Streptomyces has been shown to be an invaluable host for the secretory production of biopharmaceuticals and other heterologous proteins. STREPTOMICS aims to further evaluate this host as a cell factory for the industrial production of proteins of diverse origin including from mammalians, bacteria and archeae of interest for human health and environment. To enhance production, STREPTOMICS will combine genomic data, metabolic network modelling, metabolic flux analysis and proteomics. This systems biology approach will identify genes/proteins with key roles in protein secretion and their interrelationship with cell growth, secretion stress control and energy production/consumption. In addition, some key proteins of the secretion machinery, which may hinder efficient secretion of heterologous proteins, will be investigated. Based on fundamental research of these key proteins to allow rational mutations, also directed evolution, which provides an ideal system to create a protein with optimized properties, in this case for improved secretion, will be performed. Based on the obtained information and modulation, a 'toolbox' of strains will be appropriately engineered and further developed by these state-of-the art approaches such that they optimally over-secrete during fermentation.
Hence, the obtained deliverables will permit the targeted manipulation of specific metabolic pathways and the modulation of key proteins of the protein secretion pathway. As a result of better understanding of the metabolome-secretome interplay strategies for improved protein secretion will be designed. These will combine better energy generation and directed energy consumption for either cell mass production or heterologous protein secretion. Successful realisation of the objectives of the project will therefore provide useful and commercially valuable innovation to the EU Streptomyces protein production platform'.
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