Public Funding for Ingenza Limited

Our project addresses the critical need for viable, sustainable biomanufacturing processes and accelerated development of protein therapeutics, emphasising the importance of predictability when designing DNA sequences to produce valuable heterologous proteins efficiently, using recombinant organisms. Leveraging insights from natural codon usage profiles, we developed codABLE, a machine learning-based platform to customise genetic codon composition to be most compatible with the production host. CodABLE outperforms codon optimisation algorithms operated by commercial DNA synthesis providers and offers a unique advantage in controlling protein expression without altering regulatory regions such as promoters or ribosome binding sequences. Initially applied to _Bacillus subtilis_, codABLE demonstrated repeated success in predicting and enhancing protein expression. Now, we aim to extend this algorithm to _Pichia pastoris_, a more complex eukaryotic organism with particular advantages for use in protein biomanufacturing. Expression data from a large and diverse library of gene variants will be collected by fluorescence activated cell sorting (FACS) and Next Generation Sequencing, to establish a genotype-phenotype relationship. These valuable data will be fed into our machine learning platform, incorporating algorithms like Support Vector Machine and Random Forest, to discern key relationships between codon usage and protein expression. The best-performing algorithm will be used to design DNA sequences to express protein targets of commercial value, serving as both model validation and a compelling solution for those seeking innovative protein expression strategies. Our approach combines cutting-edge computational technology with Ingenza's expertise using diverse microbial hosts and ultra high-throughput FACS screening to increase our business competitiveness and contribute to Scotland's bio-based manufacturing innovation.

Amprologix is a company developing novel antibiotics to meet the global threat of antimicrobial resistance (AMR). AMR happens when bacteria become resistant to antibiotics and results in treatment failure and increased death from 'drug resistant' infections. These infections killed over 1.2 million people in 2019 and new antibiotics are urgently needed. If we don't develop new antibiotics, our current medical system may fail and things like cancer therapy and routine surgery may result in a fatal infection. In this TOBRADERM project, Amprologix will test a new antibiotic compound, epidermicin NI01, for treating skin infections, which affect millions of people every year in the UK and are the cause of more than 10% of all antibiotic prescriptions. Skin infections can be minor but can also result in severe and fatal outcomes, and they are increasingly complicated by AMR. We will develop epidermicin to be used externally (topical application), being applied directly to infected areas. This increases the killing action but also helps preserve current antibiotics, taken orally or by injection, for use against serious infections, like those in the blood. Epidermicin NI01 is from a new class of antibiotic compound, the bacteriocins (small protein-like molecules). Whilst bacteriocins are not used to treat patients yet, epidermicin has many features that increase the chance of it being a successful drug. These features include properties that minimise any risks that have stopped development of previous bacteriocins: it has very potent activity against globally leading pathogens ('superbugs'), including those that are resistant to current antibiotics and the leading causes of skin infections; toxicity is extremely low, even in recent safety tests in animals; resistance is very unlikely to occur due to the novel way it kills target bacteria; and we have developed an extremely low-cost production system. Epidermicin will also not kill all kinds of bacteria meaning it will target the main pathogens, leaving other skin bacteria unharmed, protecting the 'microbiome'. Epidermicin is an extremely promising new antibiotic and success in the TOBRADERM project will allow Amprologix to access new drug markets, helping it grow into a global leader in 'topical therapeutics'. This will create jobs, generate income for the company and enable development of a new drug to treat skin infections, potentially benefitting over 1 million people a year in the UK.

no public description

This project will apply world-class biotechnology to deliver the world's first bio-based commercially viable manufacturing process for methacrylate ester (MAE), the building block of poly-methylmethacrylate (Perspex(r)) with a game-changing improvement in sustainability. The collaboration of Mitsubishi Chemical Corporation (MCC --Japan), Lucite International, its UK headquartered subsidiary and UK based biotechnology SME, Ingenza Ltd thereby brings disruptive innovation to a product, currently manufactured solely using unsustainable feedstocks and chemical manufacturing processes. As market leaders with a one-third share of the annual global 3.7 million tons ($6.7bn) methacrylates market, MCC and Lucite possess unrivalled knowledge of the market potential and needs, as well as process scale-up and engineering expertise to provide a compelling route to market and a sound business plan for the project outputs. MCC's corporate vision demands a rapid realisation of biobased methacrylates being brought to the market, thereby fulfilling its sustainability commitments according to the corporation's KAITEKI principles of lower dependence on fossil fuel raw materials, reduced water consumption and overall lower carbon footprint. Ground breaking technology, including fluorescence activated cell sorting (FACS) based screening will select isolates of the microbe used in this fermentation based manufacturing process, meeting required performance criteria of product tolerance, productivity, operational robustness and feedstock conversion efficiency. The project will deliver the optimised production organism and a validated, scalable bio-manufacturing process that de-risks post-project progression to commercial piloting, in preparation for cost-competitive, sustainable manufacturing of one of the world's most important and versatile durable polymers. The project thereby aims to deliver a world-leading example of commercial industrial biotechnology success. _PERSPEX_(r) is a registered trademark of _Perspex_ International.

Carbon utilisation in bioethanol production by the yeast _Saccharomyces_ _cerevisiae_ suffers significant efficiency losses because the organism also produces glycerol as a (waste) co-product to help maintain its osmotic balance. This low value waste product compromises bioethanol yield by up to 5%. Others have tried to address this problem, employing yeast bioengineering to reduce glycerol production and redirect more feedstock carbon instead to ethanol. The approach has achieved partial success, increasing carbon efficiency and maintaining cellular reduction-oxidation (REDOX) balance. The limitation of earlier approaches is that the intermediates of the engineered metabolic pathway to ethanol can be converted to other cellular metabolites, such that the full carbon redirection benefits cannot be realised. Our innovative approach provides key advantages over that of our competitors. It will similarly reduce glycerol synthesis but instead redirects carbon to ethanol via an alternate intermediate which is not otherwise metabolised, thereby potentiating maximal carbon use efficiency and ethanol productivity gains. Ingenza has conducted yeast bioengineering for over 10 years, developing all necessary expertise, enabling technology tools and capabilities to deliver this project. Our go-to-market strategy involves the commercialisation of project outputs under an existing technology license relationship with a major international partner. We will safeguard our project outcomes through patent protection and the partner's policing. The potential return on project investment represents significant value for both Ingenza and UK taxpayers. The global bioethanol market is dynamic with (until recently) 5.3% CAGR (2014-2019) and usage in 2019 of 29 million gallons globally. While we recognise that there are alternative opportunities for the technology in many markets (e.g. beverage alcohol) the bioethanol market alone is expected to be valued at $79.6 billion by 2024\. Successful deployment of the project technology could secure significant returns for Ingenza, underpinning job protection and investment in future growth initiatives. The project will allow a leading UK developer of industrial biotechnology to aggressively participate in a synergistic commercial collaboration to deliver disruptive technology that expands the use of sustainable liquid fuels and advances the UK bioeconomy more broadly, to positively impact climate change and environmental sustainability.

Oesophagogastric cancer (cancer of the food pipe and stomach) is the fifth most common cancer in England and Wales with 16,000 new cases diagnosed every year. Currently only 15 out of every 100 patients diagnosed with this type of cancer live beyond 5 years. When oesophagogastric cancer is detected it is often in an advanced late stage. This is because symptoms associated with early disease are typically vague and common to a number of benign (non-cancer). It is not possible for GPs to send all patients who present with such symptoms for endoscopy, a 'camera test' to confirm the diagnosis of cancer, as this test is expensive and uncomfortable for patients. It is therefore important to develop new acceptable, accurate and affordable tests to help detect oesophagogastric cancer at an early stage. To address this problem, we are developing a non-invasive breath test for oesophagogastric cancer. The test is based on the detection of small molecules in exhaled breath called volatile organic compounds (VOCs). Our research has suggested that bacteria within the stomach of patients with oesophagogastric cancer are at least partly responsible for increased production of VOCs. This study intends to investigate the role of stomach bacteria in VOC production in oesophagogastric cancer. We will grow bacteria collected from cancer patients and measure their production of VOCs using mass spectrometry. We will conduct further experiments exploring what factors affect the production of VOCs from bacteria including the effects of growing bacteria and cancer cells together. Studying VOC production in this way will help us to understand how they are produced. This research is important because it can explain the underlying science behind a potentially innovative, non-invasive and cost-effective breath test to detect patients at risk of oesophagogastric cancer. Early diagnosis and treatment will lead to improved survival rates with global economic and societal benefits.

This project will have a disruptive impact on the sustainability and cost effectiveness of ethanol production for the renewable fuels sector, while improving the environmental footprint and climate-change impact of the entire ethanol industry. It will address multiple economic, social, environmental and political needs. It will achieve this through innovative synthetic biology based, carbon-abatement that significantly reduces the normal concomitant emission of carbon dioxide (CO2) as a by-product of ethanol biosynthesis from crop feedstocks. To achieve this aim we will engineer _Saccharomyces cerevisiae_ (Brewer's yeast) to consume 'green hydrogen' as an energy source in order to allow feedstock carbon (that would normally be emitted as CO2) to instead be redirected to ethanol biosynthesis. The primary goal is a truly net zero ethanol fermentation that emits no CO2\. Global yeast-based bioethanol production in 2019 of 28.6 billion gallons (BioFuel Digest 2020) emitted 77.6 million tonnes of CO2 GHG into the environment. By redirecting carbon from CO2 to ethanol we will lower emissions and crop feedstock requirement per unit ethanol produced, freeing up agricultural land for food and feed production. This will underpin political ambitions to increase bioethanol use in transportation fuels, addressing environmental and economic challenges and supporting UK government legislation to increase fuel-ethanol content from E5 to E10 and beyond. The resulting reduction in crop feedstock requirements (up to 33%) will provide market-leading competitiveness. The efficiency and sustainability gains of the resulting engineered yeast will be applicable to further bio-based products and the project aligns fully with the government's Clean Growth Strategy and net zero emissions targets. This project leverages the expertise and end-user relationships of an established and successful UK industrial biotechnology company to implement a disruptive technology that would establish industry-leading product competitiveness alongside potential annual carbon abatement of 77 million tons to establish a leading position in the provision of industrial yeast to the 30 billion gallons/£29 billion global markets for fuel ethanol.

no public description

This project aims to support a novel and vital alternative strategy to realise broad population immunity to the SARS-CoV-2 virus (the cause of COVID-19 disease) in the event that the adenoviral-based vaccines currently under development in the UK prove insufficiently efficacious, safe and/or cost-effective. It will show that yeast-based production of a key viral protein fragment (antigen), that has proven immunogenic in feasibility studies when linked to a novel Virus Like Particle (VLP), provides a rapidly scalable, highly cost-effective and versatile means to enable widespread vaccination of the UK and global population. Crucially, whereas the VLP can be readily produced in the bacterium _E. coli,_ the viral protein fragment is unsuited to production in bacteria and has only been prepared in cultured human cells, a method that cannot be cost-effectively scaled-up for clinical trials and full scale manufacture. However, the yeast _Pichia pastoris_ can produce complex mammalian proteins efficiently, enabling rapid scale-up and highly cost effective production. Ingenza recently engineered _Pichia_ to prepare novel antibacterial proteins to high purity by optimising their production, purification, testing and yield from _Pichia_, using an innovative manufacturing platform called "visABLE" which enables selection of the most productive and stable _Pichia_ recombinants and recovery of their heterologous target protein. In this project we will repurpose visABLE to deliver a recombinant _Pichia_ strain to rapidly prepare and supply the viral antigen, that will be combined with the novel VLP developed by researchers at Oxford University for efficacy testing. If comparably immunogenic, the _Pichia_ production system will permit rapidly scalable, highly cost-effective and cGMP-compliant manufacture of this vaccine component, thereby accelerating the development, testing and availability of a vital alternative to current COVID-19 vaccine production systems in development as well as providing a versatile and novel platform to enhance future UK viral responsiveness. Effect of Extension for Impact funding 21-10-20: This project successfully produced the intended SARS-CoV-2 spike-RBD antigen using the yeast P. pastoris. In rigorous immunogenicity testing by Oxford University in a validated mouse model of vaccine efficacy, the P. pastoris derived RBD proved to elicit at least as strong immunogenic efficacy as RBD produced using more expensive and less adaptable mammalian cell production systems. This critical demonstration underpins future work to realise anticipated major cost, adaptability and reusability benefits of the P. pastoris derived vaccine. Continued process optimisation and scale-up of the bio-manufacturing process by this team can ensure development of what could prove to be a vaccine platform of great importance in the fight against the on-going coronavirus pandemic and other major viral diseases.

This project aims to demonstrate the significant safety and cost benefits of a novel enzyme-enhanced test-strip that rapidly substantiates the correct placement of nasogastric feeding tube in infants and neonates - patient sub-groups for which tube placement errors confer very significant clinical risks and costs. Several hundred thousand nasogastric (NG) feeding tubes are used by the NHS every year in paediatric and neonatal care. Tube misplacements in all patients can and do have disastrous consequences, including patient death. Current safety guidelines and standard UK hospital practice require a test for NG tube aspirate to show pH5.5 or lower prior to feeding or medication, intended to indicate correct stomach location by the presence of gastric hydrochloric acid. The pH test-strips currently employed to this end solely measure gastric HCL and are frequently misinterpreted. This limitation of the only bedside assay currently recommended by the NHS, results in unneccesary confirmatory chest X-rays which, quite apart from being particularly undesirable in infants and neonates, are themselves susceptible to further misinterpretation. In addition to greater clinical risks, the costs are also disproportionately high for this vulnerable patient group. We have developed a novel enzyme-enhanced test-strip to verify correct tube placement which, in recent studies on adult patients in UK hospitals, has proved to be significantly more reliable and accurate than current recommended NHS practice, while lowering costs and requiring no extra user training. The test-strip is innovative in detecting the activity of stomach-specific Human Gastric Lipase enzyme (HGL) to augment the acidic pH response of gastric acid and thereby provide a far more sensitive and selective means to confirm safe and correct NG tube placement. This project will further validate the technical performance of this new test-strip in the infant patient sub-population to quantify its capability to reduce clinical risks, costs and length of hospital stay. Greatly improved safety and reduced confirmatory X-rays in UK paediatric care will prove highly beneficial to the adoption of this new test overseas. Whereas NG tube placement practice worldwide varies greatly for adults, the repeated exposure of infants and neonates to X-rays is universally considered unacceptable. The project will include a non-invasive clinical trial within the paediatric ward at St. Mary's hospital, Paddington, London. Data on clinical utility and health economics will be collected to assess the positive impact of the new test-strip's application and further promote its adoption by the NHS and healthcare providers worldwide.

"Bio-inspired processes will have a major impact on the challenges of the global society in 21st century, including those associated with environmental sustainability. The employment of biocatalysts in industrial processes is expected to boost a sustainable production of chemicals, materials and fuels from renewable resources. The scope of this proposal is to encourage and translate academic research and its outcome into a novel industrially usable platform for the sustainable production of scientifically improved biomaterials by exploiting new analytical and biotechnological technologies. Molecular Biology and enzyme technology together with NMR analytics will provide disruptive innovation and lead to the development of unique new and sustainable products. Amongst the broad spectrum of potential applications for this new biomaterial, we will successfully demonstrate the cost-efficient and industrially compatible production of this new biomaterial using novel biomanufacturing technology and its benefits in reducing the environmental and economic costs of laundry. By applying analytical NMR to the novel biomaterial, its structural conformity can be verified, serving as a technical tool to potentially accelerate design and creation of cold-cleaning HPC relevant product formulations."

Polymethylmethacrylate (pMMA) is a transparent polymer, most familiar in the form of Perspex, used to make screens for phones, computers and TVs. pMMA is non-toxic, so it is used in contact lenses, medicine and dentistry. It is also used to manufacture parts for cars and aircraft, bathroom/kitchen units and fittings, and in paints and resins. Like all plastics, pMMA is made from oil-derived feedstocks. We have developed a lab-scale, bio-based route to manufacture the monomer for pMMA, methylmethacryalate (MMA). The new process uses renewable sugars instead of oil, and will generate about one fifth of the CO2 emissions compared with petrochemical MMA. To do this, we engineered bacteria to produce the enzymes needed to convert sugars to a derivative of MMA. This synthetic chemical is not usually formed by enzymes, so the artificial metabolic pathway was developed using directed evolution and synthetic biology. The product can be separated easily from the fermentation, and we developed a simple, sustainable chemical process to convert it to MMA. In this project, we will integrate synthetic biology, fermentation technology and chemical process development to take this process from lab scale experiments to a pilot scale manufacturing process.

Bacteriocins are proteinaceous toxins produced by bacteria in order to kill other, closely-related strains. Bacteriocins from bacteria which normally colonize the human body hold considerable promise to replace/augment conventional antibiotics; however, despite their potency, these compounds have not evolved to function as therapeutics. As a result, the drug development community urgently needs a generic method able to convert these promising molecules into clinically applicable agents. In this project we will take a model bacteriocin and through iterative structure-function analysis significantly enhance its performance in terms of specificity, stability and potency. This will be achieved through the development of an empirical structure-activity relationship algorithm to generate a range of derivatives exhibiting drug-like properties without compromising the potent bactericidal activity of the original compound. We will then scale-up the manufacture of selected derivatives, demonstrating our capabilities not just in discovery but also in supply. No such combined capability currently exists and this innovation will allow the project partners to gain a unique and pre-eminent position in the market for bacteriocin-derived antibiotics. Keywords: antimicrobial resistance; drug development; bacteriocins.

The advance of antimicrobial resistance (AMR) is relentless. A succession of WHO reports on AMR reveal that the problem is no longer a future or developing threat, but that it is already challenging our ability to treat common infections. To reverse this alarming trend, we need not just powerful compounds, but also powerful discovery and development paradigms. Novel antibiotics must have potent activity, but they must also serve as scaffolds for structural diversification for the sustainability of long-term functional efficacy. As with first generation antibiotics like penicillin, our goal should not just be to discover individual antibiotics but rather provide new antibiotic pipelines for a sustainable defence against AMR. This project will provide a discovery-manufacturing platform using state of the art equipment to accelerate the much-needed introduction of an exciting new class of potent antibiotics based on bacteriocins that rapidly kill bacteria, including drug-resistant Gram-negative pathogens and MRSA. The platform will deploy scalable systems for peptide antibiotic production and diversify their functional potential through rational design and discovery from novel samples, adapting their medicinal properties; thus providing a new pipeline of effective antibiotics.

A global challenge is to improve the way in which mankind improves the consumption and disposal of commodity plastics. Alternative strategies to permit production of chemically identical “like-for-like” materials from sustainable biobased feedstocks as alternatives to existing petrochemical sources is required to help met the improve consumption and disposal of plastics. This application to Innovate UK is seeking to develop highly efficient routes to prepare polymethacrylates (i.e. Perspex) from non-fossil carbon based feedstocks. The project partners will build bespoke bacteria using state of the art synthetic biology methods to enable production of methacrylate intermediates. We shall recover and test the intermediates for their practical suitability in preparing and forming the plastics that Lucite sells to its existing customers.

The proposed project is aimed towards early stage feasibility research around the biomanufacturing of commodity chemicals through the development of a novel economically attractive bioprocess that will utilise advantageous/affordable hydrocarbon feedstocks. The project will be enabled by Ingenza's unique ability to readily discover, bioengineer and exploit hydrocarbon-utilising microorganisms.

This project addresses a current severe limitation in the successful industrial use of engineered microbes, namely to rapidly achieve predictable, iterative improvements in productivity to establish competitive process economics. It combines software engineering, bioinformatics, metabolomics and high-throughput construction of recombinant bacteria and yeast, to implement a system that will accelerate the development of engineered strains for next generation biosynthesis of fuel, chemicals and polymer products, manufactured from sustainable feedstocks. The project will combine the strengths of a leading UK Industrial Biotechnology SME and a state of the art university Polyomics facility to demonstrate a step change in the UK’s capability to develop new industrial bioprocesses.

Nasogastric (NG) tube feeding is common practice in hospitalised children and neonates to facilitate nutrient intake and medication administration. However, tube misplacement is not uncommon and is a significant issue as a tube misplaced into the lungs instead of the stomach can be fatal. This has led the NHS to recently classify NG tube misplacement as a ‘never event’. Children and neonates are at increased risk of misplacement compared with adults because of their age, increased activity and non-purposeful movement of limbs or the head and neck. ). To address misplacement issues, Ingenza have devised a novel, easy to use, low cost point-of-care (PoC) test for confirmation of the safe placement of NG tubes in neonates and children. An easy and reliable PoC test will allow ongoing verification of the location of the device and its tip with accuracy. It will reduce harm occurring to children and neonate in NG tube feeding. It will reduce exposure to X-ray radiation and avoid delays in initiating and advancing enteral nutrition.

Bacillus licheniformis is a preferred host for the production of industrial enzymes, including proteases for detergent and amylases and cellulases for food and biofuels. To advance its genetics/utility our key objective is to deploy SynBio tools to improve endogenous and heterologous enzyme production economics in B. licheniformis for exploitation via leading end users. Genome delivery technologies will amplify/target genes to locations validated for high-level/predictable expression, overcoming issues associated with non-targeted integration. Nuclease-based genome editing will a) address yield- compromising aspects of host metabolism under stress conditions identified through systems biology and b) capitalize on in situ protein engineering to improve endogenous enzyme function including thermotolerance and optimal activity under operating conditions. Success in these areas will reduce the cost and improve the versatility and efficiency of industrial enzymes produced in B. licheniformis.

Ribosomally Produced Peptides (RIPPs) are widely recognised as one of the most promising classes of compounds with the potential to treat many diseases including infection, cancer & inflammation. They are of great interest to the pharma industry, but are extremely costly to produce/modify - even in milligram amounts. Through the utilisation of cutting-edge techniques in combinatorial synthetic biology, this project sets out to achieve a world first; namely, to produce bespoke libraries of Modified RIPPs (M-RIPPs) in sufficient quantities to permit drug discovery screening. The project combines the fundamental knowledge of the natural processes involved in RIPP biosynthesis of the two premier UK academic groups active in the field with the applied expertise in industrial biosynthesis of a leading UK IB company. It will deliver a versatile yet robust technology platform for the production of M-RIPPs that will be commercialised via a new UK spinout company.

Antibiotic resistant bacteria kill over 25,000 people a year in Europe and threaten a return to a time when minor infections can be fatal and routine surgery poses high risks. With development pipelines empty, there is a critical need for novel therapies to kill antibiotic resistant bacteria and serve as scaffolds for derivatisation, diversification and enhancement of efficacy, which proved successful with drugs like penicillin. This project will develop an exciting new class of antimicrobial biologics that rapidly kill bacteria, at very low doses and have great potential to prevent or treat bacterial infections including those caused by resistant bacteria. However, the development of the primary targets is hampered by their very low production in the native host and synthetic production would be prohibitively expensive. This project aims to develop efficient, adaptable and scalable microbial production systems for this novel compound class, enabling their development into a new platform of effective antibiotics.

Our pilot study (n= 23, including 15 patients on antacid medications) found this new test was 100% accurate. The results, if validated further in this proposed, thorough clinical evaluation and scientific device development programme, mean that the new test would reduce feeding incidents due to misinterpretation of pH strip and X-ray results and cut the need for chest x-rays by about a third. Wider benefits to healthcare providers and patients include 1) significant cost savings (£1 per enzymatic test versus £120 per x-ray); 2) reduced risk of misdiagnosis of misplaced NG tubes; 3) biopsychosocial improvements for patients, 4) greater confidence and reliability in nursing care and 5) improved patient care and safety. Upon validation, there would be clear potential to apply related enzymatic marker detection more broadly to detect disease, health monitoring and infection.

Synthomer and Ingenza will continue the collaboration begun in a successful TSB co-funded Feasibility Study. Synthomer have identified a market gap for a product which if made using industrial biotechnology would have improved properties and none of the drawbacks of similar materials made by existing manufacturing technologies. They anticipate that this product would be rapidly assimilated into one of their key market areas due the improved characteristics. Synthomer are a top 5 global supplier of emulsion and specialty polymer company with vast experience in this target market. Ingenza are a biotechnology enabler who develop novel bioprocesses using proprietary technologies. Ingenza will develop a bioprocess by creating a GM microorganism capable of manufacturing Synthomer's product. Following the successful completion of the programme, Synthomer and Ingenza expect to enter into a lasting collaboration to optimise a sustainable manufacturing bioprocess for this unique product.

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Awaiting Public Project Summary

Ingenza and the University of Nottingham will engineer microorganisms for the utilisation of xylose and its conversion to products of interest by fermentation. We will exemplify the approach by converting xylose to a key intermediate required by Lucite International for the manufacture of monomers using sustainable bioprocessing. Use of xylose, derived from waste ligoncellulosic biomass, allows the production of chemicals by fermentation using sustainable raw materials whihch in no way compete with sugars produced for food use.

The collaboration between Synpromics and Ingenza is focused on developing proprietary protein production systems in engineered yeast strains that improve on currently available alternatives by incorporating novel synthetic promoter constructs rationally designed to drive optimal gene expression. The enabling technology that the project aims to deliver will address significant limitations faced by a wide range of bio-manufacturers using yeast-based expression, enabling the more efficient production of protein products and intermediary production enzymes. The combination of Synpromics's and Ingenza's innovative technologies and expertise is expected to validate a platform on which to build an even broader range of solutions to yeast-based expression challenges, thereby establishing in the UK a leading capability in synthetic biology and sustainable industrial bioprocessing.

Awaiting Public Project Summary

Cyanobactins are cyclic peptides that may be very effective in combating many disease states including inflammation and infection. There is great interest from the pharma industry in their development as therapeutic agents but these compounds are extremely challenging to produce with existing methods, severely hampering their production. We aim to overcome this limitation, using combinatorial synthetic biology, to design and build the necessary complex synthesis pathways in engineered microbes for scalable production of native and derivatised patellamides. This collaboration combines an academic group with deep knowledge of patellamide biosynthesis and biology with a leading UK based IB company with expertise and facilities necessary to expedite the required synthetic biology approach. The project will deliver novel and improved products and processes to test native and novel cyclic peptides in the treatment of disease.

Success of this project will overcome a persistent and severe limitation of the critical enabling technology required for the successful industrial use of engineered microbes, namely to adapt cloned gene codon distribution optimally to produce heterologous proteins efficiently and in an active form in microbes suitable for industrial scale-up. The project combines a leading UK industrial biotechnology SME and a world class academic centre to demonstrate a critical advance in the UK’s capability to develop novel industrial bioprocesses for the manufacture of high value building blocks for high value chemicals. The project will de-risk new processes and developing projects through to pilot scale and builds upon a successful TSB feasibility study. It will overcome normally slow, empirical and iterative methods to greatly accelerate development of engineered industrial strains.

This project will develop new bioprocesses to convert lignin, one of the world’s largest natural by-products of lignocellulosic biomass and paper and pulp processing, to a sustainable source of high value chemical building blocks. It will also demonstrate feasibility to replace unsustainable petrochemical derived raw materials, currently used in the manufacture of chemicals, plastics and packaging. Proven, manipulable strains of industrial yeast will be engineered using methods of, combinatorial genetics, bioinformatics and synthetic biology to permit many hundreds of specific enzyme combinations to be tested for optimal lignin degradation. The project will demonstrate the potential for synthetic biology to construct and optimise industrial microbes suitable for economical, enzymatic degradation of lignin with characterisation of the resulting products as potential new raw materials for the chemical industries.

Ingenza, Lucite and the University of Cambridge will apply innovative genome-scale flux balance analysis to rationally redesign the biochemistry of this organism to synthesise a high value polymer intermediate. Lucite, a UK based global leader in acrylic polymer manufacture will provide expert downstream chemistry, engineering and the route to market for the resulting bioprocess, replacing petrochemical derived feedstocks. Model-driven synthetic biology will overcome limitations of more random, iterative approaches, providing a new manufacturing platform, in an industrially compatible timeframe. Combinatorial genetics will construct the engineered microbes and plant design modelling by the end user will assess manufacturing options. Thus, the project combines bioinformatics, molecular biology and engineering to produce a suitable, safe and sustainable bioroute to one of the world’s most important and valuable industrial products.

Synthomer have identified a market gap for a product which if made using industrial biotechnology would have improved properties and none of the drawbacks of similar materials made by existing manufacturing technologies. They anticipate that this product would be rapidly assimilated into one of their key market areas and leverage market acceptance due the the improved characteristics. Synthomer are a top 5 global supplier of emulsion and specialty polymer company with vast experience in this target market. Ingenza are a biotechnology enabler who develop novel bioprocesses using proprietary technologies. Ingenza will demonstrate feasibility for a bioprocess by creating a genetically modified microorganism capable of being used in Synthomer's product. Following the successful completion of the Feasibility Study, Synthomer and Ingenza expect to enter into a lasting collaboration to optimise a sustainable manufacturing bioprocess to replace conventional oil based synthesis.

Awaiting Public Summary

This project aims to provide a new set of enabling technologies which will create a step change in the speed and efficiency with which engineered microbes can be constructed for industrial application. This improvement will be achieved by combining novel methods to recombine genes within the genome of industrial organisms with advanced metabolomics techniques and direct screening methods to identify strains with improved process efficiency. The project output will provide methods to overcome the normally time-consuming and laborious empirical process of iterative strain improvement. The initial application is to rapidly improve yeast strains used for bioethanol production but the suite of enabling tools being employed would be capable of accelerating the development of microbes for virtually any industrial application.

This project addresses a severe limitation of the critical enabling technology required for the successful industrial use of engineered microbes, namely to rapidly achieve efficient production of proteins from heterologous DNA, either as end products in themselves or as enzymes whose concerted action produces other high value products. The project follows a highly successful TSB Feasibility study to evaluate the use of innovative enabling technology that combines bioinformatics and genetic recombination, to accelerate the development of engineered strains for applications that include very high value biologics, food, feed and fuel products, all manufactured from sustainable feedstocks. The project will combine the strengths of two UK SMEs, a leading proponent of industrial microbes and a world class culture collection centre to demonstrate a step change in the UK’s capability to develop new industrial bioprocesses.

Awaiting Public Summary

The concept of ‘green chemistry’ to promote chemical technologies that reduce the generation of hazardous substances is increasingly relevant within the UK chemical industry. The current trend is towards the bio-based production of chemicals and the potential of industrial biotechnology to provide the process tools to achieve this. This project will integrate all phases of bioprocess development from catalyst production, to process design, through to highly efficient small footprint manufacture of high value products with a focus on the application of high pressure systems in biotechnology to produce high value chiral intermediates. BioPress will demonstrate the flexibility of a high pressure reactor on a lab scale and on a pilot production scale. The advantages of a pressurised system are seen with the increased efficiency of gas transfer to the reaction medium. Adoption of efficient bio-processes and improved process design will be key to the future success of these sectors. This project brings together three UK SMEs that are world leaders in biocatalysis, process design and small footprint reactor technologies to deliver significantly improved economics in existing and new chemical manufacturing processes. Speciality and fine chemicals sectors are of major significance, providing ‘high-value, knowledge-intensive goods'. The consortium will focus on the introduction of high pressure biotransformations enabling the production of high quality product in a reduced time frame. The application of integrated process and reactor design will reduce the timescale and the technical risks currently experienced in adapting existing bioprocesses to new targets and in transferring laboratory or pilot scale reactions to full scale manufacturing processes. BioPress will prove the advantages of the innovative reactor design and detail the process improvements for the industry sectors.

In this project Ingenza, a World-leading Synthetic Biology company, Ark Genomics, a World-leading laboratory focused on the genome sequencing and the Rowett Institute of Nutrition and Health will collaborate to identify new high-perfomance industrial biocatalysts from the rumen of livestock. Metagenomic data from diverse rumen derived microbes is an unprecedented source of enzymes for industrial biotechnology. The consortium believes that the enzyme activities will be applied in novel bioprocess applications and to improve existing bioprocesses for the sustainable production of chemicals and biofuels. The project will also further the understanding of how the microbiology of the rumen contributes to overall animal health.

In this project Ingenza, a World-leading Synthetic Biology company, and Lucite International, the global leader in Acrylics, will develop processes for the manufacture of monomer intermediates built around an Industrial Biotechnology platform. Ingenza will use it's state-of-the-art portfolio of Synthetic Biology tools to produce microbes capable of producing the chemicals by fermentation. Lucite will focus on the conversion of the intermediates to monomers and polymers for the manufacture of acrylate polymers. The project will further develop Ingenza's Synthetic Biology toolkit and allow Lucite to replace current petrochemical routes to monomers with new sustainable manufacturing processes.

In this project Ingenza, a World-leading Synthetic Biology company, and Ark Genomics, a World-leading laboratory focused on the genome sequencing will collaborate to identify and analyse the genomes of genetically modified yeast used for the production of biofuels. The rational interpretation of the resulting genotypic data will greatly accelerate Ingenza's strain improvement programme focused on the development of more efficient bioprocesses for the production of biofuels.

Awaiting Public Summary

The public description for this project has been requested but has not yet been received.

The public description for this project has been requested but has not yet been received.

Three UK technology companies, C-Tech Innovation, Ingenza and AM Technology have collaborated in the BIOCHEMIST project to develop new flow process techniques for bio manufacturing. The project integrated all aspects of bioprocess development from enzyme discovery and catalyst engineering, to process design, through to small footprint manufacturing of high value products. The CofloreTM Agitated Cell Reactor (ACR) is a dynamically mixed plug flow reactor and Coflore Agitated Tube Reactor (ATR) - an industrial tube flow reactor both developed by AMTech have demonstrated superior mixing and process control in bioprocess development starting from simple lab scale batch processes. The BIOCHEMIST project successfully implemented pug flow principles to chiral chemical manufacturing through benchtop plug flow reactors (ACRs); and on to the multi-litre production scale agitated tube reactor (ATR). A synthetic oxidation reaction developed by Ingenza for the production of chiral amino acid catalysed by a series of novel d-amino acid oxidases (DAAO) has been developed from lab to pilot scale process by C-Tech Innovation under batch and continuous conditions, and illustrates how application of the ACR and ATR reactors can facilitate process development by improved process control; ease of scale up; minimizing of interruptions in production; reducing reactor size; and the efficient and economic use of biocatalysts

Awaiting Public Summary

Awaiting Public Summary

Awaiting Public Summary