During the four-year project, TOPCAPI will
- Use systems biology to optimise the flow of primary metabolites to high-value target compounds. This will result in industry-level improved performance of established actinomycete platforms. Integrating systems biology-driven strain design and state-of-the-art genome editing technology will result in two new host strains optimised for the heterologous expression of pathways of interest.
- Engineer the biosynthesis pathways for the target compounds, informed by metabolic modelling, to obtain high-efficiency synthesis.
- Optimise the expression of the engineered target pathways in preengineered strains to achieve industrially viable production levels of target compounds.
The work of the project is organised over seven Workpackages
The project brings together a multidisciplinary consortium, containing experts in systems biology (University of Manchester and EXPLORA); transcriptome analysis (INBIOTEC) and metabolome analysis of actinomycetes (MEDINA, University of Manchester); unique genome editing techniques and genetic manipulation of actinomycetes (integrase, York; CRISPR/Cas, University of Manchester; S. rimosus, University of Ljubljana) to successfully complete the objectives.
- Work Package One: ‘Omics data collection: fermentation, genome sequence, transcriptomics and metabolomics of reference strains
- Work Package Two: Systems biology analysis and modelling: Omics data analysis and predictive
- Work Package Three: Strain Engineering
- Work Package Four: Iterative systems biology analysis of the new strains
- Work Package Five: Fermentation and validation of the newly engineered strains, TOPCAPI-2A (S. coelicolor) and TOPCAPI-B (S. rimosus)
- Work Package Six: Management
- Work Package Seven: Exploitation and Dissemination
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 720793