Today, the increase of the atmospheric CO2 originates from the utilisation of carbon fossil in our daily life. In addition to the development of alternative energy sources (solar, wind, nuclear), plant biomass is one of the main options to replace fuel for transportation sector. Thus, plant biomass is projected to play an important role in this European bioeconomy strategy. The second-generation biofuels relies on a cheap and abundant non-food material: the lignocellulose (LC). LC consists of a complex network of cellulose, hemicelluloses, lignin and proteins that cross-link with each other and is highly recalcitrant to chemical or biological degradation. However, this chemical complexity offers a vast potential in the development of biorefinery for renewable and sustainable molecules and materials for our daily lives. In Nature, lignocellulolytic microorganisms are able to metabolize and recycle plant-derived organic carbon. They achieve this by using complex arsenals of cell wall-degrading enzymes. Most of these enzymes display a modular architecture, composed of catalytic and non-catalytic modules. Some anaerobic bacterium produce a self-assembling multienzymatic complex anchored to the outer membrane that couple enzymes with complementary activities. Previous work has evidenced that spatial proximity is a key to the remarkable efficiency of the cellulosome but it is difficult to evaluate the effect of the distance and active site orientation on enzymatic synergism mainly because of the high flexibility of the cellulosome. Thus, controlling such spatial organization is of high importance to master enzymatic synergism and increase the efficiency yield of PCW deconstruction. To reach this goal, an original approach is required. CONCERTO propose to use the BioMolecular Welding tool, composed of two small proteins Jo and In that are able to spontaneously create an intramolecular isopeptidic bond. Once linked to each other, Jo-In is a rigid complex of around 6 nm wide, displaying available N- and C-terminus for fusion. Furthermore, the anti-parallel organization of Jo-In offers the ability to create chimeras and modulate the relative spatial organization of linked protein domains. However this technology is limited because there is only one pair of Jo-In, and no natural complementary pair exists. This limitation prevents from the development of more complex assemblies that are required to degrade LC. Therefore, in CONCERTO, we propose to tackle this limitation by developing new pair of Jo and In in order to create larger organization of multi-modular enzymes. Thanks to new pairs of Jo and In, original enzymatic complexes will be designed in CONCERTO and will be deeply investigating, on one hand by solving the structure of theses complexes in solution using SAXS analysis and on another hand by carefully characterising the product profile generated by such enzymatic complexes thanks to the development of an analytical strategy that does not exists today. We hypothesize that various spatial organization will alter the product profile of the hydrolysis of complex plant cell wall substrates, helping us to understand the catalytic activity/spatial organization/product profile relationship within nanomachine and paved the way toward the control of biomass deconstruction.

In all modern agricultural crops, the improvement of vegetable production of economic interest is based mainly on the control of pests and vectors of diseases. Pesticides application involves the use of chemicals with insecticidal, fungicidal, bactericidal properties. However, the expansion of their field application has created serious problems impacting human health and animals. In addition, excessive use of pesticides can leach into soils and water leading to land as well as groundwater pollution and wider biodiversity losses. Some of these products currently used to control pests are extremely toxic in inducing serious human diseases, such as cancer and immune and nervous system disorders. Current use of plant protection products in conventional and/or organic farming systems should be reconsidered taking in account their side effect on environment, non-target organisms, animal and human health. Such potential risk can be reduced through development, testing and demonstrating of approaches based on products safe for environment and life. This project aims to release to the market an innovative solution combining a new competitive biopesticide to cultural trainings aiming to reduce land and water pollution through new agricultural practices. SAFWA specific challenges are to meet the requirement of the EU regulation regarding the registration of safe biopesticides and to provide an environment in which agriculture production contributes to reduce the pollution of the water and the land. The main goal of SAFWA is to market a new alternative intended to minimize the risk associated with the use of pesticides. Biopesticides, based on two sporulating (BLB1, LIP) and one non sporulating (S22) Bacillus thuringiensis strains, will be used in the field assays to treat olive, citrus and pomegranate trees as well as tomato to protect these different cultures against five pest species. SAFWA will build on the ongoing European project IPM-4-Citrus achievements both at technological and market assessment levels to drive new cultural practices to farmers in 3 experimental farms around the Mediterranean.

Biotransformation capacities of cells are directly linked to cellular metabolism. The enzymatic process of RNA decay participates to metabolism regulation by controlling gene expression post-transcriptionally. Thousands of RNA molecules belonging to three classes (messenger, ribosomal and transfer RNAs) are prone to be degraded at the same time in cells and compete for enzymes of the degradation machinery. This competition mechanism and the impact of such competition on cell activity have not been previously studied. In the RECOM project, we will characterize for the first time the substrate/enzyme competition mechanism in vivo when thousands different RNAs compete for RNase E binding, the enzyme responsible for the initiation of RNA decay in E. coli. An approach of in vivo enzymology will be developed. Perturbations of the two kinetics partners, the substrates or the enzyme, in the cells using a series of targeted mutants will be performed in vivo and apparent kinetic parameters of RNase E for all RNAs, will be estimated by modelling. By exploring genome-wide RNA stability, the project will challenge the dogma of stable and unstable RNAs. In order to quantify how the RNA competition for decay affects E. coli cell activity, energy and carbon metabolisms will be thoroughly characterized by the measurement of growth, accumulated metabolites and intracellular quantitative multi-omics data. The project will reveal the cellular trade-off for intracellular resource allocation between RNA decay, carbon and energy metabolisms and thus provide the first comprehensive view of bacterial metabolism integrating the interconnections between these three metabolisms. This new vision of the mechanisms governing bacterial life could also open the way to new strategies in biotechnology based on the modulation of RNA decay for cellular activity optimization. The RECOM project deals with the fundamental principles of biochemistry/microbiology. Due to the novelty of the approach, large scientific impacts are expected in the short, medium or long term, in enzymology, bioenergetics, microbial metabolism and modelling. In addition of these scientific impacts in basic and disciplinary research, major economic and social impacts are expected in the longer term due to the identification in the work program of promising strategies for the optimization of bacterial activity for application in biotechnology and synthetic biology.

Given the sixth assessment report of the Intergovernmental Panel on Climate Change (IPCC), the announced depletion of fresh water, the indiscriminate use of toxic chemicals and the impact of all these drifts on the future of our planet and on biodiversity, new production methods of biosourced molecules, less energy-consuming, not generating CO2 and less demanding in fresh water must be investigated to ensure a credible and sustainable transition. In line with these concepts, the EPPIC project proposes to investigate 3 different routes for polymer production starting from sugar by-products or CO2 in sea water. Enzymatic routes with multiples natural or evolved enzymes, cell-based processes involving engineered microorganisms and hybrid processes combining cell-free and cell-based systems will be developed. These innovative production routes will be evaluated using an eco-design and life cycle assessment approach to identify the most promising production routes and to assess their energy and environmental performances.

Replacement of fossils resources by renewable resources is essential to achieve a sustainable growth of human society. Ultimately, energy and carbon used to produce fuels and chemicals must be sourced directly from the Sun and CO2 and synthesized biologically. The CONCEPT project holds the promise by proposing a hybrid strategy, combining both chemical and biological routes, as a hybrid concept of converting CO2 into a value-added product using renewable energy to create an artificial carbon cycle. To achieve this challenge, a unique consortium is being assembled according to the key competences of its partners from different research disciplines needed to establish a novel production basis of complex molecules (more than C1) from CO2. As no single organization or country has the capacity to successfully bring about the innovations and demonstrations intended in CONCEPT on its own, a well-balanced consortium has been arranged, with partners being complementary to each other and willing to closely cooperate in creating a research environment as envisioned in CONCEPT’s ambitious aim. At the moment, 6 legal entities independent from each other (i.e. 4 academics, 2 SMEs) and from 4 different eligible countries (i.e. France, Germany, Spain, Poland) have accepted to be part of the consortium. In the future more legal entities (2 companies, 2 research organisation) from 2 more different countries may join the consortium. Considering that CONCEPT is a pioneer project given the high-risk research due to the novelty of the concept and the huge social, environmental and political implications. Considering the highly competitive funding program in the call H2020-FNR-13-2020: “Bio-based industries leading the way in turning carbon dioxide emissions into chemicals”. The core Consortium headed by Stéphanie Heux and Claire Dumon requests help from the French Research Agency (ANR) to financially support the assembly of this European Scientific Network. In particular, this help will allow: - to strengthen and expand the consortium - to reinforce the project position - to implement actions in order to suppress or reduce identified weaknesses - to organise at three consortium meetings: one for creating the bases for an interdisciplinary and intersectoral collaboration and prepare the first stage submission , the second in order to strengthen the European proposal in view of stage two submission and a third to finalize the second stage proposition. The ambition is to submit a pre-proposal in January 2020 and, if accepted, a full proposal in September 2020. We are strongly convinced that the chances to succeed will be significantly increased with the MRSEI financial support. Also, the CONCEPT‘s concretisation will reinforce the French position in the bio-based manufacturing and processing domain, using biological and renewable raw materials.