Public Funding for Herlab Ltd

Synthetic biology has a potential to enable cheaper, cleaner, more economically and environmentally sustainable biomolecule production. Animal-free rennet (for cheese production), insulin (for medical purposes), and leghemoglobin (for alternative meat production) are all produced using a process called precision fermentation -- where a microorganism is modified into a mini-factory of a desired molecule. However, despite massive advances in precision fermentation, it remains difficult to achieve sufficient production of some proteins, resulting in high production costs and limiting their beneficial impact for businesses. Precision fermentation has a number of techniques to improve production, but these techniques are labour-intensive and limited by our current understanding of regulatory sequence coding principles. In this project, we will evaluate the potential of _in silico_ optimization for protein production. We will validate machine-guided sequence optimization for the industrial production of a high-value protein. Like many recombinant proteins, its production costs are driven by a complicated production process in prokaryotes and costly purification. Yeast production systems have been shown to be more advantageous for such protein production but their titers are not yet on par with _E. coli_. The purpose of this project is to improve the cost efficiency of these yeasts for high-value protein production. More broadly, our project will provide a pathway to the development of economically and environmentally sustainable production chassis for protein ingredients, critical to food, cosmetics, and pharmaceuticals markets. By using precision fermentation to create these ingredients, we can reduce the carbon footprint of the production process, as well as address issues of food security and public health. Moreover, we hope that our pipeline will open up novel avenues for precision fermentation of other high-value proteins that currently have no means of scaled manufacturing. Our proposal seeks to overcome the limitations of current practices and leverage evolving technologies to accelerate the development of new expression systems for biomanufacturing. We aim to create an _in silico_ optimization platform that can drive innovation in this field and solve major production bottlenecks, significantly contributing to the growth of the biotechnology sector in the UK.

The demand for dairy products is growing globally due to the rising income, increasing population, and dietary changes. Concerningly, dairy production is one of the biggest methane emitters in the world. Animal-free alternatives for dairy products have the potential to reduce pollution by offering sustainable production practices. However, while plant-based alternatives for milk have nearly reached price, taste, and convenience parity to animal-derived milk, plant-based cheese still fails to offer an adequate consumer experience. In the last 10 years, the potential use of precision fermentation -- a process where genetically modified microorganisms are used as cell factories to produce desired biomolecules, such as pharmaceuticals and biofuels -- has been investigated for food protein production. While in principle precision fermentation offers a sustainable and ethical way of producing food proteins, to date no major alternative protein company has been able to offer affordable and scalable solutions to casein -- the main cheese protein -- production. We argue that the lack of progress is mainly due to the attempts to genetically engineer conventional industrial microorganisms such as _E. coli_ and _S. cerevisiae_ that require multiple modifications to utilise cheap food sources, withstand environmental pressures in bioreactors, and produce complex proteins. Indeed, since 2014 the alternative protein sector already saw great improvements after expanding optimisation efforts to less popular but scientifically well-established species of _P. pastoris_ and _T. reesei_. We propose that even larger gains can be achieved by adopting unconventional yeast species that might be naturally more suitable for food production but currently lack the necessary genetic engineering tools. We aim to develop the next-generation microbial factories using unconventional microbial species. Our methodology will be validated in pilot-scale bioreactors evaluating the novel strains for the industrial production of casein proteins. This proof-of-principle project will serve the whole precision fermentation sector by massively expanding the choice of protein expression systems, tailored for industrial level scalability.

Our food system is facing challenges that require innovative solutions. One emerging solution is alternative proteins, which have the potential to reduce the environmental, ethical, and health impacts of animal agriculture. However, to be a viable alternative, these proteins must achieve taste and price parity with conventional animal-based products. Our innovative yeast technology is designed to meet this challenge. We're using cutting-edge synthetic biology and machine learning tools to identify and develop next-generation yeast strains that are highly efficient and scalable for industrial-scale protein production. Our project focuses on demonstrating the viability of this approach by focusing on two of the most promising species identified by us in the lead-up to this project. Our goal is to use them to produce two biomolecules of economical and environmental significance in food production. If successful, this proof of concept will validate the promise of our yeast screening platform, unlocking the possibility for developing multiple next-generation yeast strains for a more sustainable and more affordable food, cosmetics, and even pharmaceutical ingredient production. Moreover, our approach carries broader implications for the biotechnology industry, as our unique yeast screening platform bears a transformative value for a wide range of active applications. Our innovative approach to sustainable protein production will have a significant positive impact on the environment, public health, and the economy. By reducing dependence on animal agriculture and petroleum-derived ingredients, we can create more sustainable food and health systems that benefit our society.