Abstract
Streptomyces coelicolor is the most intensively studied and a model member of the genus Streptomyces, and the number of genes encoded in its genome is among the highest of any bacterium known to date [1]. During cultivation, a culture of S. coelicolor undergoes a comprehensive metabolic rearrangement in response to environmental changes (e.g. nutrient limitation), leading to a transition from growth to secondary metabolite production phase. This transition is assumed to be controlled by a complex regulatory network rather than by individual global regulators [2]. The SysMO (STREAM) project heads for a detailed molecular understanding and characterization of this regulatory network by a systems biology approach involving combination of full-scale ‘omics analysis of high time-resolution samplings, and mathematical modelling.To ensure the required degree of reproducibility in batch cultivations of S. coelicolor, suitable media and cultivation conditions were developed along with a set of methods for closely monitoring fermentation and culture growth parameters, nutrient and secondary metabolite production levels. Several full-scale time-series sampling experiments involving different strains and media conditions have been performed so far, yielding material for ‘omics data generation and subsequent modelling attempts. From the first transcriptome analyses using a new custom-designed Affymetrix microarray, we were able to precisely profile expression changes and allocate them to specific time points of cultivation, thereby re-constructing the series of major expression changes of gene clusters in response to the phosphate depletion event during cultivation. From these data, we find that the metabolic switch actually consists of multiple finely orchestrated switching events starting already many hours before the classically defined transition phase. The main switch in gene expression occurs within only two hours, with changes in antibiotic biosynthesis genes being delayed