Le Laboratoire de Biotechnologie et Bioprocédé, les sociétés Lesaffre, ARD, Safisis et Maguin proposent un projet de conversion biologique des hydrolysats lignocellulosiques de paille de blé en éthanol à usage biocarburant. Il s’agit de sélectionner un ou des micro-organismes capables de fermenter les sucres C6 et C5 issus du traitement de la paille de blé, de le mettre en oeuvre dans une configuration de bioprocédé associant saccharification, fermentation et valorisation des produits et co-produits dans des conditions optimales de productivité, titre et rendements. Une attention particulière sera accordée à l’influence des inhibiteurs HMF et furfural sur la conversion microbienne. Nous proposons la démonstration à l’échelle du laboratoire, à l’échelle pilote pré-industriel et la validation au niveau de l’application des procédés industriels destinés à la production d’éthanol. Dans une action fédérative, cette démonstration s’étend de la préparation du substrat selon les recommandations des projets retenus dans les phases amont du programme, la fermentation et la distillation. L’analyse technico-économique sera confiée à Organibio. Il mobilise des chercheurs et des industriels majeurs du domaine. D’une durée de trois ans, ce projet constitue une étape indispensable au lancement d’une véritable filière industrielle compétitive de production nationale de biocarburants, tout en contribuant au respect des engagements français dans le domaine du Développement durable.

Because of the finite nature of fossil fuel resources and the imminent climate change caused by their intensive use, the demand for renewable materials and bio-based chemicals for industrial applications, as well as for renewable energy, will steadily increase. Due to the inherent techno-economic challenges of biochemical compound commercialization, BioC4 will focus on developing technologies around ‘bio-isobutanol’, a powerful compound platform from which multiple products with high market potential can be launched. Isobutanol can be converted synthetically to many valuable building-block chemicals or directly used in fuel with multiple advantages. it can be converted easily to isobutylene or can replace n-butanol as industrial solvent. BioC4 is a collaborative project between Lesaffre, INRA, GlobalYeast and Frankfurt and Hohenheim Universities. These private and public European partners will develop a production process with high economic impact in the area of food and non-food biomass production and transformation systems. The aim is to develop an industrial isobutanol production process. For that purpose, a strong isobutanol-producing yeast strain will be developed during the 3 years of the project. It will have the ability to ferment both hexose and pentose sugars under the harsh conditions present in lignocellulose hydrolysates. In parallel, promising miscanthus genotypes with high saccharification potential will be identified and the most interesting ones will be analyzed once the process will be developed. Furthermore, a detailed concept for treatment and utilization of the fermentation residues (biogas) will be generated and evaluated. The environmental and agricultural impact of the newly developed value chain will be estimated and concepts for optimized integration of miscanthus production in cropping systems will be developed. These concepts will aim to maximize the environmental and agronomic benefits of the crop miscanthus. The environmental impact will be assessed by greenhouse gas emission and energy balance calculation. The results of the study will be used to identify weak-points and optimization potential of the developed value chain. BioC4 will develop a transportation fuel with low greenhouse gas emission, without compatibility issue with existing engines. In addition, since isobutanol can be transformed in isobutene by a single step of dehydration, it can serve as a building block for bio-based raw materials. BioC4 will also provide valuable information on miscanthus cultivation in order to promote this crop for biobased molecule production. However, the bioengineered tool developed during the project can consume glucose and xylose, so it will also be available and valid for the use of agricultural waste products and create a new output for their valorization. The BioC4 project will permit a better use of biomass waste from any plant source, and thus will help to decrease the environmental footprint of agriculture by reducing greenhouse gas emissions.

Polymyxin E, also known as colistin, was used initially in humans for treatment of infections caused by Gram negative bacteria. Because of its nephrotoxicity, colistin was withdrawn from therapeutic use in humans. Nevertheless, with increasing microbial resistance to current antibiotics and the lack of new drug candidates in the pipeline, colistin has now been reintroduced into human therapy as a drug of last resort to treat multi-drug resistant Gram negative bacteria. Importantly, colistin is also used in pig farming and in overall veterinary medicine to control Escherichia coli post-weaning diarrhea, which could lead to major economic losses. Colistin is clearly of major importance for human and animal welfare and its utilization requires a better management in order to avoid selection of resistant strains. The main purpose of the Sincolistin project is to reduce drastically the amount of colistin used in pig farming through the development of novel, sustainable and innovative antibiotic products based on increasing the potency of colistin by addition of bacteriocins. Indeed, recent data from the coordinator's group have shown that colistin and bacteriocins, such as nisin and pediocin PA-1, can act synergistically against E. coli and other Gram negative bacteria. Taking advantage of this finding, formulations based on the use of colistin and bacteriocins will be developed and incorporated into chitosan nanoparticles (50-100 nm) and microspheres (5-20 µm), which will survive the harsh gastrointestinal environment and then be delivered on the appropriate infection site. Bacteriocins are safe and natural antimicrobials. They are heat stable and insensitive to pH variations, though liable to hydrolysis by proteases. Bacteriocins foreseen to be used in the Sincolistin project are pentocin LB3F2, pentocin LB2F2, bavaricin LB1F2, bavaricin LB14F1 and bavaricin LB15F1, recently isolated from lactic acid bacteria and characterized for their E. coli inhibitory activity. These bacteriocins will be assessed against a set of fully characterized colistin-susceptible and colistin-resistant E. coli isolates of swine origin obtained from the RESAPATH network, which is headed by ANSES. The bacteriocin with the higher anti-E. coli activity, designated bacteriocin X, will be characterized for its: a) Mode of action against E. coli, in order to determine the mechanism that provokes cell death. b) Ability to generate resistant mutants (frequencies of mutation vs. colistin) c) Mechanism of synergy with colistin d) Cytoxicity to porcine and human cells Bacteriocin X will be produced at larger scale after optimizing the growth conditions and determining the best parameters of production. The release and bio-accessibility of the different formulations (nanoparticles and microspheres) developed within the framework of this project will be studied in the TIM in vitro model of upper gastrointestinal tract of pig. Further, the impact of these formulations on the pig gut microbiota and the survival of colistin-susceptible and colistin-resistant E. coli isolates from swine origin will be determined in the ARCOL in vitro model of pig colon thereby establishing whether the formulations destabilize the microbiota to a lesser extent than colistin alone. Finally, the best formulation will be tested in vivo under controlled conditions in pigs, inoculated with colistin-resistant E. coli, to validate the concept and strategies developed within the framework of the Sincolistin project.

The BIOSKOH project will pave the way for a Second Generation European Circular Bioeconomy by showcasing how a number Innovation Stepping Stones can realise a breakthrough in techno-economic viability of lignocellulosic biorefineries. It will do so through a two stage investment process and development path to realise the largest (110 kton) second generation (2G) biorefinery in Europe. It starts from a brownfield industrial site in the eastern part of the Slovak Republic to realise the 1st stage Flagship plant to produce 55 kton of cellulosic ethanol per year for EU bio-fuel mandates. Partners include the full value chain starting from land owners and feedstock producers, supply chain experts and an agronomical research partner to set-up a new biomass value chain exploiting large amounts of currently unused crop residues (kton/year), and developing newly grown dedicated crops on marginal land (total circa 320 kton/year), as such revitalising the regional economy. Technology providers (Biochemtex, Novozymes and Lesaffre) developed, tested and demonstrated in the only available semi-industrial scale 2G biorefinery research plant, an innovative integrated pre-treatment, hydrolyses and fermentation package, with higher yield and lower CAPEX which will now be upscaled to the 1st of a kind commercial scale Flagship, to be built by Energochemica. Aim is to showcase techno-economic viability based on a sound business plan and 4 stepping stones (yield, biomass cost, brownfield and industrial symbiosis). Dedicated innovation actions by expert partners include assessing increased cascading potential through lignin valorisation and 2G bio-chemicals, LCA, Socio-economic impact analyses, business plan for a 2nd investment round, exploitation, dissemination and replication actions to various bio-economy clusters in Europe, thus giving both a short term and a long term contribution to the European Industrial Renaissance and bio-economy.