Streptomics will materialize its goals through a multidisciplinary intertwined approach with 9 work packages situated at different levels. At the strain engineering platform recombinant strains will be constructed for different purposes. In WP1 it is aimed to clone in suitable Streptomyces expression/secretion vectors a selected panel of industrially and biopharmaceutically proteins of relevance for the industrial partners (Direvo, Prokaria, GSK) and with a wide range of biological characteristics. Using the analytical platform, expression profiles of genes and proteins during the secretion process of heterologous proteins secreted with different efficiency and under different fermentation regimes (WP8), will be identified. Influence of heterologous protein secretion and the stress it provokes as such activating transcriptional networks will be identified by transcriptomic analysis obtained with the aid of DNA microarrays (WP5). Since proteins represent the actual functional molecules in the cell, the proteomic data obtained from the 2D analysis and the for S. lividans newly introduced multidimensial, nano-LC/MS approach (WP6) will identify which proteins are actually up- or down regulated during the secretion and fermentation process. In this manner insight in links between transcription, translation and post-translation modification will be gained. Based on these results genes will be assigned that might influence overproduction of heterologous proteins. Mutation of these genes (WP2) could dramatically influence heterologous protein secretion and/or cell growth. Combining measurement of the Metabolome with Metabolic Flux Analysis (WP4) using Bioinformatics (WP7) will facilitate construction of a genome-scale model of S. lividans. This model will together with profiles of enzyme activities and flux measurement provide suggestions for further rational strain engineering (WP2), e.g. through deletion or overexpression of metabolic pathway by engineering specific steps in glucose catabolism and/or amino acid biosynthesis.