Objective TOPCAPI will exploit the natural fabrication power of actinomycetes as microbial cell factories to produce three high value compounds: GE2270, a starter compound for the semi-synthesis of NAI-Acne, a new topical anti-acne drug in Phase II clinical trials; 6-desmethyl-tetracycline (6DM-TC) and 6-desmethyl 6-deshydro tetracycline (6DM6DH-TC), intermediates for semi-synthetic conversion to medically important type II polyketide tetracyclines (TC), e.g. minocycline, tigecycline, and the novel omadacycline, which is in Phase III clinical trials, to be used against Methicillin-resistant Staphylococcus aureus infections. Our work will focus on two bacterial host species: Streptomyces coelicolor and Streptomyces rimosus. These host species will be characterised using systems biology approaches, applying integrated data analysis to transcriptomics and metabolomics experiments, combined with predictive mathematical modelling to drive the rapid improvement of these microbial cell factories for industrial drug production using advanced metabolic and biosynthetic engineering approaches. At the same time, we will establish an expanded toolbox for the engineering of actinomycete bacteria as cell factories for other high added-value compounds.In the proposed 4-year project, we will: 1. Host engineer two new actinomycete strains for industry-level improved heterologous compound production through integrating systems biology-driven strain design and state-of-the-art genome editing. 2. Engineer the biosynthesis pathways to obtain high-efficiency synthesis of GE2270 and new pathway variants for 6DM-TC and 6DM6DH-TC as well as improve its production purity.3. Optimise the expression of the engineered target pathways in pre-engineered strains to achieve industrially viable production levels of ≈1 g/L for GE2270 and ≈24 g/L for 6DM-TC, while creating a complete novel production strain for 6DM6DH-TC. Fields of science natural sciencescomputer and information sciencesdata scienceengineering and technologyindustrial biotechnologymetabolic engineeringnatural sciencesbiological sciencesmicrobiologybacteriologymedical and health sciencesbasic medicinepharmacology and pharmacy Keywords actinomycete chassis engineering NRPS Type II PKS pharmaceuticals systems biology Programme(s) H2020-EU.2.1.4. - INDUSTRIAL LEADERSHIP - Leadership in enabling and industrial technologies – Biotechnology Main Programme Topic(s) BIOTEC-03-2016 - Microbial chassis platforms with optimized metabolic pathways for industrial innovations through systems biology Call for proposal H2020-NMBP-2016-2017 See other projects for this call Sub call H2020-NMBP-BIO-2016 Funding Scheme RIA - Research and Innovation action Coordinator THE UNIVERSITY OF MANCHESTER Net EU contribution € 1 554 128,75 Address Oxford road M13 9PL Manchester United Kingdom See on map Region North West (England) Greater Manchester Manchester Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Participants (7) Sort alphabetically Sort by Net EU contribution Expand all Collapse all ASOCIACION DE INVESTIGACION INBIOTEC, INSTITUTO DE BIOTECHNOLOGIA DE LEON Spain Net EU contribution € 509 842,50 Address Avenida real 1 parque cientifico 24006 Leon See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Centro (ES) Castilla y León León Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 FUNDACION CENTRO DE EXCELENCIA EN INVESTIGACION DE MEDICAMENTOS INNOVADORES EN ANDALUCIA Spain Net EU contribution € 499 375,00 Address Avda del conocimiento 3 18100 Armilla granada See on map Region Sur Andalucía Granada Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERZA V LJUBLJANI Slovenia Net EU contribution € 449 425,00 Address Kongresni trg 12 1000 Ljubljana See on map Region Slovenija Zahodna Slovenija Osrednjeslovenska Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 UNIVERSITY OF YORK United Kingdom Net EU contribution € 531 967,50 Address Heslington YO10 5DD York north yorkshire See on map Region Yorkshire and the Humber North Yorkshire York Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 EXPLORA SRL Italy Net EU contribution € 424 372,50 Address Via giacomo peroni 386 00131 Roma See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Centro (IT) Lazio Roma Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 NAICONS SRL Italy Net EU contribution € 535 000,00 Address Via guaragna 3 20147 Saronno va See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 ACIES BIO BIOTEHNOLOSKE RAZISKAVE IN RAZVOJ DOO Slovenia Net EU contribution € 559 250,00 Address Tehnoloski park 21 1000 Ljubljana See on map SME The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed. Yes Region Slovenija Zahodna Slovenija Osrednjeslovenska Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
