Anti-UV compounds represent a huge market in the cosmetics industry for their capacity to protect humans from sun damages. Unfortunately, current anti-UVs are being criticized for their toxicity towards the endocrine system of human, animals and fishes, and for their allergenicity; replacing them is thus a public health and environment preservation matter. Moreover, being fossil-based, these molecules are very difficult to degrade in the environment and their cost is extremely fluctuant. There is thus a high industrial/societal demand for cutting-edge technologies enabling the production of renewable and safer alternatives. Nevertheless, to achieve this, one must overcome the following major hurdles: (1) availability of natural raw materials at low cost and large volumes, (2) highly selective and efficient (no/limited wastes, high yields and purity), sustainable, safe and cost-effective production process, (3) anti-UVs must exhibit complimentary biological activities as the marketing approval for compounds exhibiting only anti-UV activity is a complex, lengthy and costly procedure, (4) molecules must not exhibit any toxicity for the consumers, and be environmentally friendly, (5) molecules must (i) possess the required physico-chemical properties to be efficiently incorporated in the cosmetic formulation (e.g., hydrophilic-lipophilic balance (HLB)), and (ii) must be photostable for a period of time compatible with the destination of the cosmetic. SINAPUV builds on the pioneer work of Chaire ABI and its partners from Purdue and Warwick universities that demonstrated that naturally occurring sinapoyl malate exhibits promising high anti-UV activity due to a very peculiar mechanism allowing the absorption of all wavelengths within the UV-B range. Unfortunately, sinapoyl malate extraction from plants is not feasible as it is present in very small quantities. SINAPUV is precisely designed to overcome not only this supply issue but also the hurdles described above by proposing a sustainable integrated approach that aims at producing biobased sinapoyl malate analogs directly from sugars and identifying the ones able to advantageously replace criticized commercial anti-UVs. To achieve this ambitious objective, the project relies on the simultaneous investigation of (1) a synthetic biology strategy for the engineering of microorganisms (bacteria and yeast) capable of producing two chemical intermediates - sinapic acid and sinapoyl malate - from carbohydrates, (2) the development of an integrated microbial production using the engineered strains and agro-industrial byproducts as fermentation medium, and purification processes allowing the production intensification of the intermediates, (3) the development of sustainable (chemo-)enzymatic pathways to sinapoyl malate analogs with tunable HLB from the previous intermediates, (3) the study of their spectral/biological properties both at the molecular and at the formulation level, (4) the determination of the toxicity of the most promising analogs, and (5) a life cycle assessment allowing the most durable analogs and integrated process(es) to be identified. Finally, the analogs exhibiting the highest anti-UV/biological activities and the lowest toxicity will be validated as proof of concept before their industrialization. To rise to this challenge, academic actors and industrials have decided to build a private public partnership gathering all the scientific and industrial expertise required to fully address this multidisciplinary project. Internationally recognized French academic laboratories in synthetic biology (MICALIS), fermentation/downstream processing/green chemistry/LCA (Chaire ABI), and endocrine disruption (HSC) will work hand in hand with a start-up specialized in the construction of industry compliant genetically engineered micro-organisms (Abolis) and a world-leading company specialized in the production of biobased cosmetic ingredients (Givaudan Active Beauty).

I-CHEM’ALGAE (“Challenge 5 - Sécurité Alimentaire et Défi Démographique Ressources biologiques, exploitation durable des écosystèmes et Bioéconomie”; axe 6 - Bioéconomie: technologies spécifiques et approches système.”) aims to develop an original integrated strategy to optimize microalgae biorefinery, based on metabolomics (by using chemometric tools to merge multimodal and multiscale spectroscopic data sets) and process engineering (including cultivation in photobioreactors, deconstruction/fractionation aspects). This strategy will address the technological issues related to chemotyping/dereplication of microalgae and cell resistance to develop an optimized and intensified biorefinery approach for microalgae entire valorisation. Indeed, even if microalgae are mainly known for their potential in biofuel production, they could represent innovative and biologically promising resources for high added value sectors such as cosmetics, provided that efficient tools are available for their chemical characterization. This collaborative project, involves three academic and one industrial partners, the latter being specialized in the development and production of cosmetic ingredients. This project will thus exploit the synergy between process engineering, analytical, chemoinformatic and phyto-chemistry skills with those of a major player in the development of blue biotechnology in the cosmetic field (Givaudan) in order to meet the scientific and technological objectives while taking into account environmental and industrial concerns (solvent selection and time requirement of the global workflow). Thus the PRCE financing tool is clearly consistent with the objectives of this project. Beside a coordination task, the scientific and technical program of i-Chem’Algae is organized in 4 main tasks developed over 36 months. The innovative nature is reflected by the global project structure that aims to provide an integrated approach for microalgae biorefinery, but also within the three technical tasks. Task 1 aims to develop a chemical and micro-mechanical pattern recognition model for microalgae screening according to the global nature of their chemical composition and cell resistance, these two aspects being of primary importance for both biorefinery engineering and valorisation. The main novelty consists in the fusion of multi-modal and multi-scale non-invasive spectroscopy data stets recorded on entire cell to build the pattern recognition model. The objective of task 2 is to develop a procedure for microalgae biomass deconstruction and fractionation guided by the Task 1 results and to produce chemically simplified extracts, which will be further submitted to a fine chemical profiling (Task 3). Task 2 also includes cultivation under photobioreactor control in order to allow a continuous state biomass production. The objective of Task 3 is to develop procedure for the chemical characterization of small metabolites mainly based on dereplication, Nuclear Magnetic Resonance, chemometric tools and databasing and to connect these data with biological activities. Moreover, a combination of original tools such as LC-NMR and artificial intelligence will be implemented to speed up the de novo structure elucidation process in case of novel compounds. Finally, Task 4, aims to provide a technical and economic evaluation of the proposed integrated strategy for the development of microalgae-based new cosmetic ingredients. I-Chem'Algae is thus a research project with 3 kinds of final deliverables including knowledge acquisition by developing an original strategy for microalgae biorefinery - this integrated approach being transferable on other starting materials -, societal aspects with new concepts for the use of alternative raw materials (here microalgae) compatible with the concepts of circular economy and the use of sustainable processes and finally industrial developments by the development of original microalgae-derived cosmetic active ingredients.