National Physical Laboratory, Peritus Regulatory and Sterling Pharma, plus individual experts. We have a two year project plan to demonstrate that enzymatic aromatic nitration is a cost-effective, sustainable alternative to chemical nitration. Performance measurements and comparative assessment will assess this potentially transformational alternative to traditional synthesis. The project deliverables will help ErebaGen secure higher value partnerships, which will take its innovation through to market.

Resistant strains of bacteria, fungi and plants that are not susceptible to modern medicine and crop protection chemicals, pose a serious threat to society. The rise in antibiotic resistant superbugs, drug-resistant cancers and treatment-resistant crop pests are all threatening to have a major impact on our health, quality of life and ultimately the sustainability of life as we know it. To combat this growing threat we need new chemical compounds that are able to selectively kill these resistant organisms and act as the medicines and crop protection chemicals of the future. Identifying new compounds that have good bioactivities is hard. Typically companies need to screen 100,000 compounds to find one structure that hits a desired target. This low "hit rate" makes discovering new medicines and crop protection chemicals slow and expensive. We have developed a platform which enables us to engineer soil bacteria to produce new bioactive natural product compounds that have hit-rates 20x-better than synthetic chemicals currently being used by industry. Through our market research we have identified several companies in both the pharmaceutical and agrochemical sectors who are keen to partner with us to discover new natural products that could be developed into new medicines and crop protection compounds. We will use this funding to better develop our platform and to demonstrate that we can build new compound libraries quickly and affordably. We will achieve this by automating the platform with robotics, which will allow us to engineer more bacteria in parallel and decrease the time the platform takes to complete a discovery cycle. As we develop the platform we will generate new libraries of natural products that will enable us to partner with early adopters of our technology. Our aim is to grow these early adopter partnerships into deeper, long term co-development projects with a focus on bringing new medicines and crop protection products to market.