Metabolic switching in Streptomyces coelicolor Timeseries 1

Background: During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples. Results: Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis. Conclusions: Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting. Keywords: time course F199: 32 samples, no replicates; one hour resolution from 20-44h; two hour resolution 44-60h; sample missing for 25h F201: 8 samples, no replicates; four hour resolution from 24-48h; one sample at 60h F202: 15 samples, no replicates; four hour resolution from 24-32h; one hour resolution from 34-40h; two hour resolution from 42-48h; one sample at 60h SysMO STREAM Consortium