Global analysis of growth phase responsive gene expression and regulation of antibiotic biosynthetic pathways in Streptomyces coelicolor using DNA microarrays

The eubacterial species Streptomyces coelicolor proceeds through a complex growth cycle in which morphological differentiation/development is associat ed with a transition from primary to secondary metabolism and the productio n of antibiotics. We used DNA microarrays and mutational analysis to invest igate the expression of individual genes and multigene antibiotic biosynthe tic pathways during these events. We identified expression patterns in bios ynthetic, regulatory, and ribosomal protein genes that were associated high ly specifically with particular stages of development. A knowledge-based al gorithm that correlates temporal changes in expression with chromosomal pos ition identified groups of contiguous genes expressed at discrete stages of morphological development, inferred the boundaries of known antibiotic syn thesis gene loci, and revealed novel physical clusters of coordinately regu lated genes. Microarray analysis of RNA from cells mutated in genes regulat ing synthesis of the antibiotics actinorhodin (Act) and undecylprodigiosin (Red) identified proximate and distant sites that contain putative ABC tran sporter and two-component system genes expressed coordinately with genes of specific biosynthetic pathways and indicated the existence of two function ally and physically discrete regulons in the Red pathway.