Mycoplasmas are the smallest cell wall less, free-living microorganisms. The lack of a cell wall makes them resistant to many of the common antibiotics. Every year, infections caused by Mycoplasmas in poultry, cows, and pigs, result in multimillion euros losses in USA and Europe. Currently, there are vaccines against M hyopneumoniae in pigs and M gallisepticum and M synoviae in poultry. However, there is no vaccination against many Mycoplasma species infecting pets, humans and farm animals (ie M bovis cow infection). Mycoplasma species in many cases are difficult to grown in axenic culture and those that grow need a complex media with animal serum. In large scale production of Mycoplasma species for vaccination aside from the high cost of animal serum, more important is the high irreproducibility in the production process and the possible contamination with animal viruses. All this together highlights what European industry needs:i) a defined cheap reproducible medium that is animal serum free and ii) an universal Mycoplasma chassis that could be used in a pipeline to vaccinate against Mycoplasma species, as well as any pathogen. M pneumoniae is an ideal starting point for designing such a vaccine chassis. It has a small genome (860 kb) and it is probably the organism with the most comprehensive systems biology data acquired so far. By genome comparison, metabolic modeling and rationally engineering its genome, we will create a vaccine chassis that will be introduced into an industrial pipeline. The process will be guided by the second world largest industry on animal vaccination (MSD), as well as a SME specialized on peptide display and screening. This will ensure the exploitation and commercialization of our work contributing to maintain Europe privileged position in this field. Our ultimate goal is to meet the needs of the livestock industry,taking care of ethical issues, foreseeable risks, and prepare effective dissemination and training material for the public.

Industrial Biotechnology (IB) is a Key Enabling Technology for the circular bio-economy, industrial renewal and European manufacturing autonomy. Its development forms a vital part of EU’s strategy to become climate neutral in 2050. For IB to become a major manufacturing technology, it must widen its use of advanced digital technologies. These will improve R&D efficiency, reducing time-to-market and costs. Moreover, for manufacturing, advanced digital technologies will drive distributed, autonomous and highly adaptable production systems. To support digitalization of IB, BIOINDUSTRY 4.0 will create new services delivered by European research infrastructures (RI). These services will address several challenges, focusing on the acceleration of bio-process development pipelines. Drawing on the complementary skills of its consortium, BIOINDUSTRY 4.0 will develop data-driven approaches, exploiting AI to empower novel decision support systems and digital twins, the latter being to better design bio-processes and enable their real-time online control. To complete these services, BIOINDUSTRY 4.0 will also develop data and metadata standards to generate high quality, interoperable multi-scale bio-process data, the technical basis for trusted data networks and process analytical devices to provide real-time online monitoring of bio-processes. Once deployed, these RI services will provide Users with access to cutting-edge technologies that can be used singly or in an integrated way, covering whole R&D pipelines. Integrated services will be delivered by a distributed RI, conferring Europe with a unique R&D test-bed for bio-process development and a competitive advantage with respect to global competition. To succeed, BIOINDUSTRY 4.0 brings together 6 EU RIs, 1 global company, 2 innovative EU SMEs and several research teams around an ambitious 4-year workplan that will be implemented in consultation with IB stakeholders, using a co-design strategy to specify goals.

This Project is about bringing a suite of chemical reactions (and its related non-biological compounds and elements) to the biological fold (i.e. their 'biologization') by going beyond the Central Dogma of Molecular Biology (DNA→ RNA→ proteins→ metabolism) through both tuning and overcoming the uni-directionality of the information flow. To reverse-engineer reactions into a biological code, the utility function of the chemical process of interest will be progressively coupled to the fitness function of a live carrier (e.g. an engineered, synthetic or cyborg-ized bacterial chassis), the intermediate steps being supported by automated chemo-robots. The new-to-nature reactions (NTN) pursued within the MADONNA lifetime as case studies will include CO2 capture and recruitment of elemental silicon to become part of essential organo-Si metabolites. Along with the development of the new reactions, the research agenda of the Project will also include the [i] modelling and prediction on the impact of the new biotransformations on the overall functioning of the Biosphere once/if adopted at a large scale by the industrial sector and [ii] design of environmental simulators for evaluating the performance and evolution of the new biological reactions under given physico-chemical settings. With such approaches, MADONNA aims to fill many of the gaps between the 3 types of global-scale processing of chemical elements operating in our planet: Geochemical, Biological and Industrial. The scale of applications of the foundational technologies developed herein (which spin themselves much beyond CO2 and silicon) is unprecedented and a large number of societal ramifications including ethical, security, safety, economic, governance and public perceptions aspects at stake will be included. If successful, MADONNA will enable an entirely new type of sustainable industry in which many types of waste become assets instead of liabilities.