The agri-food system, producing 23% of UK emissions, must play a key role in the UK's transition to net zero by 2050, and through leadership in innovation can support change globally. Our Network+ will build on existing and new partnerships across research and stakeholder communities to develop a shared agenda, robust research plans, and scope out future research and innovation. The Network will design and deliver high-reward feasibility projects to help catalyse rapid system transformation to ensure the agri-food system is sustainable and supports the UK's net zero goal, while enhancing biodiversity, maintaining ecosystem services, fostering livelihoods and supporting healthy consumption, and minimising the offshoring of environmental impacts overseas through trade. The radical scale of the net zero challenge requires an equally bold and ambitious approach to research and innovation, not least because of the agri-food and land system's unique potential as a carbon sink. Our title, Plausible Pathways, Practical and Open Science, recognises the agri-food system as a contested area in which a range of pathways are plausible. Success requires that new relationships between natural and social science, stakeholders including industry, government and citizens, be forged in which distributed expertise is actively harnessed to support sectoral transformation. We will use our breadth of expertise from basic research to application, policy and engagement to co-produce a trusted, well-evidenced, and practical set of routes, robust to changing future market, policy and social drivers, to evolve the agri-food system towards net zero and sustainability. Marshalling our many existing stakeholder links, we will review and evaluate current options and use Network funding to catalyse new partnerships through retreats, crucibles, workshops, online digital networking and scoping studies to develop system approaches to transformation, reframe the research agenda and undertake novel research projects. We will co-design productive and creative spaces that enable the research community to engage with a wide range of stakeholders and thought leaders through the following framework: 7 Co-Is who govern the Network but are not themselves eligible for funding; 9 Year-1 Champions (with new appointments after Year 1) dynamically forging new connections across research communities; 11 Advisory Board members tasked with challenging business-as-usual thinking; and regular liaison with other stakeholders.

This collaborative proposal aims to characterise branching patterns in filamentous fungi in order to provide insights into gene network function and regulation. This will not only lead to fundamental insights into the molecular mechanism of hyphal branching across many species of filamentous fungi, but will help our industrial partners improve process efficiencies, ensuring that Quorn continues to be one of the most sustainable, non-plant-based, meat alternatives on the market. In the 1950's, prior to the 'green revolution' there was serious concern about the availability of sufficient protein to feed a growing global population. Rank Hovis McDougal (RHM) began a process of searching for a single celled protein source that could be fermented using wheat starch (or derived glucose monomers). This led to the discovery of a Fusarium species, that has the correct growth properties that enabled onward processing. Later classified as Fusarium venenatum (Fv), a sister species to the wheat pathogen Fusarium graminearum, this filamentous fungus grew in a manner that had good organoleptic properties following mixture with egg albumen, forming, cooking and controlled freezing, which cause mycoprotein filaments to align as a fibre-gel composite conferring a meat-like texture . During the production of mycoprotein, spontaneous variants arise in the fermentation which branch more quickly and eventually rise to high levels in the fermentation process. These are undesirable from a food texture perspective as they lead to a crumbly, rather than a meaty texture and therefore fermentations must be terminated early, leading to less efficient production that would be possible without these colonial variants (also known as c-variants). Our previous work has sequenced 'c-variant' genomes from 19 independent fermentations and revealed a common set of genes that are mutated across c-variant isolates in different combinations. We now wish to verify which of these genes (and in what combination) are responsible for the c-variant phenotype. This will help us to understand which genes are responsible for controlling hyphal growth and branching, currently an 'unknown' in most filamentous fungi. We will validate our hypotheses about which variants are important by using a combination of machine-learning approaches which will allow us to effectively group c-variant isolates to aid with gene identification. We will look at gene expression perturbations across each mutant isolate, which in combination with 'active learning' approaches, allow us to identify the regulatory order of the gene expression network. We will, in collaboration with Marlow Foods then look to understand the order of mutational events within the fermentation process and with a combination of ultra-deep population-level genome sequencing and digital droplet PCR techniques track the dynamics of individual mutations within the commercial fermentation process. We will also ask if this mutational trajectory is dependent upon the strain which is chosen for fermentation, as it may be that the current production strain is more susceptible to hyper-branching variants than other strains. Finally, we will link together morphological growth models with gene expression networks to model the effects of different gene perturbations on the growth and branching process. This, along with other analyses will allow us to look at the robustness of the gene regulatory network and identify whether there are opportunities to improve the robustness of strains through enhanced mechanistic insight into how the hyphal growth and branching system functions and is regulated. Taken together this work will allow the rational design of new strains of mycoprotein, enhance production efficiency and ensure that scalable alternatives to meat can be sustainably produced.

Industrial Biotechnology (IB) is entering a golden age of opportunity. Technological and scientific advances in biotechnology have revolutionised our ability to synthesise molecules of choice, giving access to novel chemistries that enable tuneable selectivity and the use of benign reaction conditions. These developments can now be coupled to advances in the industrialisation of biology to generate innovative manufacturing routes, supported by high throughput and real-time analytics, process automation, artificial intelligence and data-driven science. The current excess energy demands of manufacturing and its use of expensive and resource intensive materials can no longer be tolerated. Impacts on climate change (carbon emissions), societal health (toxic waste streams, pollution) and the environment (depletion of precious resources, waste accumulation) are well documented and unsustainable. What is clear is that a petrochemical-dependent economy cannot support the rate at which we consume goods and the demand we place on cheap and easily accessible materials. The emergent bioeconomy, which fosters resource efficiency and reduced reliance on fossil resources, promises to free society from many of the shortcomings of current manufacturing practices. By harnessing the power of biology through innovative IB, the FBRH will support the development of safer, cleaner and greener manufacturing supply chains. This is at the core of the UKs Clean Growth strategy. The EPSRC Future Biomanufacturing Research Hub (FBRH) will deliver biomanufacturing processes to support the rapid emergence of the bioeconomy and to place the UK at the forefront of global economic Clean Growth in key manufacturing sectors - pharmaceuticals; value-added chemicals; engineering materials. The FBRH will be a biomanufacturing accelerator, coordinating UK academic, HVM catapult, and industrial capabilities to enable the complete biomanufacturing innovation pipeline to deliver economic, robust and scalable bioprocesses to meet societal and commercial demand. The FBRH has developed a clear strategy to achieve this vision. This strategy addresses the need to change the economic reality of biomanufacturing by addressing the entire manufacturing lifecycle, by considering aspects such as scale-up, process intensification, continuous manufacturing, integrated and whole-process modelling. The FBRH will address the urgent need to quickly deliver new biocatalysts, robust industrial hosts and novel production technologies that will enable rapid transition from proof-of-concept to manufacturing at scale. The emphasis is on predictable deployment of sustainable and innovative biomanufacturing technologies through integrated technology development at all scales of production, harnessing UK-wide world-leading research expertise and frontier science and technology, including data-driven AI approaches, automation and new technologies emerging from the 'engineering of biology'. The FBRH will have its Hub at the Manchester Institute of Biotechnology at The University of Manchester, with Spokes at the Innovation and Knowledge Centre for Synthetic Biology (Imperial College London), Advanced Centre for Biochemical Engineering (University College London), the Bioprocess, Environmental and Chemical Technologies Group (Nottingham University), the UK Catalysis Hub (Harwell), the Industrial Biotechnology Innovation Centre (Glasgow) and the Centre for Process Innovation (Wilton). This collaborative approach of linking the UK's leading IB centres that hold complementary expertise together with industry will establish an internationally unique asset for UK manufacturing.

As prosperity rises, demand for meat increases as it is a rich source of protein. This in turn places demand on water resources, changes land use (in a manner highly dependent upon how the animal is fed) and leads to an increase in anthropogenic GHG emissions. This has been determined to be unsustainable by a number of international bodies, with some estimates predicting a 70% rise from current levels of 11% of total GHG emissions by 2050. However, demand for protein can also be met by crop-based sources (e.g. soy and pulses) and by mycoprotein, produced by fermentation of crop-derived glucose into biomass, which is harvested and processed into high quality protein. Mycoprotein remains a relatively under-exploited resource worldwide but offers great promise for year-round production of high quality protein, a vital requirement for future food security and human nutrition. The most significant challenge to production is the reliance on a single carbon source, a wheat-derived glucose, which requires special processing before it is suitable for use. Our recent work has revealed that while the fungus used to produce mycoprotein is grown on this glucose substrate, production of a number of essential vitamins is inhibited. Our recent work has revealed that expression of vitamins in some other carbon sources, for example beet derived sucrose syrup is observed. In some, but not all cases, this is coupled to an increase in other deleterious secondary metabolites. This leads to the question, how is the fungus regulating secondary metabolism in relation to carbon source? To expand both the nutritional value of mycoprotein and the range of carbon sources that can be utilised (enabling production to move to other regions of the world) we will use the latest DNA sequencing techniques to reveal the structure of the genome of Fusarium venenatum and study the regions of the genome that contain secondary metabolite genes. From work carried out in other related fungi it is known that control of secondary metabolism (SM) is regulated by the position of SM cluster in the genome, and by specific regulatory factors. Utilising the latest sequencing techniques will allow us to positionally resolve SM location and determine the underlying mechanisms regulating responses to different carbon sources. Through a series of controlled batch and continuous culture experiments we will develop techniques to selectively induce vitamin biosynthesis across a range of carbon sources, without inducing the expression of deleterious SM genes, providing both an understanding of the control of SM and an enhanced product for future product development. Building on our existing work we will expand the toolbox of molecular techniques in order to edit the genome of F. venenatum to remove deleterious secondary metabolite gene clusters and their regulatory factors which are induced in response to different carbon sources. As a result of this work, mycoprotein will be able to be produced using a larger range of carbon sources drawing upon a wider range of UK agricultural sources (maize, barley, rice) and even shift to sucrose-based production of mycoprotein (a carbon source that has currently been completely inaccessible), utilising UK sources of sucrose such as sugar beet. Furthermore, the ability to enhance the complement of micronutrients in mycoprotein will broaden its utility as an important component of global diets and offers a more sustainable and flexible alternative to meat.