The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to develop a platform of “green” chemoenzymatic methods for the production of high value active pharmaceutical ingredients – both those currently on the market, and those in development pipelines of the Pharma industry. The partners will exemplify the use of the platform through its application in the production of 4 drugs currently on the market – namely Duloxetine, Atomexetine, Ramosetron and Paricalcitol. In order to achieve this objective the proposal brings together 3 partners with complementary skills: Kelada Pharmachem: Phase transfer catalysis/organo catalysis/scale-up of chemical processes Cerbios Pharma: Biocatalysis and fermentation methodologies for drug production IC-CNR: Protein crystallography and enzymatic engineering

The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to develop three new categories of quaternary ammonium salts to be used as catalysts for the cost-efficient and green manufacture of high value active pharmaceutical ingredients. In order to achieve this objective the proposal brings together 3 partners with complementary skills: University of Naples(UNIN): experts in the preparation and purification of cyclic peptides. Experts in solid phase synthesis and immobilisation of peptides on solid support. KelAda Pharmachem: Phase transfer catalysis/organo catalysis/scale-up of chemical processes University of Linz(JKU Linz): experts in design of new ammonium salts and optimisation of enantioselective phase transfer catalyses. We have broken this proposal into the following separate Work Packages: WP1. Preparation of new designer ammonium salts [WP leader: Kelada] WP2. Preparation of cyclic peptide based ammonium salts [WP leader: UNINA] WP3. Evaluation of new ammonium salt catalysts prepared through WP1 [WP JKULinz] WP4. Evaluation of new Ammonium salt catalysts prepared through WP2[WP leader: UNINA] WP5. Application of Ammonium salts to drug production [WP leader: Kelada] WP6. Scale up of key steps or the manufacture of drugs [WP leader: Kelada] WP 7. Management, Communication & Dissemination [WP leader: KelAda] The above WP’s will be undertaken via a series of interlinked secondment of researchers between consortium partners and will be complemented by a series of training and other initiatives to facilitate interdisciplinary and intersectoral knowledge sharing and exchange.

The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to develop and exemplify the use of new catalysts and new green reactions to manufacture important halogenated compounds that could be used in drug discovery and drug production. In order to achieve this objective the proposal brings together 3 partners with complementary skills: University of Naples (UNINA): expertise in medicinal chemistry and drug discovery. KelAda Pharmachem: expertise in green chemistry, chemical batch process development and scale-up. UCO: expertise in process engineering of continuous flow processes. We have broken this proposal into the following separate technical Work Packages: WP1: Preparation of new catalysts for efficient desymmetrization [WP Leader: UNINA]. WP2: Development of enantiospecific halogenation including Fluorination. [WP Leader: Kelada Pharmachem]. WP3 Drug Candidate, library creation & in vitro testing. [WP Leader: Kelada Pharmachem] WP4 Development of flow variant and scale-up.[WP Leader: UCO} The above WP's will be undertaken via a series of interlinked secondment of researchers between the consortium partners and will be complemented by a series of training and other initiatives to facilitate interdisciplinary and inter-sectoral knowledge sharing and exchange.

The aim of this project is to bring together subject matter experts from the academic and non-academic sectors to establish proof-of-concept of the utility of a new platform for fast and general elucidation of the interaction between proteins and RNA. The development of analytical methods for identification of RNA-binding proteins (RPBs) and their corresponding RNA motifs, will permit and accelerate: i) a deeper understanding of the roles of gene regulation and protein expression; ii) development of personalised medicines via regulation of protein expression; and iii) rapid identification of proteomes involved in specific diseases. In doing so, this project will have outputs which have significant market opportunities and societal benefits, including, but not limited to, stimulating job creation in the pharmabiotech and diagnostics sectors and reducing costs for national and EU healthcare budgets.

Global terrestrial plant biodiversity remains a largely untapped source of natural bioactive compounds. In fact, valid sources are even “hiding in plain sight”, yet not “within reach” due to lack of effective technical solutions to unlock their potential. In this context, the PROSPLIGN consortium has developed an innovative bioprospecting approach that uses cutting-edge and complementary chemical and enzymatic methods, supported by statistical analysis and coupled with high-throughput detection methods, to enable the discovery of bioactive molecules from lignin, one of the fractions of the most abundant biopolymer on Earth (lignocellulose). Lignin “chemical biodiversity” will enable PROSPLIGN to cover three target markets (pharmaceuticals, cosmetics and fragrances) with a combined market of >€1.4 trillion. The project will use lignin derived from 9 different species and investigate at least 3 different chemical approaches and 10 different enzymes to obtain up to 1000 mixtures of lignin-derived compounds, and then pass a progressively narrower “hit validation funnel” in industrially relevant environments, being screened via up to 17 different bioactivity assays. Sustainable production routes for at least 2 of the most promising compounds per sector, directly or following derivatisation, will be proposed. Compared to traditional approaches, PROSPLIGN's bioprospecting avoids animal cruelty, expensive exploration efforts (no novel animal/plants discovery), disruptive extractions (seeking “hidden gems” in an abundant but underexploited “biomass mine”), and directly targets the liberation of readily testable bio/chemical-functionality present in plant material, superior to other approaches relying on “manipulation-intensive” microbial strain culture or “extrapolation” from DNA/RNA). Ultimately, PROSPLIGN will contribute to a new generation of biobased bioactives, unlocking more value from existing sources whose immense potential has yet to be harnessed.